A Peptide Targeting Inflammatory CNS Lesions in the EAE Rat Model of Multiple Sclerosis.

PubMed

Boiziau, Claudine; Nikolski, Macha; Mordelet, Elodie; Aussudre, Justine; Vargas-Sanchez, Karina; Petry, Klaus G

2018-06-01

Multiple sclerosis is characterized by inflammatory lesions dispersed throughout the central nervous system (CNS) leading to severe neurological handicap. Demyelination, axonal damage, and blood brain barrier alterations are hallmarks of this pathology, whose precise processes are not fully understood. In the experimental autoimmune encephalomyelitis (EAE) rat model that mimics many features of human multiple sclerosis, the phage display strategy was applied to select peptide ligands targeting inflammatory sites in CNS. Due to the large diversity of sequences after phage display selection, a bioinformatics procedure called "PepTeam" designed to identify peptides mimicking naturally occurring proteins was used, with the goal to predict peptides that were not background noise. We identified a circular peptide CLSTASNSC called "Ph48" as an efficient binder of inflammatory regions of EAE CNS sections including small inflammatory lesions of both white and gray matter. Tested on human brain endothelial cells hCMEC/D3, Ph48 was able to bind efficiently when these cells were activated with IL1β to mimic inflammatory conditions. The peptide is therefore a candidate for further analyses of the molecular alterations in inflammatory lesions.

Development of a method for urine bikunin/urinary trypsin inhibitor (UTI) quantitation and structural characterization: Application to type 1 and type 2 diabetes.

PubMed

Lepedda, Antonio Junior; Nieddu, Gabriele; Rocchiccioli, Silvia; Fresu, Pietro; De Muro, Pierina; Formato, Marilena

2013-12-01

Bikunin is a plasma proteinase inhibitor often associated with inflammatory conditions. It has a half-life of few minutes and it is rapidly excreted into urine as urinary trypsin inhibitor (UTI). UTI levels are usually low in healthy individuals but they can increase up to tenfold in both acute and chronic inflammatory diseases. This article describes a sensitive method for both direct UTI quantitation and structural characterization. UTI purification was performed by anion exchange micro-chromatography followed by SDS-PAGE. A calibration curve for protein quantitation was set up by using a purified UTI fraction. UTI identification and structural characterization was performed by Nano-LC-MS/MS analysis. The method was applied on urine samples from 9 patients with type 1 diabetes, 11 patients with type 2 diabetes, and 28 healthy controls, matched for age and sex with patients, evidencing higher UTI levels in both groups of patients with respect to controls (p < 0.001 and p = 0.001, respectively). Spearman's correlation tests highlighted no association between UTI levels and age in each group tested. Owing to the elevated sensitivity and specificity, the described method allows UTI quantitation from very low quantities of specimen. Furthermore, as UTI concentration is normalized for creatinine level, the analysis could be also performed on randomly collected urine samples. Finally, MS/MS analysis prospects the possibility of characterizing PTM sites potentially able to affect UTI localization, function, and pathophysiological activity. Preliminary results suggest that UTI levels could represent a useful marker of chronic inflammatory condition in type 1 and 2 diabetes. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

TUNING IMMUNE TOLERANCE WITH VASOACTIVE INTESTINAL PEPTIDE: A NEW THERAPEUTIC APPROACH FOR IMMUNE DISORDERS

PubMed Central

POZO, DAVID; GONZALEZ-REY, ELENA; CHORNY, ALEJO; ANDERSON, PER; VARELA, NIEVES; DELGADO, MARIO

2007-01-01

The induction of immune tolerance is essential for the maintenance of immune homeostasis and to limit the occurrence of exacerbated inflammatory and autoimmune conditions. Multiple mechanisms act together to ensure self-tolerance, including central clonal deletion, cytokine deviation and induction of regulatory T cells. Identifying the factors that regulate these processes is crucial for the development of new therapies of autoimmune diseases and transplantation. The vasoactive intestinal peptide (VIP) is a well-characterized endogenous anti-inflammatory neuropeptide with therapeutic potential for a variety of immune disorders. Here we examine the latest research findings, which indicate that VIP participates in maintaining immune tolerance in two distinct ways: by regulating the balance between pro-inflammatory and anti-inflammatory factors, and by inducing the emergence of regulatory T cells with suppressive activity against autoreactive T-cell effectors. PMID:17521775

Time-Course of Changes in Inflammatory Response after Whole-Body Cryotherapy Multi Exposures following Severe Exercise

PubMed Central

Pournot, Hervé; Bieuzen, François; Louis, Julien; Fillard, Jean-Robert; Barbiche, Etienne; Hausswirth, Christophe

2011-01-01

The objectives of the present investigation was to analyze the effect of two different recovery modalities on classical markers of exercise-induced muscle damage (EIMD) and inflammation obtained after a simulated trail running race. Endurance trained males (n = 11) completed two experimental trials separated by 1 month in a randomized crossover design; one trial involved passive recovery (PAS), the other a specific whole body cryotherapy (WBC) for 96 h post-exercise (repeated each day). For each trial, subjects performed a 48 min running treadmill exercise followed by PAS or WBC. The Interleukin (IL) -1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha (TNF-α), protein C-reactive (CRP) and white blood cells count were measured at rest, immediately post-exercise, and at 24, 48, 72, 96 h in post-exercise recovery. A significant time effect was observed to characterize an inflammatory state (Pre vs. Post) following the exercise bout in all conditions (p<0.05). Indeed, IL-1β (Post 1 h) and CRP (Post 24 h) levels decreased and IL-1ra (Post 1 h) increased following WBC when compared to PAS. In WBC condition (p<0.05), TNF-α, IL-10 and IL-6 remain unchanged compared to PAS condition. Overall, the results indicated that the WBC was effective in reducing the inflammatory process. These results may be explained by vasoconstriction at muscular level, and both the decrease in cytokines activity pro-inflammatory, and increase in cytokines anti-inflammatory. PMID:21829501

Time-course of changes in inflammatory response after whole-body cryotherapy multi exposures following severe exercise.

PubMed

Pournot, Hervé; Bieuzen, François; Louis, Julien; Mounier, Rémi; Fillard, Jean-Robert; Barbiche, Etienne; Hausswirth, Christophe

2011-01-01

The objectives of the present investigation was to analyze the effect of two different recovery modalities on classical markers of exercise-induced muscle damage (EIMD) and inflammation obtained after a simulated trail running race. Endurance trained males (n = 11) completed two experimental trials separated by 1 month in a randomized crossover design; one trial involved passive recovery (PAS), the other a specific whole body cryotherapy (WBC) for 96 h post-exercise (repeated each day). For each trial, subjects performed a 48 min running treadmill exercise followed by PAS or WBC. The Interleukin (IL) -1 (IL-1), IL-6, IL-10, tumor necrosis factor alpha (TNF-α), protein C-reactive (CRP) and white blood cells count were measured at rest, immediately post-exercise, and at 24, 48, 72, 96 h in post-exercise recovery. A significant time effect was observed to characterize an inflammatory state (Pre vs. Post) following the exercise bout in all conditions (p<0.05). Indeed, IL-1β (Post 1 h) and CRP (Post 24 h) levels decreased and IL-1ra (Post 1 h) increased following WBC when compared to PAS. In WBC condition (p<0.05), TNF-α, IL-10 and IL-6 remain unchanged compared to PAS condition. Overall, the results indicated that the WBC was effective in reducing the inflammatory process. These results may be explained by vasoconstriction at muscular level, and both the decrease in cytokines activity pro-inflammatory, and increase in cytokines anti-inflammatory.

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease.

PubMed

Godlewska, Urszula; Brzoza, Piotr; Sroka, Aneta; Majewski, Pawel; Jentsch, Holger; Eckert, Martin; Eick, Sigrun; Potempa, Jan; Zabel, Brian A; Cichy, Joanna

2017-01-01

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity.

Human immune cells' behavior and survival under bioenergetically restricted conditions in an in vitro fracture hematoma model

PubMed Central

Hoff, Paula; Maschmeyer, Patrick; Gaber, Timo; Schütze, Tabea; Raue, Tobias; Schmidt-Bleek, Katharina; Dziurla, René; Schellmann, Saskia; Lohanatha, Ferenz Leonard; Röhner, Eric; Ode, Andrea; Burmester, Gerd-Rüdiger; Duda, Georg N; Perka, Carsten; Buttgereit, Frank

2013-01-01

The initial inflammatory phase of bone fracture healing represents a critical step for the outcome of the healing process. However, both the mechanisms initiating this inflammatory phase and the function of immune cells present at the fracture site are poorly understood. In order to study the early events within a fracture hematoma, we established an in vitro fracture hematoma model: we cultured hematomas forming during an osteotomy (artificial bone fracture) of the femur during total hip arthroplasty (THA) in vitro under bioenergetically controlled conditions. This model allowed us to monitor immune cell populations, cell survival and cytokine expression during the early phase following a fracture. Moreover, this model enabled us to change the bioenergetical conditions in order to mimic the in vivo situation, which is assumed to be characterized by hypoxia and restricted amounts of nutrients. Using this model, we found that immune cells adapt to hypoxia via the expression of angiogenic factors, chemoattractants and pro-inflammatory molecules. In addition, combined restriction of oxygen and nutrient supply enhanced the selective survival of lymphocytes in comparison with that of myeloid derived cells (i.e., neutrophils). Of note, non-restricted bioenergetical conditions did not show any similar effects regarding cytokine expression and/or different survival rates of immune cell subsets. In conclusion, we found that the bioenergetical conditions are among the crucial factors inducing the initial inflammatory phase of fracture healing and are thus a critical step for influencing survival and function of immune cells in the early fracture hematoma. PMID:23396474

A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease.

PubMed

Farzaei, Mohammad Hosein; Bahramsoltani, Roodabeh; Abdolghaffari, Amir Hossein; Sodagari, Hamid Reza; Esfahani, Shadi A; Rezaei, Nima

2016-06-01

Inflammatory bowel disease (IBD) is a recurrent idiopathic inflammatory condition, characterized by disruption of the gut mucosal barrier. This mechanistic review aims to highlight the significance of plant-derived natural compounds as dietary supplements, which can be used in addition to restricted conventional options for the prevention of IBD and induction of remission. Various clinical trials confirmed the effectiveness and tolerability of natural supplements in patients with IBD. Mounting evidence suggests that these natural compounds perform their protective and therapeutic effect on IBD through numerous molecular mechanisms, including anti-inflammatory and immunoregulatory, anti-oxidative stress, modulation of intracellular signaling transduction pathways, as well as improving gut microbiota. In conclusion, natural products can be considered as dietary supplements with therapeutic potential for IBD, provided that their safety and efficacy is confirmed in future well-designed clinical trials with adequate sample size.

Inflammation--a lifelong companion. Attempt at a non-analytical holistic view.

PubMed

Ferencík, M; Stvrtinová, V; Hulín, I; Novák, M

2007-01-01

Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.

Molecular mechanism of action of Pelargonidin-3-O-glucoside, the main anthocyanin responsible for the anti-inflammatory effect of strawberry fruits.

PubMed

Duarte, Larissa Jeremias; Chaves, Vitor Clasen; Nascimento, Marcus Vinicius Pereira Dos Santos; Calvete, Eunice; Li, Mingchuan; Ciraolo, Elisa; Ghigo, Alessandra; Hirsch, Emilio; Simões, Claudia Maria Oliveira; Reginatto, Flávio Henrique; Dalmarco, Eduardo M

2018-05-01

Fragaria x ananassa Duch., popularly called strawberry, is known for its worldwide consumption and important biological activities, and these effects are related to its high concentration of anthocyanins. Pelargonidin-3-O-glucoside (P3G) is a major anthocyanin found in strawberry, and was evaluated for its anti-inflammatory action in experimental models. The effect of strawberry extract and P3G, on leukocyte migration, exudation levels and many inflammatory mediators, was therefore evaluated in an in vivo model. An in vitro study was also carried out to characterize the effect of P3G on mitogen-activated protein kinases, and on nuclear transcript factors NF-κB and AP-1. The results revealed that the strawberry and P3G have important anti-inflammatory proprieties, and the anti-inflammatory mechanism of P3G involves the arrest of IkB-α activation and reduction in JNK MAPK phosphorylation. The results reinforce that strawberry fruits are functional foods that can act as an adjuvant in the treatment of inflammatory conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Endogenous Acetylcholine Controls the Severity of Polymicrobial Sepsisassociated Inflammatory Response in Mice.

PubMed

Amaral, Flávio Almeida; Fagundes, Caio Tavares; Miranda, Aline Silva; Costa, Vivian Vasconceios; Resende, Livia; Gloria de Souza, Danielle da; Prado, Vania Ferreira; Teixeira, Mauro Martins; Maximo Prado, Marco Antonio; Teixeira, Antonio Lucio

2016-01-01

Acetylcholine (ACh) is the main mediator associated with the anti-inflammatory cholinergic pathway. ACh plays an inhibitory role in several inflammatory conditions. Sepsis is a severe clinical syndrome characterized by bacterial dissemination and overproduction of inflammatory mediators. The aim of the current study was to investigate the participation of endogenous ACh in the modulation of inflammatory response induced by a model of polymicrobial sepsis. Wild type (WT) and vesicular acetylcholine transporter knockdown (VAChT(KD)) mice were exposed to cecal ligation and perforation- induced sepsis. Levels of Tumor Necrosis Factor Alpha (TNF-α) and bacterial growth in peritoneal cavity and serum, and neutrophil recruitment into peritoneal cavity were assessed. The concentration of TNF-α in both compartments was higher in VAChT(KD) in comparison with WT mice. VAChT(KD) mice presented elevated burden of bacteria in peritoneum and blood, and impairment of neutrophil migration to peritoneal cavity. This phenotype was reversed by treatment with nicotine salt. These findings suggest that endogenous ACh plays a major role in the control of sepsis-associated inflammatory response.

Brainstem encephalitis: etiologies, treatment, and predictors of outcome

PubMed Central

Tan, Ik Lin; Mowry, Ellen M.; Steele, Sonya U.; Pardo, Carlos A.; McArthur, Justin C.; Nath, Avindra

2016-01-01

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy. PMID:23749332

The beneficial role of anti-inflammatory dietary ingredients in attenuating markers of chronic low-grade inflammation in aging.

PubMed

Panickar, Kiran S; Jewell, Dennis E

2015-08-01

Aging in humans is associated with chronic low-grade inflammation (systemic), and this condition is sometimes referred to as "inflammaging". In general, canines also age similarly to humans, and such aging is associated with a decline in mobility, joint problems, weakened muscles and bones, reduced lean body mass, cancer, increased dermatological problems, decline in cognitive ability, reduced energy, decreased immune function, decreased renal function, and urinary incontinence. Each of these conditions is also associated with an increase in pro-inflammatory cytokines. An inflammatory state characterized by an increase in pro-inflammatory markers including but not restricted to tumor necrosis factor-α, interleukin-6, IL-1β, and C-reactive protein (CRP) is believed to contribute to or worsen a general decline in biological mechanisms responsible for physical function with aging. Nutritional management of inflammation in aging dogs is important in maintaining health. In particular, natural botanicals have bioactive components that appear to have robust anti-inflammatory effects and, when included in the diet, may contribute to a reduction in inflammation. While there are scientific data to support the anti-inflammatory effects and the efficacy of such bioactive molecules from botanicals, the clinical data are limited and more studies are needed to validate the efficacy of these ingredients. This review will summarize the role of dietary ingredients in reducing inflammatory molecules as well as review the evidence available to support the role of diet and nutrition in reducing chronic low-grade systemic inflammation in animal and human studies with a special reference to canines, where possible.

Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).

PubMed

Ojeda-Ojeda, Miriam; Murri, Mora; Insenser, María; Escobar-Morreale, Héctor F

2013-01-01

Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.

Biopharmaceutical considerations and characterizations in development of colon targeted dosage forms for inflammatory bowel disease.

PubMed

Malayandi, Rajkumar; Kondamudi, Phani Krishna; Ruby, P K; Aggarwal, Deepika

2014-04-01

Colon targeted dosage forms have been extensively studied for the localized treatment of inflammatory bowel disease. These dosage forms not only improve the therapeutic efficacy but also reduce the incidence of adverse drug reactions and hence improve the patient compliance. However, complex and highly variable gastro intestinal physiology limits the clinical success of these dosage forms. Biopharmaceutical characteristics of these dosage forms play a key role in rapid formulation development and ensure the clinical success. The complexity in product development and clinical success of colon targeted dosage forms are based on the biopharmaceutical characteristics such as physicochemical properties of drug substances, pharmaceutical characteristics of dosage form, physiological conditions and pharmacokinetic properties of drug substances as well as drug products. Various in vitro and in vivo techniques have been employed in past to characterize the biopharmaceutical properties of colon targeted dosage forms. This review focuses on the factors influencing the biopharmaceutical performances of the dosage forms, in vitro characterization techniques and in vivo studies.

Different molecular signatures in magnetic resonance imaging-staged facioscapulohumeral muscular dystrophy muscles.

PubMed

Tasca, Giorgio; Pescatori, Mario; Monforte, Mauro; Mirabella, Massimiliano; Iannaccone, Elisabetta; Frusciante, Roberto; Cubeddu, Tiziana; Laschena, Francesco; Ottaviani, Pierfrancesco; Ricci, Enzo

2012-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies and is characterized by a non-conventional genetic mechanism activated by pathogenic D4Z4 repeat contractions. By muscle Magnetic Resonance Imaging (MRI) we observed that T2-short tau inversion recovery (T2-STIR) sequences identify two different conditions in which each muscle can be found before the irreversible dystrophic alteration, marked as T1-weighted sequence hyperintensity, takes place. We studied these conditions in order to obtain further information on the molecular mechanisms involved in the selective wasting of single muscles or muscle groups in this disease. Histopathology, gene expression profiling and real time PCR were performed on biopsies from FSHD muscles with different MRI pattern (T1-weighted normal/T2-STIR normal and T1-weighted normal/T2-STIR hyperintense). Data were compared with those from inflammatory myopathies, dysferlinopathies and normal controls. In order to validate obtained results, two additional FSHD samples with different MRI pattern were analyzed. Myopathic and inflammatory changes characterized T2-STIR hyperintense FSHD muscles, at variance with T2-STIR normal muscles. These two states could be easily distinguished from each other by their transcriptional profile. The comparison between T2-STIR hyperintense FSHD muscles and inflammatory myopathy muscles showed peculiar changes, although many alterations were shared among these conditions. At the single muscle level, different stages of the disease correspond to the two MRI patterns. T2-STIR hyperintense FSHD muscles are more similar to inflammatory myopathies than to T2-STIR normal FSHD muscles or other muscular dystrophies, and share with them upregulation of genes involved in innate and adaptive immunity. Our data suggest that selective inflammation, together with perturbation in biological processes such as neoangiogenesis, lipid metabolism and adipokine production, may contribute to the sequential bursts of muscle degeneration that involve individual muscles in an asynchronous manner in this disease.

Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.

PubMed

Algieri, Francesca; Rodriguez-Nogales, Alba; Vezza, Teresa; Garrido-Mesa, Jose; Garrido-Mesa, Natividad; Utrilla, M Pilar; González-Tejero, M Reyes; Casares-Porcel, Manuel; Molero-Mesa, Joaquin; Del Mar Contreras, Maria; Segura-Carretero, Antonio; Pérez-Palacio, José; Diaz, Caridad; Vergara, Noemí; Vicente, Francisca; Rodriguez-Cabezas, M Elena; Galvez, Julio

2016-08-22

Plants from genus Lavandula have been used as anti-inflammatory drugs in Mediterranean traditional medicine. Nowadays, there is a growing interest for complementary medicine, including herbal remedies, to treat inflammatory bowel disease (IBD). To test the anti-inflammatory properties of Lavandula dentata and Lavandula stoechas extracts in two inflammatory experimental models: TNBS model of rat colitis and the carrageenan-induced paw edema in mice, in order to mimic the intestinal conditions and the extra-intestinal manifestations of human IBD, respectively. The extracts were characterized through the qualitative HPLC analysis. Then, they were assayed in vitro and in vivo. In vitro studies were performed in BMDMs and CMT-93 epithelial cells with different concentrations of the extracts (ranging from 0.1 to 100µg/ml). The extracts were tested in vivo in the TNBS model of rat colitis (10 and 25mg/kg) and in the carrageenan-induced paw edema in mice (10, 25 and 100mg/kg). L. dentata and L. stoechas extracts displayed immunomodulatory properties in vitro down-regulating different mediators of inflammation like cytokines and nitric oxide. They also showed anti-inflammatory effects in the TNBS model of colitis as evidenced by reduced myeloperoxidase activity and increased total glutathione content, indicating a decrease of neutrophil infiltration and an improvement of the oxidative state. Besides, both extracts modulated the expression of pro-inflammatory cytokines and chemokines, and ameliorated the altered epithelial barrier function. They also displayed anti-inflammatory effects in the carrageenan-induced paw edema in mice, since a significant reduction of the paw thickness was observed. This was associated with a down-regulation of the expression of different inducible enzymes like MMP-9, iNOS and COX-2 and pro-inflammatory cytokines, all involved in the maintenance of the inflammatory condition. L. dentata and L. stoechas extracts showed intestinal anti-inflammatory effect, confirming their potential use as herbal remedies in gastrointestinal disorders. In addition, their anti-inflammatory effect was also observed in other locations, thus suggesting a possible use for the treatment of the extra-intestinal symptoms of IBD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inhibitory Effect of Methyl 2-(4'-Methoxy-4'-oxobutanamide) Benzoate from Jerusalem Artichoke (Helianthus tuberosus) on the Inflammatory Paracrine Loop between Macrophages and Adipocytes.

PubMed

Jung, Yun Joo; Kim, Byung Oh; Kwak, Jong Hwan; Pyo, Suhkneung

2016-12-14

The interaction between macrophages and adipocytes is known to aggravate inflammation of the adipose tissue, leading to decreased insulin sensitivity. Hence, attenuation of the inflammatory paracrine loop between macrophages and adipocytes is deemed essential to ameliorate insulin resistance and diabetes mellitus type 2. Methyl 2-(4'-methoxy-4'-oxobutanamide) benzoate (compound 1), a newly isolated compound from Jerusalem srtichoke (JA), has not been biologically characterized yet. Here, we investigated whether JA-derived compound 1 attenuates the inflammatory cycle between RAW 264.7 macrophages and 3T3-L1 adipocytes. Compound 1 suppressed the inflammatory response of RAW 264.7 cells to lipopolysaccharide through decreased secretion of IL-1β, IL-6, and TNF-α. Moreover, the mRNA expression of TNF-α, IL-6, IL-1β, MCP-1, and Rantes and MAPK pathway activation in 3T3-L1 adipocytes, incubated in macrophage-conditioned media, were inhibited. These findings suggest an anti-inflammatory effect of a newly extracted compound against adipose tissue inflammation and insulin resistance.

Diet and Inflammation in Alzheimer's Disease and Related Chronic Diseases: A Review.

PubMed

Gardener, Samantha L; Rainey-Smith, Stephanie R; Martins, Ralph N

2016-01-01

Inflammation is one of the pathological features of the neurodegenerative disease, Alzheimer's disease (AD). A number of additional disorders are likewise associated with a state of chronic inflammation, including obesity, cardiovascular disease, and type-2 diabetes, which are themselves risk factors for AD. Dietary components have been shown to modify the inflammatory process at several steps of the inflammatory pathway. This review aims to evaluate the published literature on the effect of consumption of pro- or anti-inflammatory dietary constituents on the severity of both AD pathology and related chronic diseases, concentrating on the dietary constituents of flavonoids, spices, and fats. Diet-based anti-inflammatory components could lead to the development of potent novel anti-inflammatory compounds for a range of diseases. However, further work is required to fully characterize the therapeutic potential of such compounds, including gaining an understanding of dose-dependent relationships and limiting factors to effectiveness. Nutritional interventions utilizing anti-inflammatory foods may prove to be a valuable asset in not only delaying or preventing the development of age-related neurodegenerative diseases such as AD, but also treating pre-existing conditions including type-2 diabetes, cardiovascular disease, and obesity.

Antimicrobial and Attractant Roles for Chemerin in the Oral Cavity during Inflammatory Gum Disease

PubMed Central

Godlewska, Urszula; Brzoza, Piotr; Sroka, Aneta; Majewski, Pawel; Jentsch, Holger; Eckert, Martin; Eick, Sigrun; Potempa, Jan; Zabel, Brian A.; Cichy, Joanna

2017-01-01

Periodontal inflammation is one of the most common chronic inflammatory conditions in humans. Despite recent advances in identifying and characterizing oral microbiota dysbiosis in the pathogenesis of gum disease, just how host factors maintain a healthy homeostatic oral microbial community or prevent the development of a pathogenic oral microbiota remains poorly understood. An important determinant of microbiota fate is local antimicrobial proteins. Here, we report that chemoattractant protein chemerin, which we recently identified as a potent endogenous antimicrobial agent in body barriers such as the skin, is present in the oral cavity under homeostatic and inflammatory conditions. Chemerin and a chemerin-derived antimicrobial peptide are bactericidal against select bacteria strategically positioned in dental biofilm. Gingival crevicular samples from patients with gingivitis but not periodontitis contain abundant bioactive chemerin capable of inducing CMKLR1-dependent leukocyte migration. Gingipains secreted by the periodontopathogen P. gingivalis inactivate chemerin. Together, these data suggest that as an antimicrobial agent and leukocyte chemoattractant, chemerin likely contributes to antimicrobial immune defense in the oral cavity. PMID:28424689

Characterization of the anti-inflammatory Lactobacillus reuteri BM36301 and its probiotic benefits on aged mice.

PubMed

Lee, Joon; Yang, Woo; Hostetler, Andrew; Schultz, Nathan; Suckow, Mark A; Stewart, Kay L; Kim, Daniel D; Kim, Hyung Soo

2016-04-19

The gut microbiota is playing more important roles in host immune regulation than was initially expected. Since many benefits of microbes are highly strain-specific and their mechanistic details remain largely elusive, further identification of new probiotic bacteria with immunoregulatory potentials is of great interest. We have screened our collection of probiotic lactic acid bacteria (LAB) for their efficacy in modulating host immune response. Some LAB are characterized by suppression of TNF-α induction when LAB culture supernatants are added to THP-1 cells, demonstrating the LAB's anti-inflammatory potential. These suppressive materials were not inactivated by heat or trypsin. On the other hand, treatment of THP-1 directly with live bacterial cells identified a group of pro-inflammatory LAB, which stimulated significant production of TNF-α. Among those, we chose the Lactobacillus reuteri BM36301 as an anti-inflammatory strain and the L. reuteri BM36304 as a pro-inflammatory strain, and further studied their in vivo effects. We supplied C57BL/6 mice with these bacteria in drinking water while feeding them a standard diet for 20 weeks. Interestingly, these L. reuteri strains evoked different consequences depending on the gender of the mice. That is, males treated with anti-inflammatory BM36301 experienced less weight gain and higher testosterone level; females treated with BM36301 maintained lower serum TNF-α as well as healthy skin with active folliculogenesis and hair growth. Furthermore, while males treated with pro-inflammatory BM36304 developed higher serum levels of TNF-α and insulin, in contrast females did not experience such effects from this bacteria strain. The L. reuteri BM36301 was selected as an anti-inflammatory strain in vitro. It helped mice maintain healthy conditions as they aged. These findings propose the L. reuteri BM36301 as a potential probiotic strain to improve various aspects of aging issues.

Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood-Brain Barrier under Inflammatory Conditions In Vitro.

PubMed

De Laere, Maxime; Sousa, Carmelita; Meena, Megha; Buckinx, Roeland; Timmermans, Jean-Pierre; Berneman, Zwi; Cools, Nathalie

2017-01-01

Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood-brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated. Moreover, chemokine transport across BBB cocultures was upregulated, as evidenced by a significantly increased concentration of the inflammatory chemokine CCL3 at the luminal side following proinflammatory stimulation. CCL3 transport occurred independently of the chemokine receptors CCR1 and CCR5, albeit that migrated cells displayed increased expression of CCR1 and CCR5. However, overall leukocyte transmigration was reduced in inflammatory conditions, although higher numbers of leukocytes adhered to activated endothelial cells. Altogether, our findings demonstrate that prominent barrier activation following proinflammatory stimulation is insufficient to drive immune cell recruitment, suggesting that additional traffic cues are crucial to mediate the increased immune cell infiltration seen in vivo during neuroinflammation.

Folliculitis decalvans--response to rifampin.

PubMed

Brozena, S J; Cohen, L E; Fenske, N A

1988-12-01

Folliculitis decalvans is a rare follicular inflammatory disease of the scalp. It is characterized by initial perifollicular inflammatory changes followed by peripheral extension and eventual circumscribed patches of cicatricial alopecia. The disease is known for its resistance to treatment, resulting in an unfavorable prognosis. The cause of the disease is unknown, although a bacterial etiology is postulated. We report a classic case that was temporized with various antibiotics and only subsequently resolved after ten weeks of therapy with rifampin. The patient has remained free of disease for more than one year. We present a brief review of the cicatricial alopecias and discuss rifampin therapy for this condition.

PubMed

Kelle, Bayram; Yıldız, Fatih; Paydas, Semra; Bagır, Emine Kılıc; Ergin, Melek; Kozanoglu, Erkan

2014-12-23

Hypertrophic osteoarthropathy (HOA) is a condition characterized by arthralgia/arthritis, clubbing, and periosteal reaction. Primary form of HOA is observed at early ages of life and is hereditary in nature. Secondary HOA is more frequently seen in clinical setting and occurs as a result of various disorders including inflammatory and malignant diseases. Regression in HOA may be seen after the treatment of underlying condition. In this report, we presented a case of HOA coexisted with myelofibrosis and reviewed the current literature. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Role of immune cells in obesity induced low grade inflammation and insulin resistance.

PubMed

Asghar, Ambreen; Sheikh, Nadeem

2017-05-01

The frequency of obesity is enormously growing worldwide. Obesity results when energy intake exceeds, energy expenditure. Excess adiposity is a major risk factor in the progress of various metabolic disorders accounting insulin resistance, hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovarian disease and several types of cancers. Obesity is characterized by pro-inflammatory condition in which hypertrophied adipose tissue along with immune cells contribute to increase the level of pro-inflammatory cytokines. Immune cells are the key players in inducing low grade chronic inflammation in obesity and are main factor responsible for pathogenesis of insulin resistance resulting Type 2 diabetes. The current review is aimed to investigate the mechanism of pro-inflammatory responses and insulin resistance involving immune cells and their products in obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted pyrimidines.

PubMed

Yejella, Rajendra Prasad; Atla, Srinivasa Rao

2011-01-01

Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with various substituted aromatic and hetero aromatic aldehydes according to Claisen-Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in quantitative yields. All the newly synthesized pyrimidines were characterized by means of IR, ¹H- and ¹³C-NMR, Electron Ionization (EI)-mass and elemental analyses and screened for anti-inflammatory and analgesic activities by in vivo. 2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4-aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent anti-inflammatory and analgesic activity compared with ibuprofen, reference standard. And also it was found that compound 5b identified as lead structure among all in both the activities. Pyrimidines which showed good anti-inflammatory activity also displayed better analgesic activity.

Impact of Sub-Inhibitory Concentrations of Amoxicillin on Streptococcus suis Capsule Gene Expression and Inflammatory Potential.

PubMed

Haas, Bruno; Grenier, Daniel

2016-04-19

Streptococcus suis is an important swine pathogen and emerging zoonotic agent worldwide causing meningitis, endocarditis, arthritis and septicemia. Among the 29 serotypes identified to date, serotype 2 is mostly isolated from diseased pigs. Although several virulence mechanisms have been characterized in S. suis, the pathogenesis of S. suis infections remains only partially understood. This study focuses on the response of S. suis P1/7 to sub-inhibitory concentrations of amoxicillin. First, capsule expression was monitored by qRT-PCR when S. suis was cultivated in the presence of amoxicillin. Then, the pro-inflammatory potential of S. suis P1/7 culture supernatants or whole cells conditioned with amoxicillin was evaluated by monitoring the activation of the NF-κB pathway in monocytes and quantifying pro-inflammatory cytokines secreted by macrophages. It was found that amoxicillin decreased capsule expression in S. suis. Moreover, conditioning the bacterium with sub-inhibitory concentrations of amoxicillin caused an increased activation of the NF-κB pathway in monocytes following exposure to bacterial culture supernatants and to a lesser extent to whole bacterial cells. This was associated with an increased secretion of pro-inflammatory cytokines (CXCL8, IL-6, IL-1β) by macrophages. This study identified a new mechanism by which S. suis may increase its inflammatory potential in the presence of sub-inhibitory concentrations of amoxicillin, a cell wall-active antibiotic, thus challenging its use for preventive treatments or as growth factor.

PDGFRA-mutant syndrome.

PubMed

Ricci, Riccardo; Martini, Maurizio; Cenci, Tonia; Carbone, Arnaldo; Lanza, Paola; Biondi, Alberto; Rindi, Guido; Cassano, Alessandra; Larghi, Alberto; Persiani, Roberto; Larocca, Luigi M

2015-07-01

Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. 'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to 'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs, justifying the known predilection for stomach of sporadic PDGFRA-mutant GISTs. An awareness that inflammatory fibroid polyps, relatively common among gastrointestinal mesenchymal tumors, may be the prevailing tumor in PDGFRA-mutant syndrome could eventually reveal an unsuspected prevalence of this condition.

A peripheral immune response to remembering trauma contributes to the maintenance of fear memory in mice.

PubMed

Young, Matthew B; Howell, Leonard L; Hopkins, Lauren; Moshfegh, Cassandra; Yu, Zhe; Clubb, Lauren; Seidenberg, Jessica; Park, Jeanie; Swiercz, Adam P; Marvar, Paul J

2018-05-17

Alterations in peripheral immune markers are observed in individuals with post-traumatic stress disorder (PTSD). PTSD is characterized in part by impaired extinction of fear memory for a traumatic experience. We hypothesized that fear memory extinction is regulated by immune signaling stimulated when fear memory is retrieved. The relationship between fear memory and the peripheral immune response was tested using auditory Pavlovian fear conditioning in mice. Memory for the association was quantified by the amount of conditioned freezing exhibited in response to the conditioned stimulus (CS), extinction and time-dependent changes in circulating inflammatory cytokines. Brief extinction training with 12 CS rapidly and acutely increased circulating levels of the cytokine interleukin-6 (IL-6), downstream IL-6 signaling, other IL-6 related pro-inflammatory cytokines. Transgenic manipulations or neutralizing antibodies that inhibit IL-6 activity did not affect conditioned freezing during the acquisition of fear conditioning or extinction but significantly reduced conditioned freezing 24 h after extinction training with 12 CS. Conversely, conditioned freezing after extinction training was unchanged by IL-6 inhibition when 40 CS were used during the extinction training session. In addition to effectively diminishing conditioned freezing, extinction training with 40 CS also diminished the subsequent IL-6 response to the CS. These data demonstrate that IL-6 released following fear memory retrieval contributes to the maintenance of that fear memory and that this effect is extinction dependent. These findings extend the current understanding for the role of the immune system in PTSD and suggest that IL-6 and other IL-6 related pro-inflammatory cytokines may contribute to the persistence of fear memory in PTSD where fear memory extinction is impaired. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nanosized UCMSC-derived extracellular vesicles but not conditioned medium exclusively inhibit the inflammatory response of stimulated T cells: implications for nanomedicine.

PubMed

Monguió-Tortajada, Marta; Roura, Santiago; Gálvez-Montón, Carolina; Pujal, Josep Maria; Aran, Gemma; Sanjurjo, Lucía; Franquesa, Marcel la; Sarrias, Maria-Rosa; Bayes-Genis, Antoni; Borràs, Francesc E

2017-01-01

Undesired immune responses have drastically hampered outcomes after allogeneic organ transplantation and cell therapy, and also lead to inflammatory diseases and autoimmunity. Umbilical cord mesenchymal stem cells (UCMSCs) have powerful regenerative and immunomodulatory potential, and their secreted extracellular vesicles (EVs) are envisaged as a promising natural source of nanoparticles to increase outcomes in organ transplantation and control inflammatory diseases. However, poor EV preparations containing highly-abundant soluble proteins may mask genuine vesicular-associated functions and provide misleading data. Here, we used Size-Exclusion Chromatography (SEC) to successfully isolate EVs from UCMSCs-conditioned medium. These vesicles were defined as positive for CD9, CD63, CD73 and CD90, and their size and morphology characterized by NTA and cryo-EM. Their immunomodulatory potential was determined in polyclonal T cell proliferation assays, analysis of cytokine profiles and in the skewing of monocyte polarization. In sharp contrast to the non-EV containing fractions, to the complete conditioned medium and to ultracentrifuged pellet, SEC-purified EVs from UCMSCs inhibited T cell proliferation, resembling the effect of parental UCMSCs. Moreover, while SEC-EVs did not induce cytokine response, the non-EV fractions, conditioned medium and ultracentrifuged pellet promoted the secretion of pro-inflammatory cytokines by polyclonally stimulated T cells and supported Th17 polarization. In contrast, EVs did not induce monocyte polarization, but the non-EV fraction induced CD163 and CD206 expression and TNF-α production in monocytes. These findings increase the growing evidence confirming that EVs are an active component of MSC's paracrine immunosuppressive function and affirm their potential for therapeutics in nanomedicine. In addition, our results highlight the importance of well-purified and defined preparations of MSC-derived EVs to achieve the immunosuppressive effect.

Species-specific inflammatory responses as a primary component for the development of glomerular lesions in mice and monkeys following chronic administration of a second-generation antisense oligonucleotide.

PubMed

Frazier, Kendall S; Sobry, Cécile; Derr, Victoria; Adams, Mike J; Besten, Cathaline Den; De Kimpe, Sjef; Francis, Ian; Gales, Tracy L; Haworth, Richard; Maguire, Shaun R; Mirabile, Rosanna C; Mullins, David; Palate, Bernard; Doorten, Yolanda Ponstein-Simarro; Ridings, James E; Scicchitano, Marshall S; Silvano, Jérémy; Woodfine, Jennie

2014-07-01

Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration. Glomerulopathy occurred in both species with species-specific characteristics. Glomerular lesions in mice were characterized by progressive hyaline matrix accumulation, accompanied by the presence of renal amyloid and with subsequent papillary necrosis. Early changes involved glomerular endothelial hypertrophy and degeneration, but the chronic glomerular amyloid and hyaline alterations in mice appeared to be species specific. An immune-mediated mechanism for the glomerular lesions in mice was supported by early inflammatory changes including increased expression of inflammatory cytokines and other immunomodulatory genes within the renal cortex, increased stimulation of CD68 protein, and systemic elevation of monocyte chemotactic protein 1. In contrast, kidneys from monkeys given drisapersen chronically showed less severe glomerular changes characterized by increased mesangial and inflammatory cells, endothelial cell hypertrophy, and subepithelial and membranous electron-dense deposits, with ultrastructural and immunohistochemical characteristics of complement and complement-related fragments. Lesions in monkeys resembled typical features of C3 glomerulopathy, a condition described in man and experimental animals to be linked to dysregulation of the alternative complement pathway. Thus, inflammatory/immune mechanisms appear critical to glomerular injury with species-specific sensitivities for mouse and monkey. The lower observed proinflammatory activity in humans as compared to mice and monkeys may reflect a lower risk of glomerular injury in patients receiving AON therapy. © 2014 by The Author(s).

Chemical characterization and pharmacological assessment of polysaccharide free, standardized cashew gum extract (Anacardium occidentale L.).

PubMed

da Silva, Daiany Priscilla Bueno; Florentino, Iziara Ferreira; da Silva Moreira, Lorrane Kelle; Brito, Adriane Ferreira; Carvalho, Verônica Vale; Rodrigues, Marcella Ferreira; Vasconcelos, Géssica Adriana; Vaz, Boniek Gontijo; Pereira-Junior, Marcus Antônio; Fernandes, Kátia Flávia; Costa, Elson Alves

2018-03-01

The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances. In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE). The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE 2 levels, were performed the carrageenan or PGE 2 -induced hyperalgesia tests. The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented an antihyperalgic effect at all hours of the carrageenan-induced hyperalgesia test. However, this dose of CGE was not able to reduce the hyperalgesia induced by PGE 2 , suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE 2 levels. The anacardic acids are the predominant phytoconstituents identified in the CGE. The action mechanisms of CGE suggest the reduction in the PGE 2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition, independent of the presence of polysaccharides. Copyright © 2017 Elsevier B.V. All rights reserved.

Asymmetric synthesis of novel N-(1-phenyl-2,3-dihydroxypropyl)arachidonylamides and evaluation of their anti-inflammatory activity.

PubMed

Kattamuri, Padmanabha V; Salmonsen, Rebecca; McQuain, Catherine; Burstein, Sumner; Sun, Hao; Li, Guigen

2013-03-19

To design and synthesize novel N-(1-phenyl-2,3-dihydroxypropyl)arachidonylamides and evaluate their analgesic and anti-inflammatory potential. The murine macrophage cell line RAW 264.7 has been widely used as a model for inflammatory responses in vitro. Our model consists of cultured monolayers of RAW 264.7 cells in which media concentrations of 15-deoxy-Δ(13,14)-PGJ2 (PGJ) are measured by ELISA following LPS (10ng/ml) stimulation and treatment with 0.1, 0.3, 1.0, 3.0 and 10μM concentrations of the compounds. Our data indicate that several of our compounds have the capacity to increase production of PGJ and may also increase the occurrence of programmed cell death (apoptosis). Thus these agents are potential candidates for the therapy of conditions characterized by ongoing (chronic) inflammation and its associated pain. Copyright © 2012 Elsevier Inc. All rights reserved.

Inflammasome Activity in Non-Microbial Lung Inflammation

PubMed Central

Ather, Jennifer L.; Martin, Rebecca A.; Ckless, Karina; Poynter, Matthew E.

2015-01-01

The understanding of interleukin-1 (IL-1) family cytokines in inflammatory disease has rapidly developed, due in part to the discovery and characterization of inflammasomes, which are multi-subunit intracellular protein scaffolds principally enabling recognition of a myriad of cellular stimuli, leading to the activation of caspase-1 and the processing of IL-1β and IL-18. Studies continue to elucidate the role of inflammasomes in immune responses induced by both microbes and environmental factors. This review focuses on the current understanding of inflammasome activity in the lung, with particular focus on the non-microbial instigators of inflammasome activation, including inhaled antigens, oxidants, cigarette smoke, diesel exhaust particles, mineral fibers, and engineered nanomaterials, as well as exposure to trauma and pre-existing inflammatory conditions such as metabolic syndrome. Inflammasome activity in these sterile inflammatory states contribute to diseases including asthma, chronic obstructive disease, acute lung injury, ventilator-induced lung injury, pulmonary fibrosis, and lung cancer. PMID:25642415

Unsaponifiable fraction isolated from grape (Vitis vinifera L.) seed oil attenuates oxidative and inflammatory responses in human primary monocytes.

PubMed

Millan-Linares, Maria C; Bermudez, Beatriz; Martin, Maria E; Muñoz, Ernesto; Abia, Rocio; Millan, Francisco; Muriana, Francisco J G; Montserrat-de la Paz, Sergio

2018-04-25

Grape (Vitis vinifera L.) seed has well-known potential for production of oil as a byproduct of winemaking and is a rich source of bioactive compounds. Herein, we report that the unsaponifiable fraction (UF) isolated from grape seed oil (GSO) possesses anti-oxidative and anti-inflammatory properties towards human primary monocytes. The UF isolated from GSO was phytochemically characterized by GC-MS and HPLC. Freshly obtained human monocytes were used to analyse the effects of GSOUF (10-100 μg mL-1) on oxidative and inflammatory responses using FACS analysis, RT-qPCR, and ELISA procedures. GSOUF skewed the monocyte plasticity towards the anti-inflammatory non-classical CD14+CD16++ monocytes and reduced the inflammatory competence of LPS-treated human primary monocytes diminishing TNF-α, IL-1β, and IL-6 gene expression and secretion. In addition, GSOUF showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease in Nos2 gene expression. Our results suggest that the UF isolated from GSO has significant potential for the management of inflammatory and oxidative conditions and offer novel benefits derived from the consumption of GSO in the prevention of inflammation-related diseases.

Low level laser therapy reduces acute lung inflammation without impairing lung function.

PubMed

Cury, Vivian; de Lima, Thais Martins; Prado, Carla Maximo; Pinheiro, Nathalia; Ariga, Suely K K; Barbeiro, Denise F; Moretti, Ana I; Souza, Heraldo P

2016-12-01

Acute lung injury is a condition characterized by exacerbate inflammatory reaction in distal airways and lung dysfunction. Here we investigate the treatment of acute lung injury (ALI) by low level laser therapy (LLLT), an effective therapy used for the treatment of patients with inflammatory disorders or traumatic injuries, due to its ability to reduce inflammation and promote tissue regeneration. However, studies in internal viscera remains unclear. C57BL/6 mice were treated with intratracheal lipopolysaccharide (LPS) (5 mg/kg) or phosphate buffer saline (PBS). Six hours after instillation, two groups were irradiated with laser at 660 nm and radiant exposure of 10 J/cm 2 . Intratracheal LPS inoculation induced a marked increase in the number of inflammatory cells in perivascular and alveolar spaces. There was also an increase in the expression and secretion of cytokines (TNF-α, IL-1β, IL-6,) and chemokine (MCP-1). The LLLT application induced a significant decrease in both inflammatory cells influx and inflammatory mediators secretion. These effects did not affect lung mechanical properties, since no change was observed in tissue resistance or elastance. In conclusion LLLT is able to reduce inflammatory reaction in lungs exposed to LPS without affecting the pulmonary function and recovery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476

Detecting inflammation and fibrosis in bowel wall with photoacoustic imaging in a Crohn's disease animal model

NASA Astrophysics Data System (ADS)

Xu, Guan; Johnson, Laura A.; Hu, Jack; Dillman, Jonathan R.; Higgins, Peter D. R.; Wang, Xueding

2015-03-01

Crohn's disease (CD) is an autoimmune disease affecting 700,000 people in the United States. This condition may cause obstructing intestinal narrowings (strictures) due to inflammation, fibrosis (deposition of collagen), or a combination of both. Utilizing the unique strong optical absorption of hemoglobin at 532 nm and collagen at 1370 nm, this study investigated the feasibility of non-invasively characterizing intestinal strictures using photoacoustic imaging (PAI). Three normal controls, ten pure inflammation and 9 inflammation plus fibrosis rat bowel wall samples were imaged. Statistical analysis of the PA measurements has shown the capability of discriminating the purely inflammatory from mixed inflammatory and fibrotic strictures.

Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

PubMed Central

Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

2017-01-01

Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer. PMID:28264501

Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

PubMed

Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

2017-02-28

Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

Clinical effects of diet supplementation with DHA in pediatric patients suffering from cystic fibrosis.

PubMed

Leggieri, E; De Biase, R V; Savi, D; Zullo, S; Halili, I; Quattrucci, S

2013-08-01

Cystic fibrosis (CF) patients present an altered fatty acid (FA) metabolism characterized by imbalance in the arachidonic/docosohexasenoic acid (AA/DHA) ratio in favour of the former which can contribute to the increase in pulmonary inflammation. The present study aims to assess respiratory, nutritional, clinical and laboratory parameters, and inflammatory markers after six months of DHA supplementation in paediatric patients suffering from CF. A dose of 1 g/10 kg/die was administered to ten CF patients of paediatric age for the first month and 250 mg/10 kg/die for the remaining 5 months. We carried out follow-ups at T0 (baseline), T6 (after six months of the diet) and T12 (six months after supplementation was interrupted) during which respiratory, nutritional, clinical and laboratory parameters were assessed. After six months of DHA supplementation inflammatory marker levels had diminished: interleukin 8 (IL-8) and Tumour Necrosis Factor Alfa (TNF-α) in serum, and calprotectin in stools. In addition, auxometric parameters were improved as was the clinical condition of patients, who tolerated DHA well. Dietetic integration with DHA seems to improve clinical condition and the inflammatory pulmonary and intestinal state of pediatric patients suffering from CF.

Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.

PubMed

McKinnon, R; Binder, M; Zupkó, I; Afonyushkin, T; Lajter, I; Vasas, A; de Martin, R; Unger, C; Dolznig, H; Diaz, R; Frisch, R; Passreiter, C M; Krupitza, G; Hohmann, J; Kopp, B; Bochkov, V N

2014-10-15

Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data. The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats. The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats. Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

Dose-dependent antiinflammatory effect of ursodeoxycholic acid in experimental colitis.

PubMed

Martínez-Moya, Patricia; Romero-Calvo, Isabel; Requena, Pilar; Hernández-Chirlaque, Cristina; Aranda, Carlos J; González, Raquel; Zarzuelo, Antonio; Suárez, María Dolores; Martínez-Augustin, Olga; Marín, José Juan G; de Medina, Fermín Sánchez

2013-02-01

The denomination of inflammatory bowel disease comprises a group of chronic inflammatory diseases of the digestive tract, ulcerative colitis and Crohn's disease being the most important conditions. Bile acids may play a role both in etiology and pharmacology of this disease. Thus, although deoxycholic acid is regarded as a proinflammatory agent ursodeoxycholic acid, which is currently being used to treat certain types of cholestasis and primary biliary cirrhosis, because of their choleretic, cytoprotective and immunomodulatory effects, it has been reported to exert an anti-inflammatory activity. We aim to confirm and characterize the intestinal antiinflammatory activity of ursodeoxycholic acid. The experimental model trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats has been used. Animal status was characterized by a number of macroscopic and biochemical parameters. Oral administration of ursodeoxycholic acid was able to ameliorate experimental colonic inflammation. This occurred only at a relatively high dose (50 mg/kg day), whereas ursodeoxycholic acid was without significant effect at doses of 10 and 25 mg/kg day. The therapeutic effect was evidenced, among others, by a higher body weight recovery, a diminished affected to total mucosal area and lower alkaline phosphatase activity in treated vs. control (TNBS treated) animals. These results indicate that, at the appropriate dose, ursodeoxycholic acid is a potentially useful drug to reduce intestinal inflammation and could be envisaged to be incorporated in the treatment of inflammatory bowel diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

The salivary proteome profile in patients affected by SAPHO syndrome characterized by a top-down RP-HPLC-ESI-MS platform.

PubMed

Sanna, Monica; Firinu, Davide; Manconi, Paolo Emilio; Pisanu, Maria; Murgia, Giuseppe; Piras, Valentina; Castagnola, Massimo; Messana, Irene; del Giacco, Stefano Renato; Cabras, Tiziana

2015-06-01

SAPHO syndrome is a rare and often unrecognized disease with prominent inflammatory cutaneous and articular symptoms characterized by musculoskeletal manifestations (synovitis, hyperostosis, osteomyelitis) associated with dermatological conditions (severe acne and pustulosis). The acidic soluble fraction of whole saliva from 10 adult women affected by SAPHO syndrome and from a group of 28 healthy women was analysed by RP-HPLC-ESI-MS with the aim of discovering salivary biomarkers of the disorder. The levels of the oral proteins and peptides were correlated with clinical data. The following proteins showed a significant decreased concentration in saliva of SAPHO subjects with respect to controls: cystatin S1 and SN, histatins, the major acidic PRPs, P-C and P-B peptides. The cystatin SN abundance lowered according to the disease duration and histatins showed positive correlations with the C reactive protein. Statistical analysis performed excluding one patient with a different pattern of salivary proteins/peptides highlighted a positive relationship between cystatin S1, histatins 3, histatin 5, and the neutrophil count. Moreover, histatin 3 correlated positively with the total white cell count and negatively with the erythrocyte sedimentation rate. Levels and frequency of S100A12 protein showed a trend to increase in SAPHO patients. The high expression of this pro-inflammatory protein is probably related to the inflammatory response and to the altered neutrophil responses to functional stimuli that characterize SAPHO syndrome suggesting a possible application as a salivary biomarker.

Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models.

PubMed

Hajhashemi, Valiollah; Klooshani, Vahid

2013-01-01

This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects. The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%. The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract.

Links demystified: Periodontitis and cancer

PubMed Central

Pendyala, Gowri; Joshi, Saurabh; Chaudhari, Shantanu; Gandhage, Dhananjay

2013-01-01

Cancer is marked by the uncontrolled growth of cells, tissue invasion and metastasis to various organs via the circulatory and lymphatic systems. Recent data have expanded the concept that inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. The tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Periodontal disease, a chronic inflammatory condition is characterized by an oral bacterial infection leading to inflammation within the supporting tissues of the teeth, which often leads to the destruction of the periodontal tissues and alveolar bone that support the teeth. This oral inflammation often has systemic effects leading to an increased concentration of circulating inflammatory markers with the severity of disease being correlated directly with levels of serum inflammatory markers. Periodontal infection has been linked to organ and systemic diseases. There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers, and periodontal disease. This articles reviews and summarizes the possible biological mechanisms involved between periodontal infection and cancer. PMID:24379856

Links demystified: Periodontitis and cancer.

PubMed

Pendyala, Gowri; Joshi, Saurabh; Chaudhari, Shantanu; Gandhage, Dhananjay

2013-11-01

Cancer is marked by the uncontrolled growth of cells, tissue invasion and metastasis to various organs via the circulatory and lymphatic systems. Recent data have expanded the concept that inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. The tumor microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival, and migration. Periodontal disease, a chronic inflammatory condition is characterized by an oral bacterial infection leading to inflammation within the supporting tissues of the teeth, which often leads to the destruction of the periodontal tissues and alveolar bone that support the teeth. This oral inflammation often has systemic effects leading to an increased concentration of circulating inflammatory markers with the severity of disease being correlated directly with levels of serum inflammatory markers. Periodontal infection has been linked to organ and systemic diseases. There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers, and periodontal disease. This articles reviews and summarizes the possible biological mechanisms involved between periodontal infection and cancer.

Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity.

PubMed

Pereira, Regina M S; Andrades, Norma E D; Paulino, Niraldo; Sawaya, Alexandra C H F; Eberlin, Marcos N; Marcucci, Maria C; Favero, Giovani Marino; Novak, Estela Maria; Bydlowski, Sérgio Paulo

2007-07-09

The antioxidant activity of flavonoids is believed to increase when they are coordinated with transition metal ions. However, the literature on this subject is contradictory and the outcome seems to largely depend on the experimental conditions. In order to understand the contribution of the metal coordination and the type of interaction between a flavonoid and the metal ion, in this study a new metal complex of Cu (II) with naringin was synthesized and characterized by FT-IR, UV-VIS, mass spectrometry (ESI-MS/MS), elemental analysis and 1H-NMR. The results of these analyses indicate that the complex has a Cu (II) ion coordinated via positions 4 and 5 of the flavonoid. The antioxidant, anti-inflammatory and antimicrobial activities of this complex were studied and compared with the activity of free naringin. The Naringin-Cu (II) complex 1 showed higher antioxidant, anti-inflammatory and tumor cell cytotoxicity activities than free naringin without reducing cell viability.

Mass-spectrometric analysis of hydroperoxy- and hydroxy-derivatives of cardiolipin and phosphatidylserine in cells and tissues induced by pro-apoptotic and pro-inflammatory stimuli

PubMed Central

Tyurin, Vladimir A.; Tyurina, Yulia Y.; Jung, Mi-Yeon; Tungekar, Muhammad A.; Wasserloos, Karla J.; Bayir, Hülya; Greenberger, Joel S.; Kochanek, Patrick M.; Shvedova, Anna A.; Pitt, Bruce; Kagan, Valerian E.

2009-01-01

Oxidation of two anionic phospholipids - cardiolipin (CL) in mitochondria and phosphatidylserine (PS) in extramitochondrial compartments - are important signaling events, particularly during the execution of programmed cell death and clearance of apoptotic cells. Quantitative analysis of CL and PS oxidation products is central to understanding their molecular mechanisms of action. We combined the identification of diverse phospholipid molecular species by ESI-MS with quantitative assessments of lipid hydroperoxides using a fluorescence HPLC-based protocol. We characterized CL and PS oxidation products formed in a model system (cyt c/H2O2), in apoptotic cells (neurons, pulmonary artery endothelial cells) and mouse lung under inflammatory/oxidative stress conditions (hyperoxia, inhalation of single walled carbon nanotubes). Our results demonstrate the usefulness of this approach for quantitative assessments, identification of individual molecular species and structural characterization of anionic phospholipids that are involved in oxidative modification in cells and tissues. PMID:19328050

Tie2 signaling cooperates with TNF to promote the pro-inflammatory activation of human macrophages independently of macrophage functional phenotype.

PubMed

García, Samuel; Krausz, Sarah; Ambarus, Carmen A; Fernández, Beatriz Malvar; Hartkamp, Linda M; van Es, Inge E; Hamann, Jörg; Baeten, Dominique L; Tak, Paul P; Reedquist, Kris A

2014-01-01

Angiopoietin (Ang) -1 and -2 and their receptor Tie2 play critical roles in regulating angiogenic processes during development, homeostasis, tumorigenesis, inflammation and tissue repair. Tie2 signaling is best characterized in endothelial cells, but a subset of human and murine circulating monocytes/macrophages essential to solid tumor formation express Tie2 and display immunosuppressive properties consistent with M2 macrophage polarization. However, we have recently shown that Tie2 is strongly activated in pro-inflammatory macrophages present in rheumatoid arthritis patient synovial tissue. Here we examined the relationship between Tie2 expression and function during human macrophage polarization. Tie2 expression was observed under all polarization conditions, but was highest in IFN-γ and IL-10 -differentiated macrophages. While TNF enhanced expression of a common restricted set of genes involved in angiogenesis and inflammation in GM-CSF, IFN-γ and IL-10 -differentiated macrophages, expression of multiple chemokines and cytokines, including CXCL3, CXCL5, CXCL8, IL6, and IL12B was further augmented in the presence of Ang-1 and Ang-2, via Tie2 activation of JAK/STAT signaling. Conditioned medium from macrophages stimulated with Ang-1 or Ang-2 in combination with TNF, sustained monocyte recruitment. Our findings suggest a general role for Tie2 in cooperatively promoting the inflammatory activation of macrophages, independently of polarization conditions.

Thiol oxidation and di-tyrosine formation in human plasma proteins induced by inflammatory concentrations of hypochlorous acid.

PubMed

Colombo, Graziano; Clerici, Marco; Altomare, Alessandra; Rusconi, Francesco; Giustarini, Daniela; Portinaro, Nicola; Garavaglia, Maria Lisa; Rossi, Ranieri; Dalle-Donne, Isabella; Milzani, Aldo

2017-01-30

In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics. Mass spectrometry (MS) analysis was performed to elucidate the protein composition of HMW aggregates. α1-antitrypsin, transthyretin, and haptoglobin showed thiol oxidation at HOCl concentrations higher than those causing complete oxidation of albumin. At the highest HOCl concentrations, formation of carbonylated and di-tyrosine cross-linked HMW protein aggregates also occurred. MS analysis identified fibrinogen, complement C3 and apolipoprotein A-I as components of HMW protein aggregates. These results could be relevant for human diseases characterized by inflammatory conditions in which myeloperoxidase and HOCl are involved. In this study we evaluated the oxidative damage occurring on plasma proteins when reconstituted human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). Pathophysiological concentrations of HOCl are able to induce different modifications on plasma proteins such as carbonylation, sulfhydryl oxidation and formation of high molecular weight (HMW) protein aggregates characterized by di-tyrosine fluorescence. There are two relevant aspects emerging from this paper. The first one consists on identifying low abundant proteins undergoing sulfhydryl oxidation by biotin-maleimide derivatization followed by MALDI-TOF mass spectrometry. This approach suggests three low-abundant proteins undergoing HOCl-induced oxidation: transthyretin, α1-antitrypsin, and haptoglobin. In addition, we analysed HMW protein aggregates forming after HOCl exposure. These aggregates are characterized by carbonylation, intra- and/or intermolecular di-tyrosine bridges. After their isolation from SDS-PAGE gel electrophoresis, using electrospray tandem mass spectrometry coupled to reversed-phase nanoscale capillary liquid chromatography, we identified some protein constituents of these HMW aggregates such as α, β, γ fibrinogen chains, apolipoprotein A-I and complement C3. In particular, our work highlights how fibrinogen is an important constituent of HOCl-induced HMW protein aggregates validating the mass spectrometry result with additional experiments. Further investigations are required in order to evaluate the possibility to use carbonylated and di-Tyr cross-linked HMW protein aggregates as (early) biomarkers for disease progression in inflammatory conditions in which myeloperoxidase and HOCl are involved. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel ex vivo culture method for human monocytes uses shear flow to prevent total loss of transendothelial diapedesis function.

PubMed

Tsubota, Yoshiaki; Frey, Jeremy M; Raines, Elaine W

2014-01-01

Monocyte recruitment to inflammatory sites and their transendothelial migration into tissues are critical to homeostasis and pathogenesis of chronic inflammatory diseases. However, even short-term suspension culture of primary human monocytes leads to phenotypic changes. In this study, we characterize the functional effects of ex vivo monocyte culture on the steps involved in monocyte transendothelial migration. Our data demonstrate that monocyte diapedesis is impaired by as little as 4 h culture, and the locomotion step is subsequently compromised. After 16 h in culture, monocyte diapedesis is irreversibly reduced by ∼90%. However, maintenance of monocytes under conditions mimicking physiological flow (5-7.5 dyn/cm²) is sufficient to reduce diapedesis impairment significantly. Thus, through the application of shear during ex vivo culture of monocytes, our study establishes a novel protocol, allowing functional analyses of monocytes not currently possible under static culture conditions. These data further suggest that monocyte-based therapeutic applications may be measurably improved by alteration of ex vivo conditions before their use in patients.

Pseudomembranous Colitis

PubMed Central

Farooq, Priya D.; Urrunaga, Nathalie H.; Tang, Derek M.; von Rosenvinge, Erik C.

2015-01-01

Pseudomembranous colitis is an inflammatory condition of the colon characterized by elevated yellow-white plaques that coalesce to form pseudomembranes on the mucosa. Patients with the condition commonly present with abdominal pain, diarrhea, fever, and leukocytosis. Because pseudomembranous colitis is often associated with C. difficile infection, stool testing and empiric antibiotic treatment should be initiated when suspected. When results of C. difficile testing are negative and symptoms persist despite escalating empiric treatment, early gastroenterology consultation and lower endoscopy would be the next step in the appropriate clinical setting. If pseudomembranous colitis is confirmed endoscopically, colonic biopsies should be obtained, as histology can offer helpful clues to the underlying diagnosis. The less common non-C. difficile causes of pseudomembranous colitis should be entertained, as a number of etiologies can result in this condition. Examples include Behcet’s disease, collagenous colitis, inflammatory bowel disease, ischemic colitis, other infections organisms (e.g. bacteria, parasites, viruses), and a handful of drugs and toxins. Pinpointing the correct underlying etiology would better direct patient care and disease management. Surgical specialists would be most helpful in colonic perforation, gangrenous colon, or severe disease. PMID:25769243

Discovery of potent and selective small-molecule PAR-2 agonists.

PubMed

Seitzberg, Jimmi Gerner; Knapp, Anne Eeg; Lund, Birgitte Winther; Mandrup Bertozzi, Sine; Currier, Erika A; Ma, Jian-Nong; Sherbukhin, Vladimir; Burstein, Ethan S; Olsson, Roger

2008-09-25

Proteinase activated receptor-2 plays a crucial role in a wide variety of conditions with a strong inflammatory component. We present the discovery and characterization of two structurally different, potent, selective, and metabolically stable small-molecule PAR-2 agonists. These ligands may be useful as pharmacological tools for elucidating the complex physiological role of the PAR-2 receptors as well as for the development of PAR-2 antagonists.

Structural and physicochemical characterization of pyridine derivative salts of anti-inflammatory drugs

NASA Astrophysics Data System (ADS)

Nechipadappu, Sunil Kumar; Trivedi, Darshak R.

2017-08-01

Salts of common anti-inflammatory drugs mefenamic acid (MFA), tolfenamic acid (TFA) and naproxen (NPX) with various pyridine derivatives (4-amino pyridine (4AP), 4-dimethylaminopyridine (DMAP) and 2-amino pyridine (2AP)) were synthesized by crystal engineering approach based on the pKa values of API's and the salt former. All the salts were characterized systematically by various spectroscopic methods including FT-IR and 1H NMR and the crystal structure was determined by single-crystal X-ray diffraction techniques (SCXRD). DMAP salt of NPX and 2AP salts of MFA and TFA were not obtained in the salt screening experiments. All the molecular salts exhibited 1:1 molecular stoichiometry in the asymmetric unit and except NPX-2AP salt, all the molecular salts included a water molecule in the crystal lattice. Physicochemical and structural properties between drug-drug molecular salts of MFA-4AP, TFA-4AP and NPX-4AP have been evaluated and it was found that these molecular salts were found to be stable for a time period of six months at ambient condition and further hydration of molecular salts were not observed even at accelerated humid conditions (∼75% RH). It was found that 4AP salts of MFA and TFA and DMAP salts of MFA and TFA are isostructural.

The link between chronic periodontitis and COPD: a common role for the neutrophil?

PubMed Central

2013-01-01

Background The possible relationship between chronic inflammatory diseases and their co-morbidities has become an increasing focus of research. Both chronic periodontitis and chronic obstructive pulmonary disease are neutrophilic, inflammatory conditions characterized by the loss of local connective tissue. Evidence suggests an association and perhaps a causal link between the two diseases. However, the nature of any relationship between them is unclear, but if pathophysiologically established may have wide-reaching implications for targeted treatments to improve outcomes and prognosis. Discussion There have been a number of epidemiological studies undertaken demonstrating an independent association between chronic periodontitis and chronic obstructive pulmonary disease. However, many of them have significant limitations, and drawing firm conclusions regarding causality may be premature. Although the pathology of both these diseases is complex and involves many cell types, such as CD8 positive cells and macrophages, both conditions are predominantly characterized by neutrophilic inflammation. Increasingly, there is evidence that the two conditions are underpinned by similar pathophysiological processes, especially centered on the functions of the neutrophil. These include a disturbance in protease/anti-protease and redox state balance. The association demonstrated by epidemiological studies, as well as emerging similarities in pathogenesis at the level of the neutrophil, suggest a basis for testing the effects of treatment for one condition upon the severity of the other. Summary Although the evidence of an independent association between chronic periodontitis and chronic obstructive pulmonary disease grows stronger, there remains a lack of definitive studies designed to establish causality and treatment effects. There is a need for future research to be focused on answering these questions. PMID:24229090

Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors?

PubMed Central

Hobbins, Stephanie; Chapple, Iain LC; Sapey, Elizabeth; Stockley, Robert A

2017-01-01

COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes. Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies. As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes. The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions. However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies. Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis. This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms. It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors. Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases. However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships. PMID:28496317

Is periodontitis a comorbidity of COPD or can associations be explained by shared risk factors/behaviors?

PubMed

Hobbins, Stephanie; Chapple, Iain Lc; Sapey, Elizabeth; Stockley, Robert A

2017-01-01

COPD is recognized as having a series of comorbidities potentially related to common inflammatory processes. Periodontitis is one of the most common human inflammatory diseases and has previously been associated with COPD in numerous observational studies. As periodontitis and COPD are both chronic, progressive conditions characterized by neutrophilic inflammation with subsequent proteolytic destruction of connective tissue, it has been proposed that they share common pathophysiological processes. The mechanisms proposed to link COPD and periodontitis include mechanical aspiration of oral contents into the respiratory tree, overspill of locally produced inflammatory mediators into the systemic circulation or oral or lung-derived bacteremia activating an acute-phase response and also reactive oxygen species (ROS) and cytokine release by systemic neutrophils at distant sites. Studies of systemic neutrophils in COPD and chronic periodontitis describe altered cellular functions that would predispose to inflammation and tissue destruction both in the lung and in the mouth, again potentially connecting these conditions. However, COPD and periodontitis also share risk factors such as age, chronic tobacco smoke exposure, and social deprivation that are not always considered in observational and interventional studies. Furthermore, studies reporting associations have often utilized differing definitions of both COPD and periodontitis. This article reviews the current available evidence supporting the hypothesis that COPD and inflammatory periodontal disease (periodontitis) could be pathologically associated, including a review of shared inflammatory mechanisms. It highlights the potential limitations of previous studies, in particular, the lack of uniformly applied case definitions for both COPD and periodontitis and poor recognition of shared risk factors. Understanding associations between these conditions may inform why patients with COPD suffer such a burden of comorbid illness and new therapeutic strategies for both the diseases. However, further research is needed to clarify factors that may be directly causal as opposed to confounding relationships.

Orbital inflammatory disease: Pictorial review and differential diagnosis

PubMed Central

Pakdaman, Michael N; Sepahdari, Ali R; Elkhamary, Sahar M

2014-01-01

Orbital inflammatory disease (OID) represents a collection of inflammatory conditions affecting the orbit. OID is a diagnosis of exclusion, with the differential diagnosis including infection, systemic inflammatory conditions, and neoplasms, among other conditions. Inflammatory conditions in OID include dacryoadenitis, myositis, cellulitis, optic perineuritis, periscleritis, orbital apicitis, and a focal mass. Sclerosing orbital inflammation is a rare condition with a chronic, indolent course involving dense fibrosis and lymphocytic infiltrate. Previously thought to be along the spectrum of OID, it is now considered a distinct pathologic entity. Imaging plays an important role in elucidating any underlying etiology behind orbital inflammation and is critical for ruling out other conditions prior to a definitive diagnosis of OID. In this review, we will explore the common sites of involvement by OID and discuss differential diagnosis by site and key imaging findings for each condition. PMID:24778772

Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential.

PubMed

Spitz, Charlotte; Winkels, Holger; Bürger, Christina; Weber, Christian; Lutgens, Esther; Hansson, Göran K; Gerdes, Norbert

2016-03-01

Atherosclerosis is a chronic inflammatory disease that is mediated by innate and adaptive immune responses. The disease is characterized by sub-endothelial accumulation and modification of lipids in the artery wall triggering an inflammatory reaction which promotes lesion progression and eventual plaque rupture, thrombus formation, and the respective clinical sequelae such as myocardial infarction or stroke. During the past decade, T-cell-mediated immune responses, especially control of pro-inflammatory signals by regulatory T cells (Tregs), have increasingly attracted the interest of experimental and clinical researchers. By suppression of T cell proliferation and secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-β, Tregs exert their atheroprotective properties. Atherosclerosis-prone, hyperlipidemic mice harbor systemically less Tregs compared to wild-type mice, suggesting an imbalance of immune cells which affects local and systemic inflammatory and potentially metabolic processes leading to atherogenesis. Restoring or increasing Treg frequency and enhancing their suppressive capacity by various modulations may pose a promising approach for treating inflammatory conditions such as cardiovascular diseases. In this review, we briefly summarize the immunological basics of atherosclerosis and introduce the role and contribution of different subsets of T cells. We then discuss experimental data and current knowledge pertaining to Tregs in atherosclerosis and perspectives on manipulating the adaptive immune system to alleviate atherosclerosis and cardiovascular disease.

Role of Peroxisome Proliferator-Activated Receptors in Inflammation Control

PubMed Central

Badr, Mostafa

2004-01-01

Peroxisome proliferator-activated receptors (PPARs) were discovered over a decade ago, and were classified as orphan members of the nuclear receptor superfamily. To date, three PPAR subtypes have been discovered and characterized (PPARα, β/δ, γ). Different PPAR subtypes have been shown to play crucial roles in important diseases and conditions such as obesity, diabetes, atherosclerosis, cancer, and fertility. Among the most studied roles of PPARs is their involvement in inflammatory processes. Numerous studies have revealed that agonists of PPARα and PPARγ exert anti-inflammatory effects both in vitro and in vivo. Using the carrageenan-induced paw edema model of inflammation, a recent study in our laboratories showed that these agonists hinder the initiation phase, but not the late phase of the inflammatory process. Furthermore, in the same experimental model, we recently also observed that activation of PPARδ exerted an anti-inflammatory effect. Despite the fact that exclusive dependence of these effects on PPARs has been questioned, the bulk of evidence suggests that all three PPAR subtypes, PPARα, δ, γ, play a significant role in controlling inflammatory responses. Whether these subtypes act via a common mechanism or are independent of each other remains to be elucidated. However, due to the intensity of research efforts in this area, it is anticipated that these efforts will result in the development of PPAR ligands as therapeutic agents for the treatment of inflammatory diseases. PMID:15292582

In vitro adhesion and anti-inflammatory properties of native Lactobacillus fermentum and Lactobacillus delbrueckii spp.

PubMed

Archer, A C; Kurrey, N K; Halami, P M

2018-03-14

This study aimed at characterizing the adhesion and immune-stimulatory properties of native probiotic Lactobacillus fermentum (MCC 2759 and MCC 2760) and Lactobacillus delbrueckii MCC 2775. Adhesion of the strains was assessed in Caco-2 and HT-29 cell lines. Expression of adhesion and immune markers were evaluated in Caco-2 cells by real-time qPCR. The cultures displayed >80% of adhesion to both cell lines and also induced the expression of mucin-binding protein (mub) gene in the presence of mucin, bile and pancreatin. Adhesion was mediated by carbohydrate and proteinaceous factors. The cultures stimulated the expression of inflammatory cytokines in Caco-2 cells. However, pro-inflammatory genes were down-regulated upon challenge with lipopolysaccharide and IL-10 was up-regulated by the cultures. Cell wall extract of L. fermentum MCC 2760 induced the expression of IL-6 by 5·47-fold, whereas crude culture filtrate enhanced the expression of IL-10 by 14·87-fold compared to LPS control. The bacterial cultures exhibited strong adhesion and anti-inflammatory properties. This is the first report to reveal the role of adhesion markers of L. fermentum and L. delbrueckii by qPCR. The strain-specific anti-inflammatory property of native cultures may be useful to alleviate inflammatory conditions and develop a target-based probiotic. © 2018 The Society for Applied Microbiology.

Impact of antibiotics on the microcirculation in local and systemic inflammation.

PubMed

Al-Banna, N A; Pavlovic, D; Gründling, M; Zhou, J; Kelly, M; Whynot, S; Hung, O; Johnston, B; Issekutz, T B; Kern, H; Cerny, V; Lehmann, Ch

2013-01-01

The main function of antibiotics is related to their capacity to eliminate a microorganism. In addition to the antimicrobial function of antibiotics, they are known to have anti-inflammatory and vasomodulatory effects on the microcirculation. The ability of non-antimicrobial derivatives of antibiotics to control inflammation illustrates the distinct anti-microbial and anti-inflammatory roles of antibiotics. In this review, we discuss the impact of antibiotics on leukocyte recruitment and the state of the microcirculation. Literature reporting the effect of antibiotics in non-infectious inflammatory conditions is reviewed as well as the studies demonstrating the anti-inflammatory effects of antibiotics in animal models of infection. In addition, the effect of the antibiotics on the immune system is summarized in this review, in order to postulate some mechanisms of action for the proand anti-inflammatory contribution of antibiotics. Literature reported the effect of antibiotics on the production of cytokines, chemotaxis and recruitment of leukocytes, production of reactive oxygen species, process of phagocytosis and autophagy, and apoptosis of leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory effect on the microcirculation. Thus, we suggest a model for spectrum of anti-inflammatory and vasomodulatory effects of antibiotics in the microcirculation of animals in local and systemic inflammation. Although the literature suggests the ability of antibiotics to modulate leukocyte recruitment and microperfusion, the process and the mechanism of action are not fully characterized. Studying this process will expand the knowledge base that is required for the selection of antibiotic treatment based on its anti-inflammatory functions, which might be particularly important for critically ill patients.

Colonization with Heligmosomoides polygyrus suppresses mucosal IL-17 production

USDA-ARS?s Scientific Manuscript database

Helminth exposure appears to protect hosts from inappropriate inflammatory responses, such as those causing inflammatory bowel disease. A recently identified, strongly pro-inflammatory limb of the immune response is characterized by T cell IL-17 production. Many autoimmune-type inflammatory diseases...

The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

PubMed Central

Cardoso, Ana; Gil Castro, Antonio; Martins, Ana Catarina; Carriche, Guilhermina M.; Murigneux, Valentine; Castro, Isabel; Cumano, Ana; Vieira, Paulo; Saraiva, Margarida

2018-01-01

Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection. PMID:29545807

Isolated and combined effects of photobiomodulation therapy, topical nonsteroidal anti-inflammatory drugs, and physical activity in the treatment of osteoarthritis induced by papain

NASA Astrophysics Data System (ADS)

Tomazoni, Shaiane Silva; Leal-Junior, Ernesto Cesar Pinto; Frigo, Lúcio; Pallotta, Rodney Capp; Teixeira, Simone; de Almeida, Patricia; Bjordal, Jan Magnus; Lopes-Martins, Rodrigo Álvaro Brandão

2016-10-01

Osteoarthritis (OA) is a chronic inflammatory disease and is characterized as a degenerative process. This study aimed to evaluate and compare the effects of a topical nonsteroidal anti-inflammatory drug (NSAID), physical activity, and photobiomodulation therapy (PBMT) applied alone and/or in combination between them in an experimental model of knee OA. OA was induced by injection of papain in the knees of rats. After 21 days, the animals started to be treated with the above treatment. Histological analysis shows that the experimental model of OA induction causes morphological changes consistent with the disease, and among treatments, the PBMT is the most effective for reducing these changes. Moreover, the results demonstrate that PBMT and NSAID reduce the total number of cells in the inflammatory infiltrate (p<0.05) and PBMT was the most effective for reducing the activity of myeloperoxidase (p<0.05). Finally, we observed that both NSAID and PBMT were effective for reducing the gene expression of MMP-3 (p<0.05), but in relation to the gene expression of MMP-13, PBMT was the most effective treatment (p<0.05). The results of this study indicate that PBMT is the most effective therapy in stopping disease progression, and improving inflammatory conditions observed in OA.

Can inflammatory bowel disease be permanently treated with short-term interventions on the microbiome?

PubMed

Berg, Dana; Clemente, Jose C; Colombel, Jean-Frederic

2015-06-01

Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is a chronic, relapsing and remitting set of conditions characterized by an excessive inflammatory response leading to the destruction of the gastrointestinal tract. While the exact etiology of inflammatory bowel disease remains unclear, increasing evidence suggests that the human gastrointestinal microbiome plays a critical role in disease pathogenesis. Manipulation of the gut microbiome has therefore emerged as an attractive alternative for both prophylactic and therapeutic intervention against inflammation. Despite its growing popularity among patients, review of the current literature suggests that the adult microbiome is a highly stable structure resilient to short-term interventions. In fact, most evidence to date demonstrates that therapeutic agents targeting the microflora trigger rapid changes in the microbiome, which then reverts to its pre-treatment state once the therapy is completed. Based on these findings, our ability to treat inflammatory bowel disease through short-term manipulations of the human microbiome may only have a transient effect. Thus, this review is intended to highlight the use of various therapeutic options, including diet, pre- and probiotics, antibiotics and fecal microbiota transplant, to manipulate the microbiome, with specific attention to the alterations made to the microflora along with the duration of impact.

Transcriptome analysis reveals mucin 4 to be highly associated with periodontitis and identifies pleckstrin as a link to systemic diseases

PubMed Central

Lundmark, Anna; Davanian, Haleh; Båge, Tove; Johannsen, Gunnar; Koro, Catalin; Lundeberg, Joakim; Yucel-Lindberg, Tülay

2015-01-01

The multifactorial chronic inflammatory disease periodontitis, which is characterized by destruction of tooth-supporting tissues, has also been implicated as a risk factor for various systemic diseases. Although periodontitis has been studied extensively, neither disease-specific biomarkers nor therapeutic targets have been identified, nor its link with systemic diseases. Here, we analyzed the global transcriptome of periodontitis and compared its gene expression profile with those of other inflammatory conditions, including cardiovascular disease (CVD), rheumatoid arthritis (RA), and ulcerative colitis (UC). Gingival biopsies from 62 patients with periodontitis and 62 healthy subjects were subjected to RNA sequencing. The up-regulated genes in periodontitis were related to inflammation, wounding and defense response, and apoptosis, whereas down-regulated genes were related to extracellular matrix organization and structural support. The most highly up-regulated gene was mucin 4 (MUC4), and its protein product was confirmed to be over-expressed in periodontitis. When comparing the expression profile of periodontitis with other inflammatory diseases, several gene ontology categories, including inflammatory response, cell death, cell motion, and homeostatic processes, were identified as common to all diseases. Only one gene, pleckstrin (PLEK), was significantly overexpressed in periodontitis, CVD, RA, and UC, implicating this gene as an important networking link between these chronic inflammatory diseases. PMID:26686060

Neuroimmunomodulators in neuroborreliosis and Lyme encephalopathy.

PubMed

Eckman, Elizabeth A; Pacheco-Quinto, Javier; Herdt, Aimee R; Halperin, John J

2018-01-11

Lyme encephalopathy, characterized by non-specific neurobehavioral symptoms including mild cognitive difficulties, may occur in patients with systemic Lyme disease and is often mistakenly attributed to CNS infection. Identical symptoms occur in innumerable other inflammatory states and may reflect the effect of systemic immune mediators on the CNS. Multiplex immunoassays were used to characterize the inflammatory profile in serum and CSF from Lyme and non-Lyme patients with a range of symptoms to determine if there are specific markers of active CNS infection (neuroborreliosis), or systemic inflammatory mediators associated with neurobehavioral syndromes. CSF CXCL13 was elevated dramatically in confirmed neuroborreliosis (n=8) and to a lesser extent in possible neuroborreliosis (n=11) and other neuroinflammatory conditions (n=44). Patients with Lyme (n=63) or non-Lyme (n=8) encephalopathy had normal CSF findings, but had elevated serum levels of IL-7, TSLP, IL-17A, IL-17F, and MIP-1α/CCL3. CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody (ITAb) production. However, CXCL13 does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory ITAb, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or following appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors. These markers are also elevated in non-Lyme disease patients experiencing similar symptoms. Our results support that in the absence of CSF abnormalities, neurobehavioral symptoms are associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease. © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Inflammatory Responses, Spirometry, and Quality of Life in Subjects With Bronchiectasis Exacerbations.

PubMed

Guan, Wei-Jie; Gao, Yong-Hua; Xu, Gang; Lin, Zhi-Ya; Tang, Yan; Li, Hui-Min; Lin, Zhi-Min; Jiang, Mei; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

2015-08-01

Bronchiectasis exacerbations are critical events characterized by worsened symptoms and signs (ie, cough frequency, sputum volume, malaise). Our goal was to examine variations in airway and systemic inflammation, spirometry, and quality of life during steady state, bronchiectasis exacerbations, and convalescence (1 week following a 2-week antibiotic treatment) to determine whether potentially pathogenic microorganisms, including Pseudomonas aeruginosa, were associated with poorer conditions during bronchiectasis exacerbations. Peripheral blood and sputum were sampled to detect inflammatory mediators and bacterial densities. Spirometry and quality of life (St George Respiratory Questionnaire [SGRQ]) were assessed during the 3 stages. Forty-eight subjects with bronchiectasis (43.2 ± 14.2 y of age) were analyzed. No notable differences in species and density of potentially pathogenic microorganisms were found during bronchiectasis exacerbations. Except for CXCL8 and tumor necrosis factor alpha (TNF-α), serum inflammation was heightened during bronchiectasis exacerbations and recovered during convalescence. Even though sputum TNF-α was markedly higher during bronchiectasis exacerbations and remained heightened during convalescence, the variations in miscellaneous sputum markers were unremarkable. Bronchiectasis exacerbations were associated with notably higher SGRQ symptom and total scores, which recovered during convalescence. FVC, FEV1, and maximum mid-expiratory flow worsened during bronchiectasis exacerbations (median change from baseline of -2.2%, -0.8%, and -1.3%) and recovered during convalescence (median change from baseline of 0.6%, 0.7%, and -0.7%). Compared with no bacterial isolation, potentially pathogenic microorganism or P. aeruginosa isolation at baseline did not result in poorer clinical condition during bronchiectasis exacerbations. Bronchiectasis exacerbations are characterized by heightened inflammatory responses and poorer quality of life and spirometry, but not by increased bacterial density, which applies for subjects with and without potentially pathogenic microorganism isolation when clinically stable. (ClinicalTrials.gov registration NCT01761214.). Copyright © 2015 by Daedalus Enterprises.

Diagnosis of Atopic Dermatitis: Mimics, Overlaps, and Complications

PubMed Central

Siegfried, Elaine C.; Hebert, Adelaide A.

2015-01-01

Atopic dermatitis (AD) is one of the most common skin diseases affecting infants and children. A smaller subset of adults has persistent or new-onset AD. AD is characterized by pruritus, erythema, induration, and scale, but these features are also typical of several other conditions that can mimic, coexist with, or complicate AD. These include inflammatory skin conditions, infections, infestations, malignancies, genetic disorders, immunodeficiency disorders, nutritional disorders, graft-versus-host disease, and drug eruptions. Familiarity of the spectrum of these diseases and their distinguishing features is critical for correct and timely diagnosis and optimal treatment. PMID:26239454

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

PubMed Central

Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Therapeutic action of ghrelin in a mouse model of colitis.

PubMed

Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

2006-05-01

Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

Impaired SNX9 Expression in Immune Cells during Chronic Inflammation: Prognostic and Diagnostic Implications.

PubMed

Ish-Shalom, Eliran; Meirow, Yaron; Sade-Feldman, Moshe; Kanterman, Julia; Wang, Lynn; Mizrahi, Olga; Klieger, Yair; Baniyash, Michal

2016-01-01

Chronic inflammation is associated with immunosuppression and downregulated expression of the TCR CD247. In searching for new biomarkers that could validate the impaired host immune status under chronic inflammatory conditions, we discovered that sorting nexin 9 (SNX9), a protein that participates in early stages of clathrin-mediated endocytosis, is downregulated as well under such conditions. SNX9 expression was affected earlier than CD247 by the generated harmful environment, suggesting that it is a potential marker sensing the generated immunosuppressive condition. We found that myeloid-derived suppressor cells, which are elevated in the course of chronic inflammation, are responsible for the observed SNX9 reduced expression. Moreover, SNX9 downregulation is reversible, as its expression levels return to normal and immune functions are restored when the inflammatory response and/or myeloid-derived suppressor cells are neutralized. SNX9 downregulation was detected in numerous mouse models for pathologies characterized by chronic inflammation such as chronic infection (Leishmania donovani), cancer (melanoma and colorectal carcinoma), and an autoimmune disease (rheumatoid arthritis). Interestingly, reduced levels of SNX9 were also observed in blood samples from colorectal cancer patients, emphasizing the feasibility of its use as a diagnostic and prognostic biomarker sensing the host's immune status and inflammatory stage. Our new discovery of SNX9 as being regulated by chronic inflammation and its association with immunosuppression, in addition to the CD247 regulation under such conditions, show the global impact of chronic inflammation and the generated immune environment on different cellular pathways in a diverse spectrum of diseases. Copyright © 2015 by The American Association of Immunologists, Inc.

Anti-senescence and Anti-inflammatory Effects of the C-terminal Moiety of PTHrP Peptides in OA Osteoblasts.

PubMed

Platas, Julia; Guillén, Maria Isabel; Gomar, Francisco; Castejón, Miguel Angel; Esbrit, Pedro; Alcaraz, Maria José

2017-05-01

Osteoarthritis (OA) is characterized by degenerative changes in the whole joint leading to physical disability in the elderly population. This condition is associated with altered bone metabolism in subchondral areas suggesting that therapeutic strategies aimed at modifying bone cell metabolism may be of interest. We have investigated the effects of several parathyroid hormone-related protein (PTHrP)-derived peptides (1-37): (N-terminal), (107-111) and (107-139) (C-terminal) on senescence features induced by inflammatory stress in human OA osteoblasts. Incubation of these primary cells with interleukin(IL)-1β led to an increased expression of senescence markers senescence-associated-β-galactosidase activity, γH2AX foci, p16, p21, p53, and caveolin-1. PTHrP (107-111) and PTHrP (107-139) significantly reduced all these parameters. Both peptides decreased the production of IL-6 and prostaglandin E2 which was the consequence of cyclo-oxygenase-2 downregulation. PTHrP (107-139) also reduced tumor necrosis factor-α release. These anti-inflammatory effects would be related to the reduction of nuclear factor-κB activation by both peptides and activator protein-1 by PTHrP (107-139). The three PTHrP peptides favored osteoblastic function although the C-terminal domain of PTHrP was more efficient than its N-terminal domain. Our data support an anti-senescence and anti-inflammatory role for the C-terminal moiety of PTHrP with potential applications in chronic inflammatory conditions such as OA. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Chilean Native Fruit Extracts Inhibit Inflammation Linked to the Pathogenic Interaction Between Adipocytes and Macrophages

PubMed Central

Reyes-Farias, Marjorie; Vasquez, Karla; Ovalle-Marin, Angelica; Fuentes, Francisco; Parra, Claudia; Quitral, Vilma; Jimenez, Paula

2015-01-01

Abstract Obesity is characterized by an increase in the infiltration of monocytes into the adipose tissue, causing an inflammatory condition associated with, for example, the development of insulin resistance. Thus, anti-inflammatory-based treatments could emerge as a novel and interesting approach. It has been reported that Chilean native fruits maqui (Aristotelia chilensis) and calafate (Berberis microphylla) present high contents of polyphenols, which are known for their antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the ability of extracts of these fruits to block the pathogenic interaction between adipocytes and macrophages in vitro and to compare its effect with blueberry (Vaccinium corymbosum) extract treatment, which has been already described to possess several biomedical benefits. RAW264.7 macrophages were treated with 5 μg/mL lipopolysaccharides (LPS), with conditioned media (CM) from fully differentiated 3T3-L1 adipocytes, or in a coculture (CC) with 3T3-L1 adipocytes, in the presence or absence of 100 μM [total polyphenolic content] of each extract for 24 h. The gene expression and secretion profile of several inflammatory markers were evaluated. Nitric oxide secretion induced by LPS, CM, and CC was reduced by the presence of maqui (−12.2%, −45.6%, and −14.7%, respectively) and calafate (−27.6%, −43.9%, and −11.8%, respectively) extracts. Gene expression of inducible nitric oxide synthase and TNF-α was inhibited and of IL-10 was induced by maqui and calafate extract incubation. In conclusion, the extracts of these fruits present important inhibitory-like features over the inflammatory response of the interaction between adipocytes and macrophages, comprising a potential therapeutic tool against comorbidities associated with obesity development. PMID:25302660

Clindamycin phosphate 1.2% and tretinoin 0.025% gel for rosacea: summary of a placebo-controlled, double-blind trial.

PubMed

Freeman, Scott A; Moon, Summer D; Spencer, James M

2012-12-01

Rosacea is a common, chronic, and poorly understood dermatological condition characterized by an inflammatory component composed of papules and pustules and a vascular component composed of flushing and erythema. Current treatment options include topical, systemic, and light-based methods, each of which focuses on either the inflammatory or the vascular component. Retinoids are not routinely indicated as treatment because of the common conception that they would be too inflammatory for the sensitive rosacea patient. However, photodamage may play a role in rosacea and tretinoin is well-known to repair photodamage. Thirty rosacea subjects were enrolled to assess their response to the use of clindamycin phosphate 1.2% and tretinoin 0.025% gel (ZIANA; Medicis Pharmaceutical Corporation, Scottsdale, AZ) for a period of 12 weeks. The results showed a dramatic decrease in pustules and papules without any significant inflammation or overall intolerance. No improvement in facial redness was achieved. Based on our results, more investigation of topical retinoids for rosacea treatment is prudent.

Synthesis and structure-activity relationships of novel cationic lipids with anti-inflammatory and antimicrobial activities.

PubMed

Myint, Melissa; Bucki, Robert; Janmey, Paul A; Diamond, Scott L

2015-07-15

Certain membrane-active cationic steroids are known to also possess both anti-inflammatory and antimicrobial properties. This combined functionality is particularly relevant for potential therapies of infections associated with elevated tissue damage, for example, cystic fibrosis airway disease, a condition characterized by chronic bacterial infections and ongoing inflammation. In this study, six novel cationic glucocorticoids were synthesized using beclomethasone, budesonide, and flumethasone. Products were either monosubstituted or disubstituted, containing one or two steroidal groups, respectively. In vitro evaluation of biological activities demonstrated dual anti-inflammatory and antimicrobial properties with limited cytotoxicity for all synthesized compounds. Budesonide-derived compounds showed the highest degree of both glucocorticoid and antimicrobial properties within their respective mono- and disubstituted categories. Structure-activity analyses revealed that activity was generally related to the potency of the parent glucocorticoid. Taken together, these data indicate that these types of dual acting cationic lipids can be synthesized with the appropriate starting steroid to tailor activities as desired. Copyright © 2015 Elsevier Ltd. All rights reserved.

Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation.

PubMed

Wlodarska, Marta; Luo, Chengwei; Kolde, Raivo; d'Hennezel, Eva; Annand, John W; Heim, Cortney E; Krastel, Philipp; Schmitt, Esther K; Omar, Abdifatah S; Creasey, Elizabeth A; Garner, Ashley L; Mohammadi, Sina; O'Connell, Daniel J; Abubucker, Sahar; Arthur, Timothy D; Franzosa, Eric A; Huttenhower, Curtis; Murphy, Leon O; Haiser, Henry J; Vlamakis, Hera; Porter, Jeffrey A; Xavier, Ramnik J

2017-07-12

Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits. Copyright © 2017 Elsevier Inc. All rights reserved.

[Acute abdomen caused by eosinophilic enteritis: six observations].

PubMed

Martínez-Ubieto, Fernando; Bueno-Delgado, Alvaro; Jiménez-Bernadó, Teresa; Santero Ramírez, María Pilar; Arribas-Del Amo, Dolores; Martínez-Ubieto, Javier

2013-01-01

Eosinophilic enteritis is a rather rare condition characterized by infiltration of the gastrointestinal tract by eosinophils; as a casue of acute abdomen it is really exceptional. The etiology is unclear and its description in the literature is sparse, but associations have been made with collagen vascular disease, inflammatory bowel disease, food allergy and parasitic infections as it was confirmed in one of our pathologic studies. From 1997 to 2011 six cases of eosinophilic enteritis that involved a small bowel segment were diagnosed. A partial resection by an irreversible necrosis was necessary in three of them; in the other three only a biopsy was necessary due to the inflammatory aspect of the affected loop causing the acute abdomen. Eosinophilic enteritis can originate acute abdomen processes where an urgent surgical treatment is necessary. The intraoperative aspect can be from a segment of small bowel with inflammatory signs up to a completely irrecoverable loop, where removing of the affected segment is the correct treatment, which can be done laparoscopically.

Managing heat and immune stress in athletes with evidence-based strategies.

PubMed

Pyne, David B; Guy, Joshua H; Edwards, Andrew M

2014-09-01

Heat and immune stress can affect athletes in a wide range of sports and environmental conditions. The classical thermoregulatory model of heat stress has been well characterized, as has a wide range of practical strategies largely centered on cooling and heat-acclimation training. In the last decade evidence has emerged of an inflammatory pathway that can also contribute to heat stress. Studies are now addressing the complex and dynamic interplay between hyperthermia, the coagulation cascade, and a systemic inflammatory response occurring after transient damage to the gastrointestinal tract. Damage to the intestinal mucosal membrane increases permeability, resulting in leakage of endotoxins into the circulation. Practical strategies that target both thermoregulatory and inflammatory causes of heat stress include precooling; short-term heat-acclimation training; nutritional countermeasures including hydration, energy replacement, and probiotic supplementation; pacing strategies during events; and postevent cooling measures. Cooperation between international, national, and local sporting organizations is required to ensure that heat-management policies and strategies are implemented effectively to promote athletes' well-being and performance.

Synthesis, characterization and molecular docking studies of substituted 4-coumarinylpyrano[2,3-c]pyrazole derivatives as potent antibacterial and anti-inflammatory agents.

PubMed

Chougala, Bahubali M; Samundeeswari, S; Holiyachi, Megharaja; Shastri, Lokesh A; Dodamani, Suneel; Jalalpure, Sunil; Dixit, Sheshagiri R; Joshi, Shrinivas D; Sunagar, Vinay A

2017-01-05

A green, eco-friendly and efficient protocol has been developed and synthesized a series of coumarin based pyrano[2,3-c]pyrazole derivatives (3) by multi-component reaction (MCR). Unexpected 3-coumarinyl-3-pyrazolylpropanoic acids (4) have been isolated by the reaction of compound (3) in acidic conditions. Further, intramolecular cyclization of compounds (4) leads to C 4 C 4 chromons (9) and these compounds were screened for their biological activities using array of techniques. Most of the compounds exhibited promising antibacterial activity, in particular Gram-positive bacteria. The anti-inflammatory assay was evaluated against protein denaturation as well as HRBC membrane stabilization methods and compounds exhibit excellent anti-inflammatory activity in both methods. Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

PubMed Central

Zourdos, Michael C.; Jo, Edward; Ormsbee, Michael J.

2013-01-01

Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation. PMID:24324381

Hepcidin: an emerging biomarker for iron disorders, inflammatory diseases, and infections

NASA Astrophysics Data System (ADS)

Westerman, Mark E.; Olbina, Gordana; Ostland, Vaughn E.; Nemeth, Elizabeta; Ganz, Tomas

2010-04-01

The peptide hormone hepcidin, has emerged as the master regulator of iron homeostasis. Dysregulation of hepcidin is a principal or contributing factor in most genetic and acquired systemic iron disorders, including anemia of inflammation (anemia of chronic disease). Hepcidin maintains healthy blood iron levels by regulating dietary iron absorption and transport from body iron stores to plasma. High serum hepcidin levels observed in chronic and acute inflammatory conditions can cause anemia by limiting plasma iron available for erythropoiesis. Chronically low serum hepcidin levels cause iron-overload and ultimately, accumulation of iron in liver and heart. We recently validated the first immunoassay for serum hepcidin and established the normal ranges in adults. Hepcidin has excellent potential as a biomarker and has a known mechanism of action, good stability, and rapid response to iron stores, inflammatory stimuli, and bacterial infections. Hepcidin can be measured in blood, urine, and saliva, and is generally not measurable in iron deficient/anemic patients and highly elevated in inflammatory diseases and infections. Intrinsic LifeSciences (ILS) is developing second generation hepcidin immunoassays and lateral-flow POC devices for hepcidin, a well characterized multi-purpose biomarker with applications in global health security.

Advances in understanding the pathogenesis of HLH.

PubMed

Usmani, G Naheed; Woda, Bruce A; Newburger, Peter E

2013-06-01

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule-dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi-organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined. © 2013 John Wiley & Sons Ltd.

Antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models

PubMed Central

Hajhashemi, Valiollah; Klooshani, Vahid

2013-01-01

Objective: This study was aimed to examine the antinociceptive and anti-inflammatory effects of Urtica dioica leaf extract in animal models. Materials and Methods: Hydroalcoholic extract of the plant leaves was prepared by percolation method. Male Swiss mice (25-35 g) and male Wistar rats (180-200 g) were randomly distributed in control, standard drug, and three experimental groups (n=6 in each group). Acetic acid-induced writhing, formalin test, and carrageenan-induced paw edema were used to assess the antinociceptive and anti-inflammatory effects. Results: The extract dose-dependently reduced acetic acid-induced abdominal twitches. In formalin test, the extract at any of applied doses (100, 200, and 400 mg/kg) could not suppress the licking behavior of first phase while doses of 200 and 400 mg/kg significantly inhibited the second phase of formalin test. In carrageenan test, the extract at a dose of 400 mg/kg significantly inhibited the paw edema by 26%. Conclusion: The results confirm the folkloric use of the plant extract in painful and inflammatory conditions. Further studies are needed to characterize the active constituents and the mechanism of action of the plant extract. PMID:25050274

Targeting IL-17 AND IL-17D receptors of rheumatoid arthritis using phytocompounds: A Molecular Docking study

NASA Astrophysics Data System (ADS)

Thabitha, A.; Thoufic Ali, A. M. Mohamed; Shweta Kumari, Singh; Rakhi; Swami, Varsha; Mohana Priya, A.; Sajitha Lulu, S.

2017-11-01

Rheumatoid arthritis (RA) is a chronic autoimmune condition of the connective tissue in synovial joints, characterized by inflammation which can lead to bone and cartilage destruction. IL-17 and IL-17D cytokines produced by a number of cell types, primarily promote pro-inflammatory immune responses and negative regulator in fibroblast growth factor signalling. Thus, the promising therapeutic strategies focus on targeting these cytokines, which has led to the identification of effective inhibitors. However, several studies focused on identifying the anti-arthritic potential of natural compounds. Therefore, in the present study we undertook in silico investigations to decipher the anti-inflammatory prospective of phytocompounds by targeting IL-17 and IL-17D cytokines using Patch Dock algorithm. Additionally, IL-17 and IL-17D proteins structure were modelled and validated for molecular docking study. Further, phytocompounds based on anti-inflammatory property were subjected to Lipinski filter and ADMET properties indicated that all of these compounds showed desirable drug-like criteria. The outcome of this investigation sheds light on the anti-inflammatory mechanism of phytocompounds by targeting IL-17 and IL-D for effective treatment of RA.

The Histological and Immunohistochemical Features of the Skin Lesions in CANDLE Syndrome

PubMed Central

Torrelo, Antonio; Colmenero, Isabel; Requena, Luis; Paller, Amy S.; Ramot, Yuval; Lee, Chyi-Chia Richard; Vera, Angel; Zlotogorski, Abraham; Goldbach-Mansky, Raphaela; Kutzner, Heinz

2015-01-01

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a newly characterized autoinflammatory disorder, caused by mutations in PSMB8. It is characterized by early-onset fevers, accompanied by a widespread, violaceous and often annular, cutaneous eruption. While the exact pathogenesis of this syndrome is still obscure, it is postulated that the inflammatory disease manifestations stem from excess secretion of interferons. Based on preliminary blood cytokine and gene expression studies, the signature seems to come mostly from type I interferons, which are proposed to lead to the recruitment of immature myeloid cells into the dermis and subcutis. In this study, we systematically analyzed skin biopsies from 6 CANDLE syndrome patients by routine histopathology and immunohistochemistry methods. Skin lesions showed the presence of extensive mixed dermal and subcutaneous inflammatory infiltrate, composed of mononuclear cells, atypical myeloid cells, neutrophils, eosinophils and some mature lymphocytes. Positive LEDER and myeloperoxidase staining supported the presence of myeloid cells. Positive CD68/PMG1 and CD163 staining confirmed the existence of histiocytes and monocytic macrophages in the inflammatory infiltrate. CD123 staining was positive, demonstrating the presence of plasmacytoid dendritic cells. Uncovering the unique histopathologic and immunohistochemical features of CANDLE syndrome provides tools for rapid and specific diagnosis of this disorder as well as further insight into the pathogenesis of this severe, life-threatening condition. PMID:26091509

Liquid Crystalline Systems Based on Glyceryl Monooleate and Penetration Enhancers for Skin Delivery of Celecoxib: Characterization, In Vitro Drug Release, and In Vivo Studies.

PubMed

Dante, Mariane de Cássia Lima; Borgheti-Cardoso, Livia Neves; Fantini, Marcia Carvalho de Abreu; Praça, Fabíola Silva Garcia; Medina, Wanessa Silva Garcia; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

2018-03-01

Celecoxib (CXB) is a widely used anti-inflammatory drug that also acts as a chemopreventive agent against several types of cancer, including skin cancer. As the long-term oral administration of CXB has been associated with severe side effects, the skin delivery of this drug represents a promising alternative for the treatment of skin inflammatory conditions and chemoprevention of skin cancer. We prepared and characterized liquid crystalline systems based on glyceryl monooleate and water containing penetration enhancers which were primarily designed to promote skin delivery of CXB. Analysis of their phase behavior revealed the formation of cubic and hexagonal phases depending on the systems' composition. The systems' structure and composition markedly affected the in vitro CXB release profile. Oleic acid reduced CXB release rate, but association oleic acid/propylene glycol increased the drug release rate. The developed systems significantly reduced inflammation in an aerosil-induced rat paw edema model. The systems' composition and liquid crystalline structure influenced their anti-inflammatory potency. Cubic phase systems containing oleic acid/propylene glycol association reduced edema in a sustained manner, indicating that they modulate CXB release and permeation. Our findings demonstrate that the developed liquid crystalline systems are potential carriers for the skin delivery of CXB. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

The Neutrophil’s Choice: Phagocytose vs Make Neutrophil Extracellular Traps

PubMed Central

Manfredi, Angelo A.; Ramirez, Giuseppe A.; Rovere-Querini, Patrizia; Maugeri, Norma

2018-01-01

Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo via phagocytosis or by releasing neutrophil extracellular traps (NETs) outside the cell, thus modifying and alerting the environment and bystander leukocytes. The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be “poised” in an unresponsive state. Environmental conditions, the metabolic, adhesive and activation state of the phagocyte, and the size of and signals associated with the tethered phagocytic cargo influence the choice of the neutrophils, prompting either phagocytic clearance or the generation of NETs. The choice is dichotomic and apparently irreversible. Defects in phagocytosis may foster the intravascular generation of NETs, thus promoting vascular inflammation and morbidities associated with diseases characterized by defective phagocytic clearance, such as systemic lupus erythematosus. There is a strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes. PMID:29515586

Interleukin-6 responses to water immersion therapy after acute exercise heat stress: a pilot investigation.

PubMed

Lee, Elaine C; Watson, Greig; Casa, Douglas; Armstrong, Lawrence E; Kraemer, William; Vingren, Jakob L; Spiering, Barry A; Maresh, Carl M

2012-01-01

Cold-water immersion is the criterion standard for treatment of exertional heat illness. Cryotherapy and water immersion also have been explored as ergogenic or recovery aids. The kinetics of inflammatory markers, such as interleukin-6 (IL-6), during cold-water immersion have not been characterized. To characterize serum IL-6 responses to water immersion at 2 temperatures and, therefore, to initiate further research into the multidimensional benefits of immersion and the evidence-based selection of specific, optimal immersion conditions by athletic trainers. Controlled laboratory study. Human performance laboratory Patients or Other Participants: Eight college-aged men (age = 22 ± 3 years, height = 1.76 ± 0.08 m, mass = 77.14 ± 9.77 kg, body fat = 10% ± 3%, and maximal oxygen consumption = 50.48 ± 4.75 mL·kg(-1) min(-1)). Participants were assigned randomly to receive either cold (11.70°C ± 2.02°C, n = 4) or warm (23.50°C ± 1.00°C, n = 4) water-bath conditions after exercise in the heat (temperature = 37°C, relative humidity = 52%) for 90 minutes or until volitional cessation. Whole-body cooling rates were greater in the cold water-bath condition for the first 6 minutes of water immersion, but during the 90-minute, postexercise recovery, participants in the warm and cold water-bath conditions experienced similar overall whole-body cooling. Heart rate responses were similar for both groups. Participants in the cold water-bath condition experienced an overall slight increase (30.54% ± 77.37%) in IL-6 concentration, and participants in the warm water-bath condition experienced an overall decrease (-69.76% ± 15.23%). We have provided seed evidence that cold-water immersion is related to subtle IL-6 increases from postexercise values and that warmer water-bath temperatures might dampen this increase. Further research will elucidate any anti-inflammatory benefit associated with water-immersion treatment and possible multidimensional uses of cooling therapies.

Total glucosides of paeony (TGP) inhibits the production of inflammatory cytokines in oral lichen planus by suppressing the NF-κB signaling pathway.

PubMed

Wang, Yanni; Zhang, Han; Du, Guanhuan; Wang, Yufeng; Cao, Tianyi; Luo, Qingqiong; Chen, Junjun; Chen, Fuxiang; Tang, Guoyao

2016-07-01

Total glucosides of paeony (TGP) is a bioactive compound extracted from paeony roots and has been widely used to ameliorate inflammation in several autoimmune and inflammatory diseases. However, the anti-inflammatory effect of TGP on oral lichen planus (OLP), a chronic inflammatory oral condition characterized by T-cell infiltration and abnormal epithelial keratinization cycle remains unclear. In this study, we found that TLR4 was highly expressed and activation of the NF-κB signaling pathway was obviously observed in the OLP tissues. Moreover, there was significant higher mRNA expression of inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in OLP keratinocytes than normal oral epithelial keratinocytes. With the help of the cell culture model by stimulating the keratinocyte HaCaT cells with lipopolysaccharides (LPS), we mimicked the local inflammatory environment of OLP. And we further confirmed that TGP could inhibit LPS-induced production of IL-6 and TNF-α in HaCaT cells via a dose-dependent manner. TGP treatment decreased the phosphorylation of IκBα and NF-κB p65 proteins, thus leading to less nuclear translocation of NF-κB p65 in HaCaT cells. Therefore, our data suggested that TGP may be a new potential candidate for the therapy of OLP. Copyright © 2016 Elsevier B.V. All rights reserved.

Mesenchymal Stem Cell Derived Secretome and Extracellular Vesicles for Acute Lung Injury and Other Inflammatory Lung Diseases

PubMed Central

Monsel, Antoine; Zhu, Ying-gang; Gudapati, Varun; Lim, Hyungsun; Lee, Jae W.

2017-01-01

Introduction Acute respiratory distress syndrome is a major cause of respiratory failure in critically ill patients. Despite extensive research into its pathophysiology, mortality remains high. No effective pharmacotherapy exists. Based largely on numerous preclinical studies, administration of mesenchymal stem or stromal cell (MSC) as a therapeutic for acute lung injury holds great promise, and clinical trials are currently underway. However, concern for the use of stem cells, specifically the risk of iatrogenic tumor formation, remains unresolved. Accumulating evidence now suggest that novel cell-free therapies including MSC-derived conditioned medium and extracellular vesicles released from MSCs might constitute compelling alternatives. Areas covered The current review summarizes the preclinical studies testing MSC conditioned medium and/or MSC extracellular vesicles as treatment for acute lung injury and other inflammatory lung diseases. Expert opinion While certain logistical obstacles limit the clinical applications of MSC conditioned medium such as the volume required for treatment, the therapeutic application of MSC extracellular vesicles remains promising, primarily due to ability of extracellular vesicles to maintain the functional phenotype of the parent cell. However, utilization of MSC extracellular vesicles will require large-scale production and standardization concerning identification, characterization and quantification. PMID:27011289

Preparation, characterization, and in vitro anti-inflammatory evaluation of novel water soluble kamebakaurin/hydroxypropyl-β-cyclodextrin inclusion complex

NASA Astrophysics Data System (ADS)

Raza, Aun; Sun, Huifang; Bano, Shumaila; Zhao, Yingying; Xu, Xiuquan; Tang, Jian

2017-02-01

To enhance the aqueous solubility of kamebakaurin (KA), it was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, the interaction KA with HP-β-CD and their inclusion complex behavior were determined by different characterization techniques such as UV-vis, 1H NMR, FT-IR, PXRD and SEM. All the characterization information proved the development of inclusion complex KA/HP-β-CD, and this inclusion complex demonstrated discriminable spectroscopic characteristics and properties from free compound KA. The results demonstrated that the water solubility of KA was remarkably increased in the presence of HP-β-CD. Furthermore, in vitro anti-inflammatory study showed that inclusion complex KA/HP-β-CD maintained the anti-inflammatory effect of KA. These results demonstrate that HP-β-CD will be promisingly employed in the application of water-insoluble anti-inflammatory phytochemicals such as KA.

A novel murine model of rhinoscleroma identifies Mikulicz cells, the disease signature, as IL-10 dependent derivatives of inflammatory monocytes

PubMed Central

Fevre, Cindy; Almeida, Ana S; Taront, Solenne; Pedron, Thierry; Huerre, Michel; Prevost, Marie-Christine; Kieusseian, Aurélie; Cumano, Ana; Brisse, Sylvain; Sansonetti, Philippe J; Tournebize, Régis

2013-01-01

Rhinoscleroma is a human specific chronic disease characterized by the formation of granuloma in the airways, caused by the bacterium Klebsiella pneumoniae subspecies rhinoscleromatis, a species very closely related to K. pneumoniae subspecies pneumoniae. It is characterized by the appearance of specific foamy macrophages called Mikulicz cells. However, very little is known about the pathophysiological processes underlying rhinoscleroma. Herein, we characterized a murine model recapitulating the formation of Mikulicz cells in lungs and identified them as atypical inflammatory monocytes specifically recruited from the bone marrow upon K. rhinoscleromatis infection in a CCR2-independent manner. While K. pneumoniae and K. rhinoscleromatis infections induced a classical inflammatory reaction, K. rhinoscleromatis infection was characterized by a strong production of IL-10 concomitant to the appearance of Mikulicz cells. Strikingly, in the absence of IL-10, very few Mikulicz cells were observed, confirming a crucial role of IL-10 in the establishment of a proper environment leading to the maturation of these atypical monocytes. This is the first characterization of the environment leading to Mikulicz cells maturation and their identification as inflammatory monocytes. PMID:23554169

Corneal reepithelialization and anti-inflammatory agents.

PubMed Central

Srinivasan, B D

1982-01-01

These studies have demonstrated that nonsteroidal anti-inflammatory agents (cyclooxygenase and lipoxygenase inhibitors) can inhibit PMN arrival in the tear fluid following corneal injury but do not inhibit the reepithelialization either by corneal epithelial cells or by conjunctival epithelial cells. Therefore, they can be used safely in ocular inflammatory conditions even when corneal epithelial defects are present. Corticosteroids, on the other hand, inhibit reepithelialization by conjunctival epithelial cells and not by corneal epithelial cells in the doses tested. This inhibition does not occur with pretreatment prior to injury, suggesting that corticosteroids can be used clinically in conditions that have intact corneal epithelium without fear of slowing down wound healing should epithelial defects occur when not on steroid therapy. Furthermore, the steroid inhibition is temporary since there is a breakthrough in steroid inhibition with time, and occurs only if the steroids have been used shortly after deepithelialization. The steroid inhibition can be reversed by specific steroid antagonist, indicating that the steroid effect is mediated through specific receptors. An exciting and new hypothesis proposes that corticosteroids induce the formation of an inhibitory protein that inhibits the phospholipase enzyme to cause a block in arachidonic acid release from cell membranes. This mechanism of action may also be prevalent in the steroid effect on corneal reepithelialization, and experiments are under way to isolate this inhibitory protein from steroid-treated conjunctival epithelium. This isolation and pharmacologic characterization of this inhibitory protein is of obvious advantage to the field of ophthalmic therapeutics since this protein may have the anti-inflammatory potential of the steroids without their steroid sideeffects. Images FIGURE 3 a FIGURE 3 b PMID:6763806

De novo tetrahydrobiopterin biosynthesis is impaired in the inflammed striatum of parkin(-/-) mice.

PubMed

de Paula Martins, Roberta; Glaser, Viviane; Aguiar, Aderbal S; de Paula Ferreira, Priscila Maximiliano; Ghisoni, Karina; da Luz Scheffer, Débora; Lanfumey, Laurence; Raisman-Vozari, Rita; Corti, Olga; De Paul, Ana Lucia; da Silva, Rodrigo Augusto; Latini, Alexandra

2018-06-01

Parkinson's disease (PD), the second-most prevalent neurodegenerative disease, is primarily characterized by neurodegeneration in the substantia nigra pars compacta, resulting in motor impairment. Loss-of-function mutations in parkin are the major cause of the early onset familial form of the disease. Although rodents deficient in parkin (parkin (-/-) ) have some dopaminergic system dysfunction associated with central oxidative stress and energy metabolism deficiencies, these animals only display nigrostriatal pathway degeneration under inflammatory conditions. This study investigated the impact of the inflammatory stimulus induced by lypopolisaccharide (LPS) on tetrahydrobiopterin (BH4) synthesizing enzymes (de novo and salvage pathways), since this cofactor is essential for dopamine synthesis. The mitochondrial content and architecture was investigated in the striatum of LPS-exposed parkin (-/-) mice. As expected, the LPS (0.33 mg/kg; i.p.) challenge compromised spontaneous locomotion and social interaction with juvenile parkin (-/-) and WT mice. Moreover, the genotype impacted the kinetics of the investigation of the juvenile. The inflammatory scenario did not induce apparent changes in mitochondrial ultrastructure; however, it increased the quantity of mitochondria, which were of smaller size, and provoked the perinuclear distribution of the organelle. Furthermore, the BH4 de novo biosynthetic pathway failed to be up-regulated in the LPS challenge, a well-known stimulus for its activation. The LPS treatment increased sepiapterin reductase (SPR) expression, suggesting compensation by the salvage pathway. This might indicate that dopamine synthesis is compromised in parkin (-/-) mice under inflammatory conditions. Finally, this scenario impaired the striatal expression of the transcription factor BDNF, possibly favoring cell death. © 2018 International Federation for Cell Biology.

Inflammation, aging, and adiposity: implications for physical therapists.

PubMed

Addison, Odessa; LaStayo, Paul C; Dibble, Leland E; Marcus, Robin L

2012-01-01

Physical therapists treat older individuals, characterized as both a needy and expanding population. Frailty, a predisability condition with links to chronic inflammatory conditions, is estimated to affect 7% of individuals older than 60 years and 40% of people older than 80 years. Chronic inflammation is one of the most important physiologic correlates of the frailty syndrome and high levels of proinflammatory cytokines, related to both aging and increasing adiposity in older individuals are related to an increased risk of mortality, sarcopenia, reduced muscle strength and decreased mobility. The purpose of this narrative review is to inform the physical therapist of the effects of aging and increasing adiposity on chronic inflammation and the association of inflammation with muscle loss, strength, and mobility impairments in older adults; and to review the current evidence to provide clinical recommendations on physical activity and exercise regimes that may mitigate chronic inflammation in older adults. As physical therapists help manage and treat an increasingly older population, understanding how the inflammatory milieu changes with aging and increasing adiposity and how these changes can be impacted by physical therapists via exercise and physical activity is critical. Exercise is a potent preventive intervention strategy and countermeasure for chronic inflammation and adiposity. Exercise can also benefit the frail older individual by combating the negative effects of chronic inflammation and optimally balancing the production of pro and anti-inflammatory cytokines. In addition to providing an anti-inflammatory environment within muscle to mitigate the effects of chronic inflammation, exercise has the added benefit of improving muscle mass and function and decreasing adiposity in older adults.

Characterization of culture filtrate proteins Rv1197 and Rv1198 of ESAT-6 family from Mycobacterium tuberculosis H37Rv.

PubMed

Pandey, Himanshu; Tripathi, Sarita; Srivastava, Kanchan; Tripathi, Dinesh K; Srivastava, Mrigank; Kant, Surya; Srivastava, Kishore K; Arora, Ashish

2017-02-01

We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively. Rv1197 and Rv1198 strongly interact to form a heterodimeric complex under reducing conditions, which is characterized by a dissociation constant of 97×10 -9 M and melting temperature, Tm, of 50.5°C. Strong humoral responses to Rv1197, Rv1198, CFP-10 and MoaC1 (Rv3111) antigens were found in Indian patients with active pulmonary tuberculosis (n=44), in comparison to non-infected healthy individuals (n=20). The seroreactivity to Rv1198 was characterized by a sensitivity of 75% and specificity of 90%. In BALB/c mice, immunization with Rv1198-FIA induced a pro-inflammatory response with elevated levels of TNF and IL-6, along with low induction of IFN-γ, IL-2 and IL-10, but no induction of IL-4. Rv1197 and Rv1198 form a stable complex, which is regulated by the redox state of Rv1198. Rv1198 is immunogenic with highly specific seroreactivity towards TB patients' serum. Rv1198 elicits a pro-inflammatory recall response in immunized mice. This study characterizes the interaction of Rv1197 and Rv1198, and establishes the immunogenic nature of Rv1198. Copyright © 2016 Elsevier B.V. All rights reserved.

Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE

PubMed Central

Donegà, Matteo; Giusto, Elena; Cossetti, Chiara; Schaeffer, Julia; Pluchino, Stefano

2014-01-01

Neural stem/precursor cells (NPCs) are a promising stem cell source for transplantation approaches aiming at brain repair or restoration in regenerative neurology. This directive has arisen from the extensive evidence that brain repair is achieved after focal or systemic NPC transplantation in several preclinical models of neurological diseases. These experimental data have identified the cell delivery route as one of the main hurdles of restorative stem cell therapies for brain diseases that requires urgent assessment. Intraparenchymal stem cell grafting represents a logical approach to those pathologies characterized by isolated and accessible brain lesions such as spinal cord injuries and Parkinson's disease. Unfortunately, this principle is poorly applicable to conditions characterized by a multifocal, inflammatory and disseminated (both in time and space) nature, including multiple sclerosis (MS). As such, brain targeting by systemic NPC delivery has become a low invasive and therapeutically efficacious protocol to deliver cells to the brain and spinal cord of rodents and nonhuman primates affected by experimental chronic inflammatory damage of the central nervous system (CNS). This alternative method of cell delivery relies on the NPC pathotropism, specifically their innate capacity to (i) sense the environment via functional cell adhesion molecules and inflammatory cytokine and chemokine receptors; (ii) cross the leaking anatomical barriers after intravenous (i.v.) or intracerebroventricular (i.c.v.) injection; (iii) accumulate at the level of multiple perivascular site(s) of inflammatory brain and spinal cord damage; and (i.v.) exert remarkable tissue trophic and immune regulatory effects onto different host target cells in vivo. Here we describe the methods that we have developed for the i.v. and i.c.v. delivery of syngeneic NPCs in mice with experimental autoimmune encephalomyelitis (EAE), as model of chronic CNS inflammatory demyelination, and envisage the systemic stem cell delivery as a valuable technique for the selective targeting of the inflamed brain in regenerative neurology. PMID:24798882

Physical versus psychological social stress in male rats reveals distinct cardiovascular, inflammatory and behavioral consequences

PubMed Central

Padi, Akhila R.; Moffitt, Casey M.; Wilson, L. Britt; Wood, Christopher S.; Wood, Susan K.

2017-01-01

Repeated exposure to social stress can precipitate the development of psychosocial disorders including depression and comorbid cardiovascular disease. While a major component of social stress often encompasses physical interactions, purely psychological stressors (i.e. witnessing a traumatic event) also fall under the scope of social stress. The current study determined whether the acute stress response and susceptibility to stress-related consequences differed based on whether the stressor consisted of physical versus purely psychological social stress. Using a modified resident-intruder paradigm, male rats were either directly exposed to repeated social defeat stress (intruder) or witnessed a male rat being defeated. Cardiovascular parameters, behavioral anhedonia, and inflammatory cytokines in plasma and the stress-sensitive locus coeruleus were compared between intruder, witness, and control rats. Surprisingly intruders and witnesses exhibited nearly identical increases in mean arterial pressure and heart rate during acute and repeated stress exposures, yet only intruders exhibited stress-induced arrhythmias. Furthermore, re-exposure to the stress environment in the absence of the resident produced robust pressor and tachycardic responses in both stress conditions indicating the robust and enduring nature of social stress. In contrast, the long-term consequences of these stressors were distinct. Intruders were characterized by enhanced inflammatory sensitivity in plasma, while witnesses were characterized by the emergence of depressive-like anhedonia, transient increases in systolic blood pressure and plasma levels of tissue inhibitor of metalloproteinase. The current study highlights that while the acute cardiovascular responses to stress were identical between intruders and witnesses, these stressors produced distinct differences in the enduring consequences to stress, suggesting that witness stress may be more likely to produce long-term cardiovascular dysfunction and comorbid behavioral anhedonia while exposure to physical stressors may bias the system towards sensitivity to inflammatory disorders. PMID:28241050

Factors secreted from dental pulp stem cells show multifaceted benefits for treating acute lung injury in mice.

PubMed

Wakayama, Hirotaka; Hashimoto, Naozumi; Matsushita, Yoshihiro; Matsubara, Kohki; Yamamoto, Noriyuki; Hasegawa, Yoshinori; Ueda, Minoru; Yamamoto, Akihito

2015-08-01

Acute respiratory distress syndrome (ARDS) is a severe inflammatory disorder characterized by acute respiratory failure, resulting from severe, destructive lung inflammation and irreversible lung fibrosis. We evaluated the use of stem cells derived from human exfoliated deciduous teeth (SHEDs) or SHED-derived serum-free conditioned medium (SHED-CM) as treatments for bleomycin (BLM)-induced mice acute lung injury (ALI), exhibiting several pathogenic features associated with the human disease ARDS. Mice with BLM-induced ALI with or without SHED or SHED-CM treatment were examined for weight loss and survival. The lung tissue was characterized by histological and real-time quantitative polymerase chain reaction analysis. The effects of SHED-CM on macrophage differentiation in vitro were also assessed. A single intravenous administration of either SHEDs or SHED-CM attenuated the lung injury and weight loss in BLM-treated mice and improved their survival rate. Similar recovery levels were seen in the SHEDs and SHED-CM treatment groups, suggesting that SHED improves ALI by paracrine mechanisms. SHED-CM contained multiple therapeutic factors involved in lung-regenerative mechanisms. Importantly, SHED-CM attenuated the BLM-induced pro-inflammatory response and generated an anti-inflammatory/tissue-regenerating environment, accompanied by the induction of anti-inflammatory M2-like lung macrophages. Furthermore, SHED-CM promoted the in vitro differentiation of bone marrow-derived macrophages into M2-like cells, which expressed high levels of Arginase1, CD206 and Ym-1. Our results suggest that SHED-secreted factors provide multifaceted therapeutic effects, including a strong M2-inducing activity, for treating BLM-induced ALI. This work may open new avenues for research on stem cell-based ARDS therapies. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Decreased Bacterial Diversity Characterizes an Altered Gut Microbiota in Psoriatic Arthritis and Resembles Dysbiosis of Inflammatory Bowel Disease

PubMed Central

Scher, Jose U.; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M.; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G.; Littman, Dan R.; Abramson, Steven B.

2014-01-01

Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). Methods High-throughput 16S rRNA pyrosequencing was utilized to compare community composition of gut microbiota in PsA patients (n=16), subjects with psoriasis of the skin (Ps) (n=15) and healthy, matched-controls (n=17). Samples were further assessed for the presence and levels of fecal and serum secretory immunoglobulin A (sIgA), pro-inflammatory proteins and fatty-acids. Results The gut microbiota observed in PsA and Ps patients was less diverse when compared to healthy controls. These could be attributed to the reduced presence of several taxa. While both groups showed a relative decrease in Coprococcus spp., PsA samples were characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA and a decrease in receptor activator of nuclear factor kappa-B ligand (RANKL) levels. Fatty acid analysis revealed low levels of hexanoate and heptanoate in PsA and Ps patients. Conclusion PsA and Ps patients had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that published for patients with IBD and was associated with changes in specific inflammatory proteins unique to this group, and distinct from Ps and controls. Thus, the role of gut microbiota in the continuum of Ps-PsA pathogenesis and the associated immune response merits further study. PMID:25319745

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer.

PubMed

Roy, Lopamudra Das; Ghosh, Sriparna; Pathangey, Latha B; Tinder, Teresa L; Gruber, Helen E; Mukherjee, Pinku

2011-08-22

Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in arthritic PyV MT mice. This was further substantiated by treatment with celecoxib, an anti-inflammatory drug + αIL-17 antibody that significantly reduced the secondary metastasis to lung and bone. The data generated not only reveal the underlying mechanism of high susceptibility to bone and lung metastasis in an arthritic condition but our combination therapies may lead to treatment modalities that will be capable of reducing tumor burden, and preventing relapse and metastasis in arthritic patients with breast cancer.

Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

PubMed Central

2011-01-01

Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in arthritic PyV MT mice. This was further substantiated by treatment with celecoxib, an anti-inflammatory drug + αIL-17 antibody that significantly reduced the secondary metastasis to lung and bone. Conclusions The data generated not only reveal the underlying mechanism of high susceptibility to bone and lung metastasis in an arthritic condition but our combination therapies may lead to treatment modalities that will be capable of reducing tumor burden, and preventing relapse and metastasis in arthritic patients with breast cancer. PMID:21859454

A Case of Atrophia Maculosa Varioliformis Cutis

PubMed Central

Kim, Dong Hyun; Lee, Seung Min; Kim, Tae Yoon

2008-01-01

Atrophia maculosa varioliformis cutis is a rare disease that was first described by Heidingsfeld in 1918. It is characterized by an idiopathic, non-inflammatory macular atrophy that typically occurs on the face in young individuals. Despite its association with some diseases, the etiopathogenesis of this entity remains unknown. After consideration of the differential diagnosis criteria for idiopathic atrophic conditions, we report a case for a 40-year-old Korean male whose past medical history was suggestive of atrophia maculosa varioliformis cutis. PMID:27303204

A Case of Atrophia Maculosa Varioliformis Cutis.

PubMed

Kim, Dong Hyun; Lee, Seung Min; Kim, Tae Yoon; Yoon, Moon Soo

2008-12-01

Atrophia maculosa varioliformis cutis is a rare disease that was first described by Heidingsfeld in 1918. It is characterized by an idiopathic, non-inflammatory macular atrophy that typically occurs on the face in young individuals. Despite its association with some diseases, the etiopathogenesis of this entity remains unknown. After consideration of the differential diagnosis criteria for idiopathic atrophic conditions, we report a case for a 40-year-old Korean male whose past medical history was suggestive of atrophia maculosa varioliformis cutis.

GPR120 in adipocytes has differential roles in the production of pro-inflammatory adipocytokines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Arif Ul, E-mail: ahasan@med.kagawa-u.ac.jp; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793; Ohmori, Koji

How nutritional excess leads to inflammatory responses in metabolic syndrome is not well characterized. Here, we evaluated the effects of ω-3 polyunsaturated fatty acid specific G-protein coupled receptor 120 (GPR120) activation on inflammatory pathways in adipocytes, and the influence of this process on macrophage migration. Using 3T3-L1 adipocytes, we found that agonizing GPR120 using its synthetic ligand, GSK137647, attenuated both basal and lipopolysaccharide-induced production of interleukin-6 (IL-6) and C-C motif chemokine ligand 2 (CCL2). Moreover, the intervention reduced the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and nuclear translocation of nuclear factor kappa-B p65 subunit (p65). Furthermore, themore » silencing of GPR120 itself reduced IL-6 and CCL2 mRNA expression. Inhibition of protein kinase C (PKC) augmented the down-regulatory effect of GSK137647 on IL-6 and CCL2 mRNA. Using a luciferase assay to measure promoter activity of the IL-6 gene in mouse embryonic fibroblasts, we demonstrated that exogenous transfection of GPR120 alone reduced the promoter activity, which was augmented by GSK137647. Inhibition of PKC further reduced the promoter activity. Nevertheless, RAW 264.7 macrophages grown in conditioned medium collected from GSK137647-treated adipocytes attenuated the expressions of matrix metalloproteinases-9 and -3, and tissue inhibitor of metalloproteinase-1. Conditioned medium also inhibited the lipopolysaccharide-induced migration of these macrophages. Taken together, these findings provide critical evidence that although GPR120 is associated with a PKC-mediated pro-inflammatory pathway, the direct inhibitory effects of GPR120 on the nuclear factor kappa B pathway are anti-inflammatory. Moreover, GPR120 activity can attenuate the adipocyte-mediated enhanced production of extracellular matrix-modulating factors in macrophages and can reduce their migration by a paracrine mechanism. - Highlights: • Agonizing GPR120 differentially regulates the pro-inflammatory adipocytokines. • Agonizing GPR120 in adipocytes attenuates NF-κB mediated IL-6 and CCL2 production. • Agonizing GPR120 concomitantly triggers a PKC mediated pro-inflammatory pathway. • However, the resulted effect in adipocytes remains anti-inflammatory. • Agonizing GPR120 in adipocytes reduces macrophage migration in a paracrine manner.« less

Retroperitoneal fibrosis: case series of five patients and review of the literature.

PubMed

Shiber, Shacahf; Eliakim-Raz, Noa; Yair, Molad

2016-01-01

Chronic periaortitis (CP) is an umbrella term used to describe a group of nosologically allied conditions that include idiopathic retroperitoneal fibrosis (Ormond's disease), inflammatory abdominal aortic aneurysm, and perianeurysmal retroperitoneal fibrosis. Retroperitoneal fibrosis encompasses a range of diseases characterized by the presence of a fibro-inflammatory tissue, which usually surrounds the abdominal aorta and the iliac arteries and extends into the retroperitoneum to envelop neighboring structures-ureters. Retroperitoneal fibrosis is generally idiopathic, but can also be secondary to the use of certain drugs, malignant diseases, infections, and surgery. Here we describe a 5 years follow-up (2006-2011) of 5 patients admitted to our hospital with symptoms, laboratory, imaging and pathologic finding compatible with retroperitoneal fibrosis. We review our clinical course of our patient with respect to the literature. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Pediatric head and neck masses.

PubMed

Gujar, Sachin; Gandhi, Dheeraj; Mukherji, Suresh K

2004-04-01

Most neck masses in the pediatric head and neck region are benign. Congenital, developmental, and inflammatory lesions make up most of the masses in the pediatric head and neck. For example, neck masses due to inflammatory lymphadenitis are common in children because of the frequency of upper respiratory tract infections. Although many of the malignant tumors in children are found in the head and neck, they account for only a small portion of the neck masses. The choice of the imaging modality is based on a number of factors, several of which are unique to the pediatric population. Although the bulk of disease entities are adequately evaluated by CT, MRI can provide additional vital information in many cases. MRI provides better soft tissue characterization than CT, has multiplanar capabilities. In this article, we will attempt to provide an overview of conditions that present as neck masses.

A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder

PubMed Central

Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H. Henry; Mysorekar, Indira U.

2016-01-01

Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. PMID:27029431

The Contribution of the Airway Epithelial Cell to Host Defense.

PubMed

Stanke, Frauke

2015-01-01

In the context of cystic fibrosis, the epithelial cell has been characterized in terms of its ion transport capabilities. The ability of an epithelial cell to initiate CFTR-mediated chloride and bicarbonate transport has been recognized early as a means to regulate the thickness of the epithelial lining fluid and recently as a means to regulate the pH, thereby determining critically whether or not host defense proteins such as mucins are able to fold appropriately. This review describes how the epithelial cell senses the presence of pathogens and inflammatory conditions, which, in turn, facilitates the activation of CFTR and thus directly promotes pathogens clearance and innate immune defense on the surface of the epithelial cell. This paper summarizes functional data that describes the effect of cytokines, chemokines, infectious agents, and inflammatory conditions on the ion transport properties of the epithelial cell and relates these key properties to the molecular pathology of cystic fibrosis. Recent findings on the role of cystic fibrosis modifier genes that underscore the role of the epithelial ion transport in host defense and inflammation are discussed.

Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease.

PubMed

Kuhlman, Kate Ryan; Chiang, Jessica J; Horn, Sarah; Bower, Julienne E

2017-09-01

Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Oxidative Stress and Membrane Transport Systems during Endometriosis: A Fresh Look at a Busy Corner

PubMed Central

Capriglione, Stella; Peterlunger, Isabel; La Rosa, Valentina Lucia; Vitagliano, Amerigo; Noventa, Marco; Valenti, Gaetano; Sapia, Fabrizio; Angioli, Roberto; Lopez, Salvatore; Sarpietro, Giuseppe; Rossetti, Diego; Zito, Gabriella

2018-01-01

Endometriosis is a condition characterized by the presence of endometrial tissue outside the uterine cavity, leading to a chronic inflammatory reaction. It is one of the most widespread gynecological diseases with a 10–15% prevalence in the general female population, rising up to 30–45% in patients with infertility. Although it was first described in 1860, its etiology and pathogenesis are still unclear. It is now accepted that inflammation plays a central role in the development and progression of endometriosis. In particular, it is marked by an inflammatory process associated with the overproduction of an array of inflammatory mediators such as prostaglandins, metalloproteinases, cytokines, and chemokines. In addition, the growth and adhesion of endometrial cells in the peritoneal cavity due to reactive oxygen species (ROS) and free radicals lead to disease onset, its ensuing symptoms—among which pain and infertility. The aim of our review is to evaluate the role of oxidative stress and ROS in the pathogenesis of endometriosis and the efficacy of antioxidant therapy in the treatment and mitigation of its symptoms. PMID:29743986

Treating metabolic syndrome's metaflammation with low level light therapy: preliminary results

NASA Astrophysics Data System (ADS)

Yoshimura, Tania M.; Kato, Ilka T.; Deana, Alessandro M.; Ribeiro, Martha S.

2014-02-01

Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 mice were submitted to a high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power, ~6 J/cm2 fluence, ~19 mW/cm2 fluence rate). Before and during treatment, blood was sampled either from the retroorbital plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. So far our results indicate no alterations on these metabolic parameters after LLLT. For further investigations, blood was collected for plasma inflammatory cytokine quantification and fresh ex vivo samples of liver and intra-abdominal adipose tissue were harvested for immunohistochemistry purposes.

Synthesis, Characterization, and Anti-Inflammatory Activities of Methyl Salicylate Derivatives Bearing Piperazine Moiety.

PubMed

Li, Jingfen; Yin, Yong; Wang, Lisheng; Liang, Pengyun; Li, Menghua; Liu, Xu; Wu, Lichuan; Yang, Hua

2016-11-23

In this study, a new series of 16 methyl salicylate derivatives bearing a piperazine moiety were synthesized and characterized. The in vivo anti-inflammatory activities of target compounds were investigated against xylol-induced ear edema and carrageenan-induced paw edema in mice. The results showed that all synthesized compounds exhibited potent anti-inflammatory activities. Especially, the anti-inflammatory activities of compounds M15 and M16 were higher than that of aspirin and even equal to that of indomethacin at the same dose. In addition, the in vitro cytotoxicity activities and anti-inflammatory activities of four target compounds were performed in RAW264.7 macrophages, and compound M16 was found to significantly inhibit the release of lipopolysaccharide (LPS)-induced interleukin (IL)-6 and tumor necrosis factor (TNF)-α in a dose-dependent manner. In addition, compound M16 was found to attenuate LPS induced cyclooxygenase (COX)-2 up-regulation. The current preliminary study may provide information for the development of new and safe anti-inflammatory agents.

Characterizing and controlling the inflammatory network during influenza A virus infection

NASA Astrophysics Data System (ADS)

Jin, Suoqin; Li, Yuanyuan; Pan, Ruangang; Zou, Xiufen

2014-01-01

To gain insights into the pathogenesis of influenza A virus (IAV) infections, this study focused on characterizing the inflammatory network and identifying key proteins by combining high-throughput data and computational techniques. We constructed the cell-specific normal and inflammatory networks for H5N1 and H1N1 infections through integrating high-throughput data. We demonstrated that better discrimination between normal and inflammatory networks by network entropy than by other topological metrics. Moreover, we identified different dynamical interactions among TLR2, IL-1β, IL10 and NFκB between normal and inflammatory networks using optimization algorithm. In particular, good robustness and multistability of inflammatory sub-networks were discovered. Furthermore, we identified a complex, TNFSF10/HDAC4/HDAC5, which may play important roles in controlling inflammation, and demonstrated that changes in network entropy of this complex negatively correlated to those of three proteins: TNFα, NFκB and COX-2. These findings provide significant hypotheses for further exploring the molecular mechanisms of infectious diseases and developing control strategies.

A pilot study investigating the efficacy of botanical anti-inflammatory agents in an OTC eczema therapy.

PubMed

Draelos, Zoe Diana

2016-06-01

Eczema is a frequently encountered dermatologic condition characterized by inflammation resulting in erythema, scaling, induration, and lichenification. The objective of this research was to examine the roll of botanical anti-inflammatories in alleviating the signs and symptoms of mild-to-moderate eczema. A total of 25 subjects 18+ years of age with mild-to-moderate eczema were asked to leave all oral medications and cleansers unchanged substituting the botanical study moisturizer for all topical treatment three times daily for 2 weeks. Investigator, subject, and noninvasive assessments were obtained at baseline and week 2. There was a highly statistically significant (P < 0.001) improvement in investigator-assessed irritation, erythema, desquamation, roughness, dryness, lichenification, itching, and overall skin appearance after 2 weeks of botanical anti-inflammatory moisturizer use. Overall, a 79% reduction in itching was noted. Skin hydration as measured by corneometry increased 44% increase (P < 0.001). The study moisturizer containing the occlusive ingredients of dimethicone and shea butter oil; the humectant ingredients of glycerin, vitamin B, sodium PCA, and sodium hyaluronate; the barrier repair ingredients of ceramide 3, cholesterol, phytosphingosine, ceramide 6 II, and ceramide 1; and the botanical anti-inflammatories allantoin and bisabolol were helpful in reducing the signs and symptoms of mild-to-moderate eczema. © 2015 Wiley Periodicals, Inc.

Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent.

PubMed

Rupasinghe, H P Vasantha; Boehm, Mannfred M A; Sekhon-Loodu, Satvir; Parmar, Indu; Bors, Bob; Jamieson, Andrew R

2015-06-02

Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography-Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 10⁵/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor.

Anti-Inflammatory Activity of Haskap Cultivars is Polyphenols-Dependent

PubMed Central

Rupasinghe, H. P. Vasantha; Boehm, Mannfred M. A.; Sekhon-Loodu, Satvir; Parmar, Indu; Bors, Bob; Jamieson, Andrew R.

2015-01-01

Haskap (Lonicera caerulea L.) berries have long been used for their health promoting properties against chronic conditions. The current study investigated the effect of Canadian haskap berry extracts on pro-inflammatory cytokines using a human monocytic cell line THP-1 derived macrophages stimulated by lipopolysaccharide. Methanol extracts of haskap from different growing locations in Canada were prepared and characterized for their total phenolic profile using colorimetric assays and liquid chromatography—Mass spectrometry (UPLC-MS/MS). Human THP-1 monocytes were seeded in 24-well plates (5 × 105/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1 μg/mL) for 48 h to induce macrophage differentiation. After 48 h, the differentiated macrophages were washed with Hank’s buffer and treated with various concentrations of test compounds for 4 h, followed by the lipopolysaccharide (LPS)-stimulation (18 h). Borealis cultivar showed the highest phenolic content, flavonoid content and anthocyanin content (p < 0.05). A negative correlation existed between the polyphenol concentration of the extracts and pro-inflammatory cytokines: Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), prostaglandin (PGE2), and cyclooxygenase-2 (COX-2) enzyme. Borealis exhibited comparable anti-inflammatory effects to COX inhibitory drug, diclofenac. The results showed that haskap berry polyphenols has the potential to act as an effective inflammation inhibitor. PMID:26043379

AUTOINFLAMMATORY PUSTULAR NEUTROPHILIC DISEASES

PubMed Central

Naik, Haley B.; Cowen, Edward W.

2013-01-01

SYNOPSIS The inflammatory pustular dermatoses constitute a spectrum of non-infectious conditions ranging from localized involvement to generalized disease with associated acute systemic inflammation and multi-organ involvement. Despite the variability in extent and severity of cutaneous presentation, each of these diseases is characterized by non-infectious neutrophilic intra-epidermal microabscesses. Many share systemic findings including fever, elevated inflammatory markers, inflammatory bowel disease and/or osteoarticular involvement, suggesting potential common pathogenic links (Figure 1). The recent discoveries of several genes responsible for heritable pustular diseases have revealed a distinct link between pustular skin disease and regulation of innate immunity. These genetic advances have led to a deeper exploration of common pathways in pustular skin disease and offer the potential for a new era of biologic therapy which targets these shared pathways. This chapter provides a new categorization of inflammatory pustular dermatoses in the context of recent genetic and biologic insights. We will discuss recently-described monogenic diseases with pustular phenotypes, including deficiency of IL-1 receptor antagonist (DIRA), deficiency of the IL-36 receptor antagonist (DITRA), CARD14-associated pustular psoriasis (CAMPS), and pyogenic arthritis, pyoderma gangrenosum, acne (PAPA). We will then discuss how these new genetic advancements may inform how we view previously described pustular diseases, including pustular psoriasis and its clinical variants, with a focus on historical classification by clinical phenotype. PMID:23827244

Microbiota-specific Th17 cells: Yin and Yang in regulation of inflammatory bowel disease

PubMed Central

Wei, Wu; Feidi, Chen; Zhanju, Liu; Yingzi, Cong

2016-01-01

Multiple mechanisms are involved in regulation of host response to microbiota to maintain the intestinal homeostasis. Th17 cells are enriched in the intestinal lamina propria (LP) under steady conditions. Many studies have demonstrated that microbiota reactive Th17 cells in the intestines mediate the pathogenesis of inflammatory bowel diseases. However, clinical trials of anti-IL-17A or anti-IL-17RA antibodies in patients with Crohn’s Disease show no improvement or even exacerbation of disease. Accumulating data has also indicated that Th17 cells may provide a protective effect as well to the intestines from inflammatory insults under homeostasis regulation, even under inflammatory conditions. Thus both pro-inflammatory and anti-inflammatory functions of intestinal Th17 cells have emerged under various conditions. In this review article, we will summarize recent progresses of Th17 cells in regulation of intestinal homeostasis as well as in the pathogenesis of inflammatory bowel diseases. PMID:27057688

Leukocyte Inclusion within a Platelet Rich Plasma-Derived Fibrin Scaffold Stimulates a More Pro-Inflammatory Environment and Alters Fibrin Properties

PubMed Central

Anitua, Eduardo; Zalduendo, Mar; Troya, María; Padilla, Sabino; Orive, Gorka

2015-01-01

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions. PMID:25823008

[Fibrous tissue(s): a key for lesion characterization in digestive diseases].

PubMed

Régent, D; Laurent, V; Antunes, L; Debelle, L; Cannard, L; Leclerc, Jc; Beot, S

2002-02-01

Fibrosis is one of the hallmarks of inflammatory and repair processes in pathology. Various exogenous and endogenous stimuli, including tumor development, can induce inflammatory reactions. During the post-equilibrium phase after IV injection of non specific contrast media, CT and/or MR allow the study of these inflammatory answers to tumoral or infectious processes. Delayed enhancement of collagenic fibrous tissue during the late post-equilibrium phase is an essential complementary data in the characterization of many liver lesions: cirrhosis, cholangiocarcinoma, focal nodular hyperplasia, fibrous metastasis. but also for the differential diagnosis of pancreatic diseases (groove pancreatitis vs ductal adenocarcinoma) or of gastro-intestinal diseases (gastric adenocarcinoma vs lymphoma, mechanical complication vs inflammatory bouts of ileal Crohn's disease).

Inhibitory Effect of Natural Anti-Inflammatory Compounds on Cytokines Released by Chronic Venous Disease Patient-Derived Endothelial Cells

PubMed Central

Tisato, Veronica; Zauli, Giorgio; Rimondi, Erika; Gianesini, Sergio; Brunelli, Laura; Menegatti, Erica; Zamboni, Paolo; Secchiero, Paola

2013-01-01

Large vein endothelium plays important roles in clinical diseases such as chronic venous disease (CVD) and thrombosis; thus to characterize CVD vein endothelial cells (VEC) has a strategic role in identifying specific therapeutic targets. On these bases we evaluated the effect of the natural anti-inflammatory compounds α-Lipoic acid and Ginkgoselect phytosome on cytokines/chemokines released by CVD patient-derived VEC. For this purpose, we characterized the levels of a panel of cytokines/chemokines (n = 31) in CVD patients' plasma compared to healthy controls and their release by VEC purified from the same patients, in unstimulated and TNF-α stimulated conditions. Among the cytokines/chemokines released by VEC, which recapitulated the systemic profile (IL-8, TNF-α, GM-CSF, INF-α2, G-CSF, MIP-1β, VEGF, EGF, Eotaxin, MCP-1, CXCL10, PDGF, and RANTES), we identified those targeted by ex vivo treatment with α-Lipoic acid and/or Ginkgoselect phytosome (GM-CSF, G-CSF, CXCL10, PDGF, and RANTES). Finally, by investigating the intracellular pathways involved in promoting the VEC release of cytokines/chemokines, which are targeted by natural anti-inflammatory compounds, we documented that α-Lipoic acid significantly counteracted TNF-α-induced NF-κB and p38/MAPK activation while the effects of Ginkgo biloba appeared to be predominantly mediated by Akt. Our data provide new insights into the molecular mechanisms of CVD pathogenesis, highlighting new potential therapeutic targets. PMID:24489443

Effect of Dark Chocolate Extracts on Phorbol 12-Myristate 13-Acetate-Induced Oxidative Burst in Leukocytes Isolated by Normo-Weight and Overweight/Obese Subjects

PubMed Central

Ioannone, Francesca; Sacchetti, Giampiero; Serafini, Mauro

2017-01-01

Oxidative and inflammatory stress represents a major risk factor for cardiovascular disease (CVD) in overweight and obese subjects. Between the different plant foods, chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties. However, as we recently showed in epidemiological studies, meta-analyses, and human trials, dietary antioxidants resulted more effective in subjects characterized by an ongoing oxidative stress, than in healthy people. Aim of this work was to investigate the effect of different concentrations of chocolate phenolic extract (CPE) on in vitro free radical production, stimulated by phorbol 12-myristate 13-acetate (PMA), in leukocytes extracted from blood of normo-weight and overweight/obese subjects. Neutrophils from overweight/obese group had a significantly higher free radical production compared to the normo-weight group. In neutrophils, the lowest CPE concentration significantly reduced free radical production in overweight/obese group only, and higher CPE concentrations were effective in both groups. In monocytes, the CPE concentration that was significantly effective in reducing free radical production was lower in overweight/obese subjects than in normo-weight subjects. Chocolate polyphenol extracts inhibit oxidative burst in human neutrophils and monocytes with a higher efficiency in subjects characterized by an unphysiological oxidative/inflammatory stress, such as overweight and obese. Results of this study provide further evidence about a differential role of dietary antioxidant strictly related to the “stress” condition of the subjects. PMID:28649567

Effect of Dark Chocolate Extracts on Phorbol 12-Myristate 13-Acetate-Induced Oxidative Burst in Leukocytes Isolated by Normo-Weight and Overweight/Obese Subjects.

PubMed

Ioannone, Francesca; Sacchetti, Giampiero; Serafini, Mauro

2017-01-01

Oxidative and inflammatory stress represents a major risk factor for cardiovascular disease (CVD) in overweight and obese subjects. Between the different plant foods, chocolate has been shown to decrease CVD risk due to its antioxidant and anti-inflammatory properties. However, as we recently showed in epidemiological studies, meta-analyses, and human trials, dietary antioxidants resulted more effective in subjects characterized by an ongoing oxidative stress, than in healthy people. Aim of this work was to investigate the effect of different concentrations of chocolate phenolic extract (CPE) on in vitro free radical production, stimulated by phorbol 12-myristate 13-acetate (PMA), in leukocytes extracted from blood of normo-weight and overweight/obese subjects. Neutrophils from overweight/obese group had a significantly higher free radical production compared to the normo-weight group. In neutrophils, the lowest CPE concentration significantly reduced free radical production in overweight/obese group only, and higher CPE concentrations were effective in both groups. In monocytes, the CPE concentration that was significantly effective in reducing free radical production was lower in overweight/obese subjects than in normo-weight subjects. Chocolate polyphenol extracts inhibit oxidative burst in human neutrophils and monocytes with a higher efficiency in subjects characterized by an unphysiological oxidative/inflammatory stress, such as overweight and obese. Results of this study provide further evidence about a differential role of dietary antioxidant strictly related to the "stress" condition of the subjects.

Time-dependent LXR/RXR pathway modulation characterizes capillary remodeling in inflammatory corneal neovascularization.

PubMed

Mukwaya, Anthony; Lennikov, Anton; Xeroudaki, Maria; Mirabelli, Pierfrancesco; Lachota, Mieszko; Jensen, Lasse; Peebo, Beatrice; Lagali, Neil

2018-05-01

Inflammation in the normally immune-privileged cornea can initiate a pathologic angiogenic response causing vision-threatening corneal neovascularization. Inflammatory pathways, however, are numerous, complex and are activated in a time-dependent manner. Effective resolution of inflammation and associated angiogenesis in the cornea requires knowledge of these pathways and their time dependence, which has, to date, remained largely unexplored. Here, using a model of endogenous resolution of inflammation-induced corneal angiogenesis, we investigate the time dependence of inflammatory genes in effecting capillary regression and the return of corneal transparency. Endogenous capillary regression was characterized by a progressive thinning and remodeling of angiogenic capillaries and inflammatory cell retreat in vivo in the rat cornea. By whole-genome longitudinal microarray analysis, early suppression of VEGF ligand-receptor signaling and inflammatory pathways preceded an unexpected later-phase preferential activation of LXR/RXR, PPARα/RXRα and STAT3 canonical pathways, with a concurrent attenuation of LPS/IL-1 inhibition of RXR function and Wnt/β-catenin signaling pathways. Potent downstream inflammatory cytokines such as Cxcl5, IL-1β, IL-6 and Ccl2 were concomitantly downregulated during the remodeling phase. Upstream regulators of the inflammatory pathways included Socs3, Sparc and ApoE. A complex and coordinated time-dependent interplay between pro- and anti-inflammatory signaling pathways highlights a potential anti-inflammatory role of LXR/RXR, PPARα/RXRα and STAT3 signaling pathways in resolving inflammatory corneal angiogenesis.

Microbiota-specific Th17 Cells: Yin and Yang in Regulation of Inflammatory Bowel Disease.

PubMed

Wu, Wei; Chen, Feidi; Liu, Zhanju; Cong, Yingzi

2016-06-01

Multiple mechanisms are involved in regulation of host response to microbiota to maintain the intestinal homeostasis. Th17 cells are enriched in the intestinal lamina propria under steady conditions. Many studies have demonstrated that microbiota-reactive Th17 cells in the intestines mediate the pathogenesis of inflammatory bowel diseases. However, clinical trials of anti-interleukin-17A or anti-interleukin-17RA antibodies in patients with Crohn's Disease show no improvement or even exacerbation of disease. Accumulating data has also indicated that Th17 cells may provide a protective effect as well to the intestines from inflammatory insults under homeostasis regulation, even under inflammatory conditions. Thus both proinflammatory and anti-inflammatory functions of intestinal Th17 cells have emerged under various conditions. In this review article, we will summarize recent progresses of Th17 cells in regulation of intestinal homeostasis and in the pathogenesis of inflammatory bowel diseases.

Modulation of P2X7 Receptor during Inflammation in Multiple Sclerosis

PubMed Central

Amadio, Susanna; Parisi, Chiara; Piras, Eleonora; Fabbrizio, Paola; Apolloni, Savina; Montilli, Cinzia; Luchetti, Sabina; Ruggieri, Serena; Gasperini, Claudio; Laghi-Pasini, Franco; Battistini, Luca; Volonté, Cinzia

2017-01-01

Multiple sclerosis (MS) is characterized by macrophage accumulation and inflammatory infiltrates into the CNS contributing to demyelination. Because purinergic P2X7 receptor (P2X7R) is known to be abundantly expressed on cells of the hematopoietic lineage and of the nervous system, we further investigated its phenotypic expression in MS and experimental autoimmune encephalomyelitis conditions. By quantitative reverse transcription polymerase chain reaction and flow cytometry, we analyzed the P2X7R expression in human mononuclear cells of peripheral blood from stable and acute relapsing-remitting MS phases. Human monocytes were also challenged in vitro with pro-inflammatory stimuli such as the lipopolysaccharide, or the P2X7R preferential agonist 2′(3′)-O-(4 Benzoylbenzoyl)adenosine 5′-triphosphate, before evaluating P2X7R protein expression. Finally, by immunohistochemistry and immunofluorescence confocal analysis, we investigated the P2X7R expression in frontal cortex from secondary progressive MS cases. We demonstrated that P2X7R is present and inhibited on peripheral monocytes isolated from MS donors during the acute phase of the disease, moreover it is down-regulated in human monocytes after pro-inflammatory stimulation in vitro. P2X7R is instead up-regulated on astrocytes in the parenchyma of frontal cortex from secondary progressive MS patients, concomitantly with monocyte chemoattractant protein-1 chemokine, while totally absent from microglia/macrophages or oligodendrocytes, despite the occurrence of inflammatory conditions. Our results suggest that inhibition of P2X7R on monocytes and up-regulation in astrocytes might contribute to sustain inflammatory mechanisms in MS. By acquiring further knowledge about P2X7R dynamics and identifying P2X7R as a potential marker for the disease, we expect to gain insights into the molecular pathways of MS. PMID:29187851

TNFα Levels and Macrophages Expression Reflect an Inflammatory Potential of Trigeminal Ganglia in a Mouse Model of Familial Hemiplegic Migraine

PubMed Central

Franceschini, Alessia; Vilotti, Sandra; Ferrari, Michel D.; van den Maagdenberg, Arn M. J. M.; Nistri, Andrea; Fabbretti, Elsa

2013-01-01

Latent changes in trigeminal ganglion structure and function resembling inflammatory conditions may predispose to acute attacks of migraine pain. Here, we investigated whether, in trigeminal sensory ganglia, cytokines such as TNFα might contribute to a local inflammatory phenotype of a transgenic knock-in (KI) mouse model of familial hemiplegic migraine type-1 (FHM-1). To this end, macrophage occurrence and cytokine expression in trigeminal ganglia were compared between wild type (WT) and R192Q mutant CaV2.1 Ca2+ channel (R192Q KI) mice, a genetic model of FHM-1. Cellular and molecular characterization was performed using a combination of confocal immunohistochemistry and cytokine assays. With respect to WT, R192Q KI trigeminal ganglia were enriched in activated macrophages as suggested by their morphology and immunoreactivity to the markers Iba1, CD11b, and ED1. R192Q KI trigeminal ganglia constitutively expressed higher mRNA levels of IL1β, IL6, IL10 and TNFα cytokines and the MCP-1 chemokine. Consistent with the report that TNFα is a major factor to sensitize trigeminal ganglia, we observed that, following an inflammatory reaction evoked by LPS injection, TNFα expression and macrophage occurrence were significantly higher in R192Q KI ganglia with respect to WT ganglia. Our data suggest that, in KI trigeminal ganglia, the complex cellular and molecular environment could support a new tissue phenotype compatible with a neuroinflammatory profile. We propose that, in FHM patients, this condition might contribute to trigeminal pain pathophysiology through release of soluble mediators, including TNFα, that may modulate the crosstalk between sensory neurons and resident glia, underlying the process of neuronal sensitisation. PMID:23326332

Analysis of inflammatory cytokines in human blood, breath condensate, and urine using a multiplex immunoassay platform

EPA Science Inventory

A change in the expression of cytokines in human biological media indicates an inflammatory response to external stressors and reflects an early step along the adverse outcome pathway (AOP) for various health endpoints. To characterize and interpret this inflammatory response, m...

Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows.

PubMed

Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R; Olsen, Jesse R; Jeffress, Erin J; Moore, Dale A; Kastelic, John P

2013-11-09

Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05). Serum concentrations of adipokines, insulin, and IGF-1 had significant associations with BCS categories (low vs. high) and postpartum uterine inflammatory conditions. Perhaps loss of body condition mediated increases in anti- and pro-inflammatory cytokines, whereas increased pro- and anti-inflammatory cytokines concentrations mediated body condition loss and thereby prolonged persistence of uterine inflammation in dairy cows.

Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows

PubMed Central

2013-01-01

Background Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. Methods Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. Results Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05). Conclusions Serum concentrations of adipokines, insulin, and IGF-1 had significant associations with BCS categories (low vs. high) and postpartum uterine inflammatory conditions. Perhaps loss of body condition mediated increases in anti- and pro-inflammatory cytokines, whereas increased pro- and anti-inflammatory cytokines concentrations mediated body condition loss and thereby prolonged persistence of uterine inflammation in dairy cows. PMID:24209779

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: the use of natural compounds as modulatory agents.

PubMed

Giacomelli, Chiara; Natali, Letizia; Nisi, Marco; De Leo, Marinella; Daniele, Simona; Costa, Barbara; Graziani, Filippo; Gabriele, Mario; Braca, Alessandra; Trincavelli, M Letizia; Martini, Claudia

2018-05-11

Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs.

α7 Nicotinic Agonist AR-R17779 Protects Mice against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in a Spleen-Dependent Way.

PubMed

Grandi, Andrea; Zini, Irene; Flammini, Lisa; Cantoni, Anna M; Vivo, Valentina; Ballabeni, Vigilio; Barocelli, Elisabetta; Bertoni, Simona

2017-01-01

The existence of a cholinergic anti-inflammatory pathway negatively modulating the inflammatory and immune responses in various clinical conditions and experimental models has long been postulated. In particular, the protective involvement of the vagus nerve and of nicotinic Ach receptors (nAChRs) has been proposed in intestinal inflammation and repeatedly investigated in DSS- and TNBS-induced colitis. However, the role of α 7 nAChRs stimulation is still controversial and the potential contribution of α 4 β 2 nAChRs has never been explored in this experimental condition. Our aims were therefore to pharmacologically investigate the role played by both α 7 and α 4 β 2 nAChRs in the modulation of the local and systemic inflammatory responses activated in TNBS-induced colitis in mice and to assess the involvement of the spleen in nicotinic responses. To this end, TNBS-exposed mice were sub-acutely treated with various subcutaneous doses of highly selective agonists (AR-R17779 and TC-2403) and antagonists (methyllycaconitine and dihydro-β-erythroidine) of α 7 and α 4 β 2 nAChRs, respectively, or with sulfasalazine 50 mg/kg per os and clinical and inflammatory responses were evaluated by means of biochemical, histological and flow cytometry assays. α 4 β 2 ligands evoked weak and contradictory effects, while α 7 nAChR agonist AR-R17779 emerged as the most beneficial treatment, able to attenuate several local markers of colitis severity and to revert the rise in splenic T-cells and in colonic inflammatory cytokines levels induced by haptenization. After splenectomy, AR-R17779 lost its protective effects, demonstrating for the first time that, in TNBS-model of experimental colitis, the anti-inflammatory effect of exogenous α 7 nAChR stimulation is strictly spleen-dependent. Our findings showed that the selective α 7 nAChRs agonist AR-R17779 exerted beneficial effects in a model of intestinal inflammation characterized by activation of the adaptive immune system and that the spleen is essential to mediate this cholinergic protection.

[Intrathoracic-mediastinal myofibroblastic tumor. Report and experience of one case].

PubMed

Hernández-Ascencio, Julio Abraham; Rios-Cruz, Daniel; Grube-Pagola, Peter; Gómez-Calzada, Juan Gabriel

2014-01-01

Inflammatory pseudotumor is a little known and uncommon condition. The debate continues whether it represents an inflammatory lesion or is a true neoplasm. It is considered a reactive process usually characterized by irregular growth of inflammatory cells. It has been described at various sites, the most common being the lung. The aim of this report is to emphasize the difficulty in the initial diagnosis. We present the case of a 56-year-old male who reports an 8-month history of dry cough, dyspnea, fatigue, weakness and weight loss of 20 kg. We performed two biopsies, one positive for malignancy without response to medical treatment and the second reporting chronic granulomatous inflammation. The patient underwent sternotomy, revealing a tumor of 20 × 17 × 10 cm, weighing approximately 2 kg. The tumor was dependent on the anterior mediastinum surrounding large vessels, and venous brachiocephalic, pericardium and both pleuras with firm adhesions to the right lung. Pathological report was as follows: inflammatory myofibroblastic tumor with positive immunohistochemistry for CD20 and CD3. Postoperative course was satisfactory and 1 year after surgery there was no evidence of recurrence. Inflammatory pseudotumor is a benign neoplasm of unknown origin with a chronic course. It can simulate a malignant tumor, causing constitutional manifestations, airway obstruction, cardiac alterations or other symptoms according to their location. Diagnosis is based on radiological features and direct biopsy. Treatment of choice is complete resection of the tumor with a favorable long-term outcome.

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™

PubMed Central

Dykstra, Andrew B.; Sweeney, Matt D.; Leary, Julie A.

2013-01-01

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions. PMID:24970196

Structural Evidence for the Tetrameric Assembly of Chemokine CCL11 and the Glycosaminoglycan Arixtra™.

PubMed

Dykstra, Andrew B; Sweeney, Matt D; Leary, Julie A

2013-11-06

Understanding chemokine interactions with glycosaminoglycans (GAG) is critical as these interactions have been linked to a number of inflammatory medical conditions, such as arthritis and asthma. To better characterize in vivo protein function, comprehensive knowledge of multimeric species, formed by chemokines under native conditions, is necessary. Herein is the first report of a tetrameric assembly of the human chemokine CCL11, which was shown bound to the GAG Arixtra™. Isothermal titration calorimetry data indicated that CCL11 interacts with Arixtra, and ion mobility mass spectrometry (IM-MS) was used to identify ions corresponding to the CCL11 tetrameric species bound to Arixtra. Collisional cross sections (CCS) of the CCL11 tetramer-Arixtra noncovalent complex were compared to theoretical CCS values calculated using a preliminary structure of the complex deduced using X-ray crystallography. Experimental CCS values were in agreement with theoretical values, strengthening the IM-MS evidence for the formation of the noncovalent complex. Tandem mass spectrometry data of the complex indicated that the tetramer-GAG complex dissociates into a monomer and a trimer-GAG species, suggesting that two CC-like dimers are bridged by Arixtra. As development of chemokine inhibitors is of utmost importance to treatment of medical inflammatory conditions, these results provide vital insights into chemokine-GAG interactions.

Marine macromolecules cross-linked hydrogel scaffolds as physiochemically and biologically favorable entities for tissue engineering applications.

PubMed

Sumayya, A S; Muraleedhara Kurup, G

2017-06-01

Marine biopolymer composite materials provide a technological platform for launching biomedical applications. Biomaterials demand good biocompatibility without the possibility of inflammation or foreign body reactions. In this study, we prepared two biocomposite hydrogels namely; HAC (hydroxyapatite, alginate & chitosan) and HACF (hydroxyapatite, alginate, chitosan & fucoidan) followed by calcium chloride cross linking. The prepared scaffolds were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Porosity measurement, swelling, biodegradation, hemolysis, RBC aggregation, plasma protein adsorption and cytotoxicity studies were also done. The hydrogel scaffold HACF possessed a well-defined porous architecture, sufficient water holding capacity, better hemocompatibility and biodegradability. The biocompatibility was confirmed through in vitro cytotoxicity studies such as MTT assay, Neutral red uptake, DAPI staining, Trypan blue dye exclusion test and direct contact assay in L929 mouse fibroblast cells. In addition, immunomodulatory and anti-inflammatory properties of both of these scaffolds were revealed by the mRNA expressions of major inflammatory marker genes in cytotoxic condition such as TNF-α, IL-6 and NF-κB. The physiochemical characterization and biological responses of HACF hydrogel signifies its suitability for various tissue engineering applications.

Sunlight-driven photocatalytic degradation of non-steroidal anti-inflammatory drug based on TiO₂ quantum dots.

PubMed

Kaur, Amandeep; Umar, Ahmad; Kansal, Sushil Kumar

2015-12-01

This paper reports the facile synthesis, characterization and solar-light driven photocatalytic degradation of TiO2 quantum dots (QDs). The TiO2 QDs were synthesized by a facile ultrasonic-assisted hydrothermal process and characterized in terms of their structural, morphological, optical and photocatalytic properties. The detailed studies confirmed that the prepared QDs are well-crystalline, grown in high density and exhibiting good optical properties. Further, the prepared QDs were efficiently used as effective photocatalyst for the sun-light driven photocatalytic degradation of ketorolac tromethamine, a well-known non-steroidal anti-inflammatory drug (NSAID). To optimize the photocatalytic degradation conditions, various dose-dependent, pH-dependent, and initial drug-concentration dependent experiments were performed. The detailed solar-light driven photocatalytic experiments revealed that ∼99% photodegradation of ketorolac tromethamine drug solution (10 mg L(-1)) was observed with optimized amount of TiO2 QDs and pH (0.5 g L(-1) and 4.4, respectively) under solar-light irradiations. The observed results demonstrate that simply synthesized TiO2 QDs can efficiently be used for the solar-light driven photocatalytic degradation of harmful drugs and chemicals. Copyright © 2015 Elsevier Inc. All rights reserved.

Visible hyperspectral imaging evaluating the cutaneous response to ultraviolet radiation

NASA Astrophysics Data System (ADS)

Ilias, Michail A.; Häggblad, Erik; Anderson, Chris; Salerud, E. Göran

2007-02-01

In vivo diagnostics of skin diseases as well as understanding of the skin biology constitute a field demanding characterization of physiological and anatomical parameters. Biomedical optics has been successfully used, to qualitatively and quantitatively estimate the microcirculatory conditions of superficial skin. Capillaroscopy, laser Doppler techniques and spectroscopy, all elucidate different aspects of microcirculation, e.g. capillary anatomy and distribution, tissue perfusion and hemoglobin oxygenation. We demonstrate the use of a diffuse reflectance hyperspectral imaging system for spatial and temporal characterization of tissue oxygenation, important to skin viability. The system comprises: light source, liquid crystal tunable filter, camera objective, CCD camera, and the decomposition of the spectral signature into relative amounts of oxy- and deoxygenized hemoglobin as well as melanin in every pixel resulting in tissue chromophore images. To validate the system, we used a phototesting model, creating a graded inflammatory response of a known geometry, in order to evaluate the ability to register spatially resolved reflectance spectra. The obtained results demonstrate the possibility to describe the UV inflammatory response by calculating the change in tissue oxygen level, intimately connected to a tissue's metabolism. Preliminary results on the estimation of melanin content are also presented.

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions

PubMed Central

Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

2015-01-01

Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies. Significance The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. PMID:25979862

Oxygen Tension Regulates Human Mesenchymal Stem Cell Paracrine Functions.

PubMed

Paquet, Joseph; Deschepper, Mickael; Moya, Adrien; Logeart-Avramoglou, Delphine; Boisson-Vidal, Catherine; Petite, Hervé

2015-07-01

: Mesenchymal stem cells (MSCs) have captured the attention and research endeavors of the scientific world because of their differentiation potential. However, there is accumulating evidence suggesting that the beneficial effects of MSCs are predominantly due to the multitude of bioactive mediators secreted by these cells. Because the paracrine potential of MSCs is closely related to their microenvironment, the present study investigated and characterized select aspects of the human MSC (hMSC) secretome and assessed its in vitro and in vivo bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. In contrast to supernatant conditioned media (CM) obtained from hMSCs cultured at either 5% or 21% of O2, CM from hMSCs cultured under near anoxia exhibited significantly (p < .05) enhanced chemotactic and proangiogenic properties and a significant (p < .05) decrease in the inflammatory mediator content. An analysis of the hMSC secretome revealed a specific profile under near anoxia: hMSCs increase their paracrine expression of the angiogenic mediators vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, RANTES, and monocyte chemoattractant protein 1 but significantly decrease expression of several inflammatory/immunomodulatory mediators. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine and could contribute to improving the efficacy of such therapies. The present study investigated and characterized select aspects of the human mesenchymal stem cell (hMSC) secretome and assessed its in vitro and in vivo biological bioactivity as a function of oxygen tension, specifically near anoxia (0.1% O2) and hypoxia (5% O2), conditions that reflect the environment to which MSCs are exposed during MSC-based therapies in vivo. The present study provided the first evidence of a shift of the hMSC cytokine signature induced by oxygen tension, particularly near anoxia (0.1% O2). Conditioned media obtained from hMSCs cultured under near anoxia exhibited significantly enhanced chemotactic and proangiogenic properties and a significant decrease in the inflammatory mediator content. These findings provide new evidence that elucidates aspects of great importance for the use of MSCs in regenerative medicine, could contribute to improving the efficacy of such therapies, and most importantly highlighted the interest in using conditioned media in therapeutic modalities. ©AlphaMed Press.

Association of Dermatology Consultations With Patient Care Outcomes in Hospitalized Patients With Inflammatory Skin Diseases

PubMed Central

Milani-Nejad, Nima; Zhang, Myron

2017-01-01

Importance The value of inpatient dermatology consultations has traditionally been demonstrated with frequency in changes of diagnosis and management; however, the impact of dermatology consultations on metrics such as hospital length of stay and readmission rates remains unknown. Objective To determine the association of dermatology consultations with patient care in hospitalized patients using objective values. Design, Setting, and Participants We retrospectively queried the deidentified database of patients hospitalized between January 1, 2012, and December 31, 2014, at a single university medical center. A total of 413 patients with a primary inflammatory skin condition discharge diagnosis and 647 patients with primary inflammatory skin condition admission diagnosis were selected. Main Outcomes and Measures Hospital length of stay and 1-year readmission with inflammatory skin conditions. Results The 413 patients with a primary inflammatory skin condition discharge diagnosis were 61.0% female and had a mean (SD) age of 55.1 (16.4) years. The 647 patients with primary inflammatory skin condition admission diagnosis were 50.8% female and had a mean (SD) age of 57.8 (15.9) years. Multivariable modeling showed that dermatology consultations were associated with a reduction of 1-year inflammatory skin condition readmissions among patients who were discharged primarily with an inflammatory skin condition (readmission probability, 0.0025; 95% CI, 0.00020-0.030 with dermatology consult vs 0.026; 95% CI, 0.0065-0.10 without; odds ratio, 0.093; 95% CI, 0.010-0.840; P = .03). No other confounding variable was associated with reduction in readmissions. Multivariable modeling also showed that dermatology consultations were associated with a reduction in the adjusted hospital length of stay by 2.64 days (95% CI, 1.75-3.53 days; P < .001). Conclusions and Relevance Dermatology consultations were associated with improvements of outcomes among hospitalized patients. The expansion of the role of dermatology consultation services may improve patient care in a cost-effective manner. PMID:28296992

Association of Dermatology Consultations With Patient Care Outcomes in Hospitalized Patients With Inflammatory Skin Diseases.

PubMed

Milani-Nejad, Nima; Zhang, Myron; Kaffenberger, Benjamin H

2017-06-01

The value of inpatient dermatology consultations has traditionally been demonstrated with frequency in changes of diagnosis and management; however, the impact of dermatology consultations on metrics such as hospital length of stay and readmission rates remains unknown. To determine the association of dermatology consultations with patient care in hospitalized patients using objective values. We retrospectively queried the deidentified database of patients hospitalized between January 1, 2012, and December 31, 2014, at a single university medical center. A total of 413 patients with a primary inflammatory skin condition discharge diagnosis and 647 patients with primary inflammatory skin condition admission diagnosis were selected. Hospital length of stay and 1-year readmission with inflammatory skin conditions. The 413 patients with a primary inflammatory skin condition discharge diagnosis were 61.0% female and had a mean (SD) age of 55.1 (16.4) years. The 647 patients with primary inflammatory skin condition admission diagnosis were 50.8% female and had a mean (SD) age of 57.8 (15.9) years. Multivariable modeling showed that dermatology consultations were associated with a reduction of 1-year inflammatory skin condition readmissions among patients who were discharged primarily with an inflammatory skin condition (readmission probability, 0.0025; 95% CI, 0.00020-0.030 with dermatology consult vs 0.026; 95% CI, 0.0065-0.10 without; odds ratio, 0.093; 95% CI, 0.010-0.840; P = .03). No other confounding variable was associated with reduction in readmissions. Multivariable modeling also showed that dermatology consultations were associated with a reduction in the adjusted hospital length of stay by 2.64 days (95% CI, 1.75-3.53 days; P < .001). Dermatology consultations were associated with improvements of outcomes among hospitalized patients. The expansion of the role of dermatology consultation services may improve patient care in a cost-effective manner.

21 CFR 520.1720a - Phenylbutazone tablets and boluses.

Code of Federal Regulations, 2011 CFR

2011-04-01

... the relief of inflammatory conditions associated with the musculoskeletal system. (iii) Limitations... inflammatory conditions associated with the musculoskeletal system. (iii) Limitations. Do not use in horses...

The bacterial skin microbiome in psoriatic arthritis, an unexplored link in pathogenesis: challenges and opportunities offered by recent technological advances.

PubMed

Castelino, Madhura; Eyre, Stephen; Upton, Mathew; Ho, Pauline; Barton, Anne

2014-05-01

The resident microbial community, harboured by humans in sites such as the skin and gastrointestinal tract, is enormous, representing a candidate environmental factor affecting susceptibility to complex diseases, where both genetic and environmental risk factors are important. The potential of microorganisms to influence the human immune system is considerable, given their ubiquity. The impact of the host-gene-microbe interaction on the maintenance of health and the development of disease has not yet been assessed robustly in chronic inflammatory conditions. PsA represents a model inflammatory disease to explore the role of the microbiome because skin involvement and overlap with IBD implicates both the skin and gastrointestinal tract as sources of microbial triggers for PsA. In parallel with genetic studies, characterization of the host microbiota may benefit our understanding of the microbial contribution to disease pathogenesis-knowledge that may eventually inform the development of novel therapeutics.

Mulberry extract supplements ameliorate the inflammation-related hematological parameters in carrageenan-induced arthritic rats.

PubMed

Kim, Ae-Jung; Park, Soojin

2006-01-01

Mulberry fruit (Morus Lhou Koidz.), a rich source of the major anthocyanin, cyanidin 3-glucoside (C3G), has traditionally been used for the treatment of inflammatory conditions including rheumatic arthritis. In this study, we evaluated the efficacy of orally administrated methanolic mulberry fruit extract (ME) in carrageenan-induced arthritic rats, based on previously observed in vitro antioxidant and anti-inflammatory activities. A significant attenuation of hind paw inflammation characterized by fluid accumulation, uric acid production, and rheumatoid factors induced by carrageenan was observed following the intake of both ME (50 mg/kg of body weight) and C3G (10 mg/kg of body weight). Moreover, alterations in hematological parameters such as serum triglyceride, high-density lipoprotein-cholesterol, and atherogenic index following carrageenan administration were partially reversed by the administration of ME. It is concluded that dietary mulberry fruit extracts elicited protection against carrageenan-induced inflammation.

Malignant Melanoma of the Anus Found during Routine Colonoscopy in Ulcerative Colitis.

PubMed

Seo, Kwang Il; Moon, Won; Kim, Sung Eun; Park, Moo In; Park, Seun Ja

2017-06-25

Inflammatory bowel disease (IBD) is characterized by recurrent or chronic inflammation of the gastrointestinal tract, which results in increased risk of developing cancer. Anorectal malignant melanoma is often misdiagnosed as either hemorrhoids or benign anorectal conditions in inflammatory bowel disease. Therefore, the overall prognosis and survival of IBD are poor. To date, the best treatment strategy remains controversial. Only early diagnosis and complete excision yield survival benefit. Here, we report a 64-year-old woman with ulcerative colitis, who was found to have anal malignant melanoma on routine colonoscopy. The lesion was confined to the mucosa with no distant metastasis. She underwent complete trans-anal excision. There was no recurrence at the four-year follow-up. Physicians should be aware of increased risk of cancer development in IBD patients and remember the importance of meticulous inspection of the anal canal.

Pyoderma gangrenosum and ulcerative colitis in the tropics.

PubMed

Alese, Olatunji B; Irabor, David O

2008-01-01

Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.

Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor.

PubMed

Ribeiro, Alison; Ferraz-de-Paula, Viviane; Pinheiro, Milena L; Vitoretti, Luana B; Mariano-Souza, Domenica P; Quinteiro-Filho, Wanderley M; Akamine, Adriana T; Almeida, Vinícius I; Quevedo, João; Dal-Pizzol, Felipe; Hallak, Jaime E; Zuardi, Antônio W; Crippa, José A; Palermo-Neto, João

2012-03-05

Acute lung injury is an inflammatory condition for which treatment is mainly supportive because effective therapies have not been developed. Cannabidiol, a non-psychotropic cannabinoid component of marijuana (Cannabis sativa), has potent immunosuppressive and anti-inflammatory properties. Therefore, we investigated the possible anti-inflammatory effect of cannabidiol in a murine model of acute lung injury. Analysis of total inflammatory cells and differential in bronchoalveolar lavage fluid was used to characterize leukocyte migration into the lungs; myeloperoxidase activity of lung tissue and albumin concentration in the bronchoalveolar lavage fluid were analyzed by colorimetric assays; cytokine/chemokine production in the bronchoalveolar lavage fluid was also analyzed by Cytometric Bead Arrays and Enzyme-Linked Immunosorbent Assay (ELISA). A single dose of cannabidiol (20mg/kg) administered prior to the induction of LPS (lipopolysaccharide)-induced acute lung injury decreases leukocyte (specifically neutrophil) migration into the lungs, albumin concentration in the bronchoalveolar lavage fluid, myeloperoxidase activity in the lung tissue, and production of pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and MIP-2) 1, 2, and 4days after the induction of LPS-induced acute lung injury. Additionally, adenosine A(2A) receptor is involved in the anti-inflammatory effects of cannabidiol on LPS-induced acute lung injury because ZM241385 (4-(2-[7-Amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol) (a highly selective antagonist of adenosine A(2A) receptor) abrogated all of the anti-inflammatory effects of cannabidiol previously described. Thus, we show that cannabidiol has anti-inflammatory effects in a murine model of acute lung injury and that this effect is most likely associated with an increase in the extracellular adenosine offer and signaling through adenosine A(2A) receptor. Copyright © 2012 Elsevier B.V. All rights reserved.

Anti-inflammatory and immunomodulatory properties of Carica papaya.

PubMed

Pandey, Saurabh; Cabot, Peter J; Shaw, P Nicholas; Hewavitharana, Amitha K

2016-07-01

Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking.

Canonical Wnt signaling differently modulates osteogenic differentiation of mesenchymal stem cells derived from bone marrow and from periodontal ligament under inflammatory conditions.

PubMed

Liu, Wenjia; Konermann, Anna; Guo, Tao; Jäger, Andreas; Zhang, Liqiang; Jin, Yan

2014-03-01

Cellular plasticity and complex functional requirements of the periodontal ligament (PDL) assume a local stem cell (SC) niche to maintain tissue homeostasis and repair. Here, pathological alterations caused by inflammatory insults might impact the regenerative capacities of these cells. As bone homeostasis is fundamentally controlled by Wnt-mediated signals, it was the aim of this study to characterize the SC-like capacities of cells derived from PDL and to investigate their involvement in bone pathophysiology especially regarding the canonical Wnt pathway. PDLSCs were investigated for their SC characteristics via analysis of cell surface marker expression, colony forming unit efficiency, proliferation, osteogenic differentiation and adipogenic differentiation, and compared to bone marrow derived mesenchymal SCs (BMMSCs). To determine the impact of both inflammation and the canonical Wnt pathway on osteogenic differentiation, cells were challenged with TNF-α, maintained with or without Wnt3a or DKK-1 under osteogenic induction conditions and investigated for p-IκBα, p-NF-κB, p-Akt, β-catenin, p-GSK-3β, ALP and Runx2. PDLSCs exhibit weaker adipogenic and osteogenic differentiation capacities compared to BMMSCs. TNF-α inhibited osteogenic differentiation of PDLSCs more than BMMSCs mainly through regulating canonical Wnt pathway. Blocking the canonical Wnt pathway by DKK-1 reconstituted osteogenic differentiation of PDLSCs under inflammatory conditions, whereas activation by Wnt3a increased osteogenic differentiation of BMMSCs. Our results suggest a diverse regulation of the inhibitory effect of TNF-α in BMMSCs and PDLSCs via canonical Wnt pathway modulation. These findings provide novel insights on PDLSC SC-like capacities and their involvement in bone pathophysiology under the impact of the canonical Wnt pathway. Copyright © 2013 Elsevier B.V. All rights reserved.

Rifaximin - Chitosan Nanoparticles for Inflammatory Bowel Disease (IBD).

PubMed

Kumar, Jatinder; Newton, Amaldoss M J

2017-01-01

Inflammatory Bowel Disease (IBD) cannot be controlled easily and the recurrence is the most challenging issue for the physicians. There are various controlled and colon targeted drug delivery systems available for the treatment with limited success rate. Nanoparticles prepared by using the colon targeted polymers such as chitosan may improve the IBD due to their smaller size, unique physico chemical properties and targeting potential. The aim of this investigation was designed to formulate and develop a colon targeted polysaccharide nanoparticles of rifaximin (RFX) by using linear polysaccharide chitosan, for the improvement of rifaximin solubility, overall therapeutic efficacy and colon targeting. The research was focused on developing RFX nanoparticles for the treatment of Inflammatory Bowel Disease (IBD) by ionic gelation method. Nanoparticles were subjected to various characterization techniques such as XRD, FTIR and mean particle size (MPS) by Master Sizer and Zeta Sizer. Transmission Electron Microscopy (TEM), drug entrapment efficiency and zeta potential are also determined for the developed formulations. The efficiency of drug release from prepared formulation was studied in vitro by using a dialysis bag diffusion technique in the buffer condition mimicking stomach, intestine and colonic pH conditions. The prepared nanoparticles demonstrated the size in the nano range. The drug release profile was controlled in the upper GI tract and the maximum amount of drug was released in the colonic conditions. The prepared nanoparticles significantly improved the solubility of rifaximin. The zeta potential of the best chitosan preparation was found to be 37.79, which confirms the stability of prepared nanosuspension. Nanoparticles with small particle size found to have high encapsulation efficiency and relatively high loading capacity and predetermined in vitro release profile. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

PubMed

Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

2017-09-01

Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

Human periodontal ligament stem cells secretome from multiple sclerosis patients suppresses NALP3 inflammasome activation in experimental autoimmune encephalomyelitis

PubMed Central

Soundara Rajan, Thangavelu; Giacoppo, Sabrina; Diomede, Francesca; Bramanti, Placido; Trubiani, Oriana; Mazzon, Emanuela

2017-01-01

Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called “secretome,” in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell–derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction. PMID:28764573

Interleukin-6 Responses to Water Immersion Therapy After Acute Exercise Heat Stress: A Pilot Investigation

PubMed Central

Lee, Elaine C.; Watson, Greig; Casa, Douglas; Armstrong, Lawrence E.; Kraemer, William; Vingren, Jakob L.; Spiering, Barry A.; Maresh, Carl M.

2012-01-01

Context Cold-water immersion is the criterion standard for treatment of exertional heat illness. Cryotherapy and water immersion also have been explored as ergogenic or recovery aids. The kinetics of inflammatory markers, such as interleukin-6 (IL-6), during cold-water immersion have not been characterized. Objective To characterize serum IL-6 responses to water immersion at 2 temperatures and, therefore, to initiate further research into the multidimensional benefits of immersion and the evidence-based selection of specific, optimal immersion conditions by athletic trainers. Design Controlled laboratory study. Setting Human performance laboratory Patients or Other Participants Eight college-aged men (age = 22 ± 3 years, height = 1.76 ± 0.08 m, mass = 77.14 ± 9.77 kg, body fat = 10% ± 3%, and maximal oxygen consumption = 50.48 ± 4.75 mL·kg−1·min−1). Main Outcome Measures Participants were assigned randomly to receive either cold (11.70°C ± 2.02°C, n = 4) or warm (23.50°C ± 1.00°C, n = 4) water-bath conditions after exercise in the heat (temperature = 37°C, relative humidity = 52%) for 90 minutes or until volitional cessation. Results Whole-body cooling rates were greater in the cold water-bath condition for the first 6 minutes of water immersion, but during the 90-minute, postexercise recovery, participants in the warm and cold water-bath conditions experienced similar overall whole-body cooling. Heart rate responses were similar for both groups. Participants in the cold water-bath condition experienced an overall slight increase (30.54% ± 77.37%) in IL-6 concentration, and participants in the warm water-bath condition experienced an overall decrease (−69.76% ± 15.23%). Conclusions We have provided seed evidence that cold-water immersion is related to subtle IL-6 increases from postexercise values and that warmer water-bath temperatures might dampen this increase. Further research will elucidate any anti-inflammatory benefit associated with water-immersion treatment and possible multidimensional uses of cooling therapies. PMID:23182014

[Neonatal suppurative parotitis in a six-day-old, mature boy].

PubMed

Sass, Lærke Louise Reeberg; Nielsen, Allan Bybeck

2016-11-28

Neonatal suppurative parotitis is a rare condition with approximately 50 cases reported in the literature in English since 1970. It is characterized by parotid swelling along with other local inflammatory sign, and some neonates present with fever and irritability. Pus secretion from the ipsilateral parotid duct is pathognomonic. The most common pathogen is Staphylococcus aureus, but other microorganisms are reported. We describe a case of a six-day-old, mature boy, previously healthy, who presented with fever, tender swelling of the right parotid and pus secretion from the parotid duct.

Nutraceutical, Anti-Inflammatory, and Immune Modulatory Effects of β-Glucan Isolated from Yeast

PubMed Central

Bacha, Umar; Iqbal, Sanaullah; Anjum, Aftab Ahmad

2017-01-01

β-Glucan is a dietary fibre, found in many natural sources, and controls chronic metabolic diseases effectively. However, β-glucan from the yeast has rarely been investigated. Objectively, conditions were optimized to isolate β-glucan from the yeast (max. 66% yield); those optimized conditions included 1.0 M NaOH, pH 7.0, and 90°C. The purity and identity of the isolated β-glucan were characterized through FT-IR, SEM, DSC, and physicofunctional properties. The obtained results from DSC revealed highly stable β-glucan (m.p., 125°C) with antioxidant activity (TAC value 0.240 ± 0.0021 µg/mg, H2O2 scavenging 38%), which has promising bile acid binding 40.463% and glucose control (in vitro). In line with these results, we evaluated the in vivo anti-inflammatory potential, that is, myeloperoxidase activity and reduction in MDA and NO; protective effect on proteins and keeping viscosity within normal range exhibited improvement. Also, the in vivo cholesterol binding and reduction in the skin thickness by β-glucan were highly encouraging. Finally, our results confirmed that yeast β-glucan is effective against some of the inflammatory and oxidative stress markers studied in this investigation. In general, the effect of 4%  β-glucan was more noticeable versus 2%  β-glucan. Therefore, our results support the utilization of β-glucan as a novel, economically cheap, and functional food ingredient. PMID:28913359

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond.

PubMed

Michopoulos, Vasiliki; Powers, Abigail; Gillespie, Charles F; Ressler, Kerry J; Jovanovic, Tanja

2017-01-01

The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions.

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

PubMed Central

Michopoulos, Vasiliki; Powers, Abigail; Gillespie, Charles F; Ressler, Kerry J; Jovanovic, Tanja

2017-01-01

The study of inflammation in fear- and anxiety-based disorders has gained interest as growing literature indicates that pro-inflammatory markers can directly modulate affective behavior. Indeed, heightened concentrations of inflammatory signals, including cytokines and C-reactive protein, have been described in posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias (agoraphobia, social phobia, etc.). However, not all reports indicate a positive association between inflammation and fear- and anxiety-based symptoms, suggesting that other factors are important in future assessments of inflammation's role in the maintenance of these disorders (ie, sex, co-morbid conditions, types of trauma exposure, and behavioral sources of inflammation). The most parsimonious explanation of increased inflammation in PTSD, GAD, PD, and phobias is via the activation of the stress response and central and peripheral immune cells to release cytokines. Dysregulation of the stress axis in the face of increased sympathetic tone and decreased parasympathetic activity characteristic of anxiety disorders could further augment inflammation and contribute to increased symptoms by having direct effects on brain regions critical for the regulation of fear and anxiety (such as the prefrontal cortex, insula, amygdala, and hippocampus). Taken together, the available data suggest that targeting inflammation may serve as a potential therapeutic target for treating these fear- and anxiety-based disorders in the future. However, the field must continue to characterize the specific role pro-inflammatory signaling in the maintenance of these unique psychiatric conditions. PMID:27510423

Maladaptive immune and inflammatory pathways lead to cardiovascular insulin resistance.

PubMed

Aroor, Annayya R; McKarns, Susan; Demarco, Vincent G; Jia, Guanghong; Sowers, James R

2013-11-01

Insulin resistance is a hallmark of obesity, the cardiorenal metabolic syndrome and type 2 diabetes mellitus (T2DM). The progression of insulin resistance increases the risk for cardiovascular disease (CVD). The significance of insulin resistance is underscored by the alarming rise in the prevalence of obesity and its associated comorbidities in the Unites States and worldwide over the last 40-50 years. The incidence of obesity is also on the rise in adolescents. Furthermore, premenopausal women have lower CVD risk compared to men, but this protection is lost in the setting of obesity and insulin resistance. Although systemic and cardiovascular insulin resistance is associated with impaired insulin metabolic signaling and cardiovascular dysfunction, the mechanisms underlying insulin resistance and cardiovascular dysfunction remain poorly understood. Recent studies show that insulin resistance in obesity and diabetes is linked to a metabolic inflammatory response, a state of systemic and tissue specific chronic low grade inflammation. Evidence is also emerging that there is polarization of macrophages and lymphocytes towards a pro-inflammatory phenotype that contributes to progression of insulin resistance in obesity, cardiorenal metabolic syndrome and diabetes. In this review, we provide new insights into factors, such as, the renin-angiotensin-aldosterone system, sympathetic activation and incretin modulators (e.g., DPP-4) and immune responses that mediate this inflammatory state in obesity and other conditions characterized by insulin resistance. © 2013.

Yeast (Saccharomyces cerevisiae) Polarizes Both M-CSF- and GM-CSF-Differentiated Macrophages Toward an M1-Like Phenotype.

PubMed

Seif, Michelle; Philippi, Anja; Breinig, Frank; Kiemer, Alexandra K; Hoppstädter, Jessica

2016-10-01

Macrophages are a heterogeneous and plastic cell population with two main phenotypes: pro-inflammatory classically activated macrophages (M1) and anti-inflammatory alternatively activated macrophages (M2). Saccharomyces cerevisiae is a promising vehicle for the delivery of vaccines. It is well established that S. cerevisiae is taken up by professional phagocytic cells. However, the response of human macrophages to S. cerevisiae is ill-defined. In this study, we characterized the interaction between S. cerevisiae and M1- or M2-like macrophages. M1-like macrophages had a higher yeast uptake capacity than M2-like macrophages, but both cell types internalized opsonized yeast to the same extent. The M1 surface markers HLAII and CD86 were upregulated after yeast uptake in M1- and M2-like macrophages. Moreover, mRNA expression levels of pro-inflammatory cytokines, such as TNF-α, IL-12, and IL-6, increased, whereas the expression of anti-inflammatory mediators did not change. These results demonstrate that S. cerevisiae can target both M1 and M2 macrophages, paralleled by skewing toward an M1 phenotype. Thus, the use of yeast-based delivery systems might be a promising approach for the treatment of pathologic conditions that would benefit from the presence of M1-polarized macrophages, such as cancer.

Study of osteoarthritis treatment with anti-inflammatory drugs: cyclooxygenase-2 inhibitor and steroids.

PubMed

Cho, Hongsik; Walker, Andrew; Williams, Jeb; Hasty, Karen A

2015-01-01

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-α was incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxib in vivo was investigated using a posttraumatic OA (PTOA) mouse model. In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 production in vitro and that celecoxib may demonstrate beneficial effects on anabolic metabolism in vivo.

Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease.

PubMed

Robb, Lorraine; Boyle, Kristy; Rakar, Steven; Hartley, Lynne; Lochland, Janelle; Roberts, Andrew W; Alexander, Warren S; Metcalf, Donald

2005-11-08

The suppressor of cytokine-signaling (SOCS) proteins act as negative-feedback inhibitors of cytokine and growth-factor-induced signal transduction. In vivo studies have implicated SOCS3 as a negative regulator of signaling downstream of gp130, the receptor subunit shared by IL-6-like cytokines. Mice lacking SOCS3 die at midgestation because of placental failure, and SOCS3 ablation in a cell-type-specific manner results in changes in the functional outcome of gp130 signaling in response to IL-6. In this study, we show that genetic reduction of leukemia-inhibitory factor (LIF) production by embryo-derived tissues is sufficient to prevent the placental defect. This establishes LIF signaling as a major physiological regulator of trophoblast differentiation in vivo. Mice deficient in both SOCS3 and LIF are born in predicted numbers and appear normal at birth but exhibit failure to thrive and high neonatal mortality. Adult SOCS3-null mice on a LIF-null background succumb to a spontaneous fatal inflammatory disease characterized by neutrophilia and inflammatory-cell tissue infiltrates. The disease spectrum mimics that seen in mice with a conditional deletion of SOCS3 in hematopoietic and endothelial cells, extending the evidence for a major role for SOCS3 in the homeostatic regulation of the inflammatory response and indicates that LIF is not required for this process.

Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease

PubMed Central

Robb, Lorraine; Boyle, Kristy; Rakar, Steven; Hartley, Lynne; Lochland, Janelle; Roberts, Andrew W.; Alexander, Warren S.; Metcalf, Donald

2005-01-01

The suppressor of cytokine-signaling (SOCS) proteins act as negative-feedback inhibitors of cytokine and growth-factor-induced signal transduction. In vivo studies have implicated SOCS3 as a negative regulator of signaling downstream of gp130, the receptor subunit shared by IL-6-like cytokines. Mice lacking SOCS3 die at midgestation because of placental failure, and SOCS3 ablation in a cell-type-specific manner results in changes in the functional outcome of gp130 signaling in response to IL-6. In this study, we show that genetic reduction of leukemia-inhibitory factor (LIF) production by embryo-derived tissues is sufficient to prevent the placental defect. This establishes LIF signaling as a major physiological regulator of trophoblast differentiation in vivo. Mice deficient in both SOCS3 and LIF are born in predicted numbers and appear normal at birth but exhibit failure to thrive and high neonatal mortality. Adult SOCS3-null mice on a LIF-null background succumb to a spontaneous fatal inflammatory disease characterized by neutrophilia and inflammatory-cell tissue infiltrates. The disease spectrum mimics that seen in mice with a conditional deletion of SOCS3 in hematopoietic and endothelial cells, extending the evidence for a major role for SOCS3 in the homeostatic regulation of the inflammatory response and indicates that LIF is not required for this process. PMID:16258063

[Recent advances in Saccharomyces boulardii research].

PubMed

Im, E; Pothoulakis, C

2010-09-01

This review summarizes the probiotic mechanisms of action of Saccharomyces boulardii (S. boulardii) against inflammatory and non-inflammatory diarrheal conditions. S. boulardii is distributed in lyophilized form in many countries and used for the prevention of diarrhea in children and adults, including Clostridium difficile (C. difficile) associated infection. The main mechanisms of action of S. boulardii include inhibition of activities of bacterial pathogenic products, trophic effects on the intestinal mucosa, as well as modification of host signaling pathways involved in inflammatory and non-inflammatory intestinal diseases. S. boulardii inhibits production of pro-inflammatory cytokines by inhibiting main regulators of inflammation, including nuclear factor κB (NF-κB), and mitogen-activated protein kinases (MAP kinases), ERK1/2 and p38, but stimulates production of anti-inflammatory molecules such as peroxisome proliferator-activated receptor-gamma (PPAR-γ). Moreover, S. boulardii suppresses bacterial infection by inhibiting adhesion and/or overgrowth of bacteria, produces a serine protease that cleaves C. difficile toxin A, and stimulates antibody production against this toxin. Furthermore, S. boulardii may interfere with pathogenesis of Inflammatory Bowel Disease (IBD) by acting on T cells and acts in diarrheal conditions by improving the fecal biostructure in patients with diarrhea. These diverse mechanisms exerted by S. boulardii provide molecular clues for its effectiveness in diarrheal diseases and intestinal inflammatory conditions with an inflammatory component. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

PubMed

Cattaruzza, Fiore; Johnson, Cali; Leggit, Alan; Grady, Eileen; Schenk, A Katrin; Cevikbas, Ferda; Cedron, Wendy; Bondada, Sandhya; Kirkwood, Rebekah; Malone, Brian; Steinhoff, Martin; Bunnett, Nigel; Kirkwood, Kimberly S

2013-06-01

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

Cardiovascular Involvement in Autoimmune Diseases

PubMed Central

Amaya-Amaya, Jenny

2014-01-01

Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

Exploring Inflammatory Disease Drug Effects on Neutrophil Function

PubMed Central

Wu, Xiaojie; Kim, Donghyuk; Young, Ashlyn T.; Haynes, Christy L.

2014-01-01

Neutrophils are critical inflammatory cells; thus, it is important to characterize the effects of drugs on neutrophil function in the context of inflammatory diseases. Herein, chemically guided neutrophil migration, known as chemotaxis, is studied in the context of drug treatment at the single cell level using a microfluidic platform, complemented by cell viability assays and calcium imaging. Three representative drugs known to inhibit surface receptor expression, signaling enzyme activity, and the elevation of intracellular Ca2+ levels, each playing a significant role in neutrophil chemotactic pathways, are used to examine the in vitro drug effects on cellular behaviors. The microfluidic device establishes a stable concentration gradient of chemokines across a cell culture chamber so that neutrophil migration can be monitored under various drug-exposure conditions. Different time- and concentration-dependent regulatory effects were observed by comparing the motility, polarization, and effectiveness of neutrophil chemotaxis in response to the three drugs. Viability assays revealed distinct drug capabilities in reducing neutrophil viability while calcium imaging clarified the role of Ca2+ in the neutrophil chemotactic pathway. This study provides mechanistic insight into the drug effects on neutrophil function, facilitating comparison of current and potential pharmaceutical approaches. PMID:24946254

Optical biopsy of pre-malignant or degenerative lesions: the role of the inflammatory process

NASA Astrophysics Data System (ADS)

da Silva Martinho, Herculano

2011-03-01

Recent technological advances in fiber optics, light sources, detectors, and molecular biology have stimulated unprecedented development of optical methods to detect pathological changes in tissues. These methods, collectively termed "optical biopsy," are nondestructive in situ and real-time assays. Optical biopsy techniques as fluorescence spectroscopy, polarized light scattering spectroscopy, optical coherence tomography, confocal reflectance microscopy, and Raman spectroscopy had been extensively used to characterize several pathological tissues. In special, Raman spectroscopy technique had been able to probe several biochemical alterations due to pathology development as change in the DNA, glycogen, phospholipid, non-collagenous proteins. All studies claimed that the optical biopsy methods were able to discriminate normal and malignant tissues. However, few studies had been devoted to the discrimination of very common subtle or early pathological states as inflammatory process, which are always present on, e.g., cancer lesion border. In this work we present a systematic comparison of optical biopsy data on several kinds of lesions were inflammatory infiltrates play the role (breast, cervical, and oral lesion). It will be discussed the essential conditions for the optimization of discrimination among normal and alterated states based on statistical analysis.

Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue.

PubMed

Fusaru, Ana Marina; Stănciulescu, Camelia Elena; Surlin, V; Taisescu, C; Bold, Adriana; Pop, O T; Baniţă, Ileana Monica; Crăiţoiu, Stefania; Pisoschi, Cătălina Gabriela

2012-01-01

White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.

An in vitro examination of the antioxidant, cytoprotective and anti-inflammatory properties of chrysin-loaded nanofibrous mats for potential wound healing applications.

PubMed

Deldar, Yaghoub; Pilehvar-Soltanahmadi, Younes; Dadashpour, Mehdi; Montazer Saheb, Soheila; Rahmati-Yamchi, Mohammad; Zarghami, Nosratollah

2018-06-01

Chrysin (Chr) is a naturally occurring flavone with a wide spectrum of biological functions including anti-cancer, anti-inflammatory and anti-oxidant properties. Due to the low bioavailability and in vivo stability of Chr at therapeutic levels for wound-healing applications, Chr-loaded PCL/PEG nanofibrous mats were successfully fabricated by optimizing the electrospinning parameters and characterized using FE-SEM and FTIR. Results of MTT showed that Human foreskin fibroblast cells (HFF-1) have more than 80% viability on Chr-loaded nanofibers. The antioxidant activity of Chr-loaded PCL/PEG electrospun nanofibers was demonstrated applying an ORAC assay and by the capability of the nanofibers to maintain the viability of HFF-1 cells on the mats under an oxidative stress condition. The Chr-blended PCL/PEG nanofibrous mats also reduced overexpression of IL-6, IL-1β, TNF-α and excessive production of nitric oxide (NO) in J774A1 following stimulation by lipopolysaccharide (LPS). These results suggest that the proposed natural substance based nanofibrous mats can accelerate wound healing process with cell proliferation, antioxidative and anti-inflammatory activities.

Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions

PubMed Central

Kolářová, Hana; Ambrůzová, Barbora; Švihálková Šindlerová, Lenka; Klinke, Anna; Kubala, Lukáš

2014-01-01

The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed. PMID:24803742

Middle Ear Fluid Cytokine and Inflammatory Cell Kinetics in the Chinchilla Otitis Media Model

PubMed Central

Sato, Katsuro; Liebeler, Carol L.; Quartey, Moses K.; Le, Chap T.; Giebink, G. Scott

1999-01-01

Streptococcus pneumoniae is the most frequent microbe causing middle ear infection. The pathophysiology of pneumococcal otitis media has been characterized by measurement of local inflammatory mediators such as inflammatory cells, lysozyme, oxidative metabolic products, and inflammatory cytokines. The role of cytokines in bacterial infection has been elucidated with animal models, and interleukin (IL)-1β, IL-6, and IL-8 and tumor necrosis factor alpha (TNF-α) are recognized as being important local mediators in acute inflammation. We characterized middle ear inflammatory responses in the chinchilla otitis media model after injecting a very small number of viable pneumococci into the middle ear, similar to the natural course of infection. Middle ear fluid (MEF) concentrations of IL-1β, IL-6, IL-8, and TNF-α were measured by using anti-human cytokine enzyme-linked immunosorbent assay reagents. IL-1β showed the earliest peak, at 6 h after inoculation, whereas IL-6, IL-8, and TNF-α concentrations were increasing 72 h after pneumococcal inoculation. IL-6, IL-8, and TNF-α but not IL-1β concentrations correlated significantly with total inflammatory cell numbers in MEF, and all four cytokines correlated significantly with MEF neutrophil concentration. Several intercytokine correlations were significant. Cytokines, therefore, participate in the early middle ear inflammatory response to S. pneumoniae. PMID:10085040

Current drug therapies for rosacea: a chronic vascular and inflammatory skin disease.

PubMed

Feldman, Steven R; Huang, William W; Huynh, Tu T

2014-06-01

Rosacea is a chronic skin disorder that presents with abnormal vascular and inflammatory conditions. Clinical manifestations include flushing, facial erythema, inflammatory papules and pustules, telangiectasias, edema, and watery or irritated eyes. To discuss the evolving pathophysiology of rosacea, factors involved in promoting the chronic vascular and inflammatory abnormalities seen in rosacea, and the available drug therapies for the condition. Chronic inflammation and vascular changes are believed to be underlying factors in the pathophysiology of rosacea. Aberrant cathelicidin expression, elevated kallikrein 5 (KLK5) proteolytic activity, and altered toll-like receptor 2 (TLR2) expression have been reported in rosacea skin leading to the production of proinflammatory cytokines. Until recently, drug therapies only targeted the inflammatory lesions (papules and pustules) and transient erythema associated with these inflammatory lesions of rosacea. Brimonidine tartrate gel 0.5% was recently approved for the treatment of persistent (nontransient) facial erythema of rosacea, acting primarily on the cutaneous vascular component of the disease. Rosacea is a chronic vascular and inflammatory skin disease. Understanding the role of factors that trigger the onset of rosacea symptoms and exacerbate the condition is crucial in treating this skin disease.

Endometriosis: translation of molecular insights to management.

PubMed

Langan, K L; Farrell, M E; Keyser, E A; Salyer, B A; Burney, R O

2014-09-01

Endometriosis is a debilitating gynecologic disorder causing pelvic pain and infertility and characterized by the implantation of endometrial tissue to extrauterine locations. Though aspects of the condition remain enigmatic, the molecular pathophysiology of endometriosis appears to be clarifying. Estrogen dependence of the disease is a sentinel endocrine feature and reduction of estrogen bioavailability is the therapeutic principle upon which traditional treatment and prevention approaches have been based. Endometriosis is a chronic inflammatory condition associated with lesional neoangiogenesis and attenuated progesterone action at the level of the endometrium. The elucidation of the molecular pathways mediating these observations has revealed new targets for directed medical and surgical treatment. This paper will review current approaches to the management of endometriosis in the context of the molecular pathophysiology.

Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators.

PubMed

Wang, Xiaoshuang; Yang, Liu; Yang, Li; Xing, Faping; Yang, Hua; Qin, Liyue; Lan, Yunyi; Wu, Hui; Zhang, Beibei; Shi, Hailian; Lu, Cheng; Huang, Fei; Wu, Xiaojun; Wang, Zhengtao

2017-12-01

Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo. GP IX significantly reduced the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) at either protein or mRNA level in glial cell line C6 cells stimulated by lipopolysaccharide (LPS)/TNF-α combination. It also alleviated the astrogliosis and decreased the production of inflammatory mediators in brain cortex of LPS-treated mice. Further study disclosed that GP IX inhibited nuclear translocation of nuclear factor kappa B (NFκB) and reduced its transcriptional activity. Meanwhile, GP IX significantly attenuated the phosphorylation of NFκB, inhibitor of kappa B (IκB), Akt, and p38 mitogen-activated protein kinase (MAPK) under inflammatory conditions both in vitro and in vivo. These findings indicated that GP IX might suppress reactive astrogliosis by suppressing Akt/p38 MAPK/NFκB signaling pathways. And GP IX might be a promising drug candidate or prodrug for the therapy of neuroinflammatory disorders characterized with reactive astrogliosis.

The Salivary Microbiome in Polycystic Ovary Syndrome (PCOS) and Its Association with Disease-Related Parameters: A Pilot Study.

PubMed

Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Pieber, Thomas R; Gorkiewicz, Gregor; Obermayer-Pietsch, Barbara

2016-01-01

Polycystic ovary syndrome (PCOS) is a common female endocrine condition of unclear etiology characterized by hyperandrogenism, oligo/amenorrhoea, and polycystic ovarian morphology. PCOS is often complicated by infertility, overweight/obesity, insulin resistance, and low-grade inflammation. The gut microbiome is known to contribute to several of these conditions. Recently, an association between stool and saliva microbiome community profiles was shown, making saliva a possible convenient, non-invasive sample type for detecting gut microbiome changes in systemic disease. In this study, we describe the saliva microbiome of PCOS patients and the association of microbiome features with PCOS-related parameters. 16S rRNA gene amplicon sequencing was performed on saliva samples from 24 PCOS patients and 20 healthy controls. Data processing and microbiome analyses were conducted in mothur and QIIME. All study subjects were characterized regarding reproductive, metabolic, and inflammatory parameters. PCOS patients showed a decrease in bacteria from the phylum Actinobacteria and a borderline significant shift in bacterial community composition in unweighted UniFrac analysis. No differences between patients and controls were found in alpha diversity, weighted UniFrac analysis, or on other taxonomic levels. We found no association of saliva alpha diversity, beta diversity, or taxonomic composition with serum testosterone, oligo/amenorrhoea, overweight, insulin resistance, inflammatory markers, age, or diet. In this pilot study, patients with PCOS showed a reduced salivary relative abundance of Actinobacteria. Reproductive and metabolic components of the syndrome were not associated with saliva microbiome parameters, indicating that the majority of between-subject variation in saliva microbiome profiles remains to be explained.

Epstein-Barr virus viral load and serology in childhood non-Hodgkin's lymphoma and chronic inflammatory conditions in Uganda: implications for disease risk and characteristics.

PubMed

Orem, Jackson; Sandin, Sven; Mbidde, Edward; Mangen, Fred Wabwire; Middeldorp, Jaap; Weiderpass, Elisabete

2014-10-01

Epstein-Barr virus (EBV) has been linked to malignancies and chronic inflammatory conditions. In this study, EBV detection was compared in children with non-Hodgkin's lymphoma and children with chronic inflammatory conditions, using samples and data from a case-control study carried out at the Mulago National Referral Hospital between 2004 and 2008. EBV viral load was measured in saliva, whole blood and white blood cells by real-time PCR. Serological values for IgG-VCA, EBNA1, and EAd-IgG were compared in non-Hodgkin's lymphoma and chronic inflammatory conditions; and in Burkitt's lymphoma and other subtypes of non-Hodgkin's lymphoma. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Of the 127 children included (87 males and 40 females; median age 7 years, range 2-17), 96 had non-Hodgkin's lymphoma (46 Burkitt's lymphoma and 50 other non-Hodgkin's lymphoma), 31 had chronic inflammatory conditions, and only 10% were HIV-positive. The most common clinical presentations for all disease categories considered were fever, night sweats, and weight loss. EBV viral load in whole blood was elevated in Burkitt's lymphoma compared to other non-Hodgkin's lymphoma (OR 6.67, 95% CI 1.32, 33.69; P-value = 0.04), but EBV viral loads in saliva and white blood cells were not different in any of the disease categories considered. A significant difference in EAd-IgG was observed when non-Hodgkin's lymphoma was compared with chronic inflammatory conditions (OR 0.19, 95% CI 0.07, 0.51; P-value = 0.001). When compared to chronic inflammatory conditions, EBV viral load was elevated in Burkitt's lymphoma, and EA IgG was higher in non-Hodgkin's lymphoma. This study supports an association between virological and serological markers of EBV and childhood non-Hodgkin's lymphoma, irrespective of subtype, in Uganda. © 2014 Wiley Periodicals, Inc.

Serologic Evidence of Previous Campylobacter jejuni Infection in Patients with the Guillain-Barre Syndrome

DTIC Science & Technology

1993-06-15

chronic inflammatory demyelinating polyneuropathy , and polyneuropathy associated with IgM paraproteinemia. creased the sensitivity but improved the...paraproteine- were employees of or visitors to the Infectious Diseases Divi- ,,i- hronic inflammatory demyelinating polyneuropathy , sion of Vanderbilt... polyneuropathy ," is an inflammatory de- jejuni infection before onset of neurologic symptoms. myelinating disease of peripheral nerves characterized

Clinically granulomatous cheilitis with plasma cells

PubMed Central

Sarkar, Somenath; Ghosh, Sarmistha; Sengupta, Dipayan

2016-01-01

Plasma cell cheilitis, also known as plasma cell orificial mucositis is a benign inflammatory condition clinically characterized by erythematous plaque on lips that may be ulcerated. Histopathologically it is characterized by dense plasma cell infiltrates in a band-like pattern in dermis, which corresponds to Zoon's plasma cell balanitis. On the other hand, granulomatous cheilitis, as a part of orofacial granulomatosis, manifests as sudden diffuse or nodular swelling involving lip and cheek. Initial swelling is soft to firm, but with recurrent episodes swelling gradually become firm rubbery in consistency. We hereby report a case of cheilitis in a 52-year-old man with diffuse swelling involving lower lip, which clinically resembles granulomatous cheilitis, but histopathological examination showed diffuse infiltrate of plasma cells predominantly in upper and mid-dermis. PMID:27057489

Successful treatment of an unresectable inflammatory myofibroblastic tumor of the frontal bone using a cyclooxygenase-2 inhibitor and methotrexate.

PubMed

Kusunoki-Nakamoto, Fumiko; Matsukawa, Takashi; Tanaka, Masaki; Miyagawa, Toji; Yamamoto, Tomotaka; Shimizu, Jun; Ikemura, Masako; Shibahara, Junji; Tsuji, Shoji

2013-01-01

Inflammatory myofibroblastic tumor (IMT) is a disease characterized by tumorous lesions consisting of myofibroblastic spindle cells and inflammatory cells that occur primarily in the soft tissues and viscera of children and young adults. Total excision is the most effective therapy. Steroids have been used to treat unresectable lesions with some success. We herein report a case of IMT involving the frontal bone accompanied by pachymeningitis. The tumor was characterized by an aggressive clinical course that was refractory to prednisolone. Performing total excision seemed difficult. Celecoxib and methotrexate were effective treatments. Our experience suggests the efficacy of celecoxib and methotrexate as alternatives for treating unresectable IMT.

Effects of simulated inflammation on the corrosion of 316L stainless steel.

PubMed

Brooks, Emily K; Brooks, Richard P; Ehrensberger, Mark T

2017-02-01

Stainless steel alloys, including 316L, find use in orthopaedics, commonly as fracture fixation devices. Invasive procedures involved in the placement of these devices will provoke a local inflammatory response that produces hydrogen peroxide (H 2 O 2 ) and an acidic environment surrounding the implant. This study assessed the influence of a simulated inflammatory response on the corrosion of 316L stainless steel. Samples were immersed in an electrolyte representing either normal or inflammatory physiological conditions. After 24h of exposure, electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to evaluate differences in corrosion behavior and ion release induced by the inflammatory conditions. Scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX) were used to evaluate surface morphology and corrosion products formed on the sample surface. Inflammatory conditions, involving the presence of H 2 O 2 and an acidic pH, significantly alter the corrosion processes of 316L stainless steel, promoting aggressive and localized corrosion. It is demonstrated that particular consideration should be given to 316L stainless steel implants with crevice susceptible areas (ex. screw-head/plate interface), as those areas may have an increased probability of rapid and aggressive corrosion when exposed to inflammatory conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Albumin coatings by alternating current electrophoretic deposition for improving corrosion resistance and bioactivity of titanium implants.

PubMed

Höhn, Sarah; Braem, Annabel; Neirinck, Bram; Virtanen, Sannakaisa

2017-04-01

Although Ti alloys are generally regarded to be highly corrosion resistant, inflammatory conditions following surgery can instigate breakdown of the TiO 2 passivation layer leading to an increased metal ion release. Furthermore proteins present in the surrounding tissue will readily adsorb on a titanium surface after implantation. In this paper alternating current electrophoretic deposition (AC-EPD) of bovine serum albumin (BSA) on Ti6Al4V was investigated in order to increase the corrosion resistance and control the protein adsorption capability of the implant surface. The Ti6Al4V surface was characterized with SEM, XPS and ToF-SIMS after long-term immersion tests under physiological conditions and simulated inflammatory conditions either in Dulbecco's Modified Eagle Medium (DMEM) or DMEM supplemented with fetal calf serum (FCS). The analysis showed an increased adsorption of amino acids and proteins from the different immersion solutions. The BSA coating was shown to prevent selective dissolution of the vanadium (V) rich β-phase, thus effectively limiting metal ion release to the environment. Electrochemical impedance spectroscopy measurements confirmed an increase of the corrosion resistance for BSA coated surfaces as a function of immersion time due to the time-dependent adsorption of the different amino acids (from DMEM) and proteins (from FCS) as observed by ToF-SIMS analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Circadian disruption promotes tumor growth by anabolic host metabolism; experimental evidence in a rat model.

PubMed

Guerrero-Vargas, Natalí N; Navarro-Espíndola, Raful; Guzmán-Ruíz, Mara A; Basualdo, María Del Carmen; Espitia-Bautista, Estefania; López-Bago, Ana; Lascurain, Ricardo; Córdoba-Manilla, Cinthya; Buijs, Ruud M; Escobar, Carolina

2017-09-06

Light at night creates a conflicting signal to the biological clock and disrupts circadian physiology. In rodents, light at night increases the risk to develop mood disorders, overweight, disrupted energy metabolism, immune dysfunction and cancer. We hypothesized that constant light (LL) in rats may facilitate tumor growth via disrupted metabolism and increased inflammatory response in the host, inducing a propitious microenvironment for tumor cells. Male Wistar rats were exposed to LL or a regular light-dark cycle (LD) for 5 weeks. Body weight gain, food consumption, triglycerides and glucose blood levels were evaluated; a glucose tolerance test was also performed. Inflammation and sickness behavior were evaluated after the administration of intravenous lipopolysaccharide. Tumors were induced by subcutaneous inoculation of glioma cells (C6). In tumor-bearing rats, the metabolic state and immune cells infiltration to the tumor was investigated by using immunohistochemistry and flow cytometry. The mRNA expression of genes involved metabolic, growth, angiogenes and inflammatory pathways was measured in the tumor microenvironment by qPCR. Tumor growth was also evaluated in animals fed with a high sugar diet. We found that LL induced overweight, high plasma triglycerides and glucose levels as well as reduced glucose clearance. In response to an LPS challenge, LL rats responded with higher pro-inflammatory cytokines and exacerbated sickness behavior. Tumor cell inoculation resulted in increased tumor volume in LL as compared with LD rats, associated with high blood glucose levels and decreased triglycerides levels in the host. More macrophages were recruited in the LL tumor and the microenvironment was characterized by upregulation of genes involved in lipogenesis (Acaca, Fasn, and Pparγ), glucose uptake (Glut-1), and tumor growth (Vegfα, Myc, Ir) suggesting that LL tumors rely on these processes in order to support their enhanced growth. Genes related with the inflammatory state in the tumor microenvironment were not different between LL and LD conditions. In rats fed a high caloric diet tumor growth was similar to LL conditions. Data indicates that circadian disruption by LL provides a favorable condition for tumor growth by promoting an anabolic metabolism in the host.

Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

NASA Astrophysics Data System (ADS)

Hu, Wenyan; Fu, Ling

2013-05-01

Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (p<0.001, analysis of variance linear contrast; n=8 for each group). Pathological events relating to these components were observed, including presence of inflammatory cells, deposited collagen, and phenotype conversion of PSCs. We demonstrate that label-free nonlinear optical microscopy is an efficient tool for dissecting PSCs and other pancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

Mutual inhibition between HDAC9 and miR-17 regulates osteogenesis of human periodontal ligament stem cells in inflammatory conditions.

PubMed

Li, Liya; Liu, Wenjia; Wang, Hong; Yang, Qianjuan; Zhang, Liqiang; Jin, Fang; Jin, Yan

2018-04-24

Histone deacetylases (HDAC) plays important roles in the post-translational modifications of histone cores as well as non-histone targets. Many of them are involved in key inflammatory processes. Despite their importance, whether and how HDAC9 is regulated under inflammatory conditions remains unclear. The aim of this study was to evaluate the effects of HDAC9 under chronic inflammation condition in human periodontal ligament stromal cell (PDLSCs) and to explore the underlying regulatory mechanism. PDLSCs from healthy or periodontitis human tissue was compared. The therapeutic effects of HDAC inhibitors was determined in PDLSC pellet transplanted nude mice and LPS-induced rat periodontitis. We report that HDAC9 was the most affected HDAC family member under inflammatory conditions in PDLSCs. HDAC9 impaired osteogenic differentiation capacity of PDLSCs under inflammatory conditions. Downregulation of HDAC9 by HDAC inhibitors or si-HDAC9 rescued the osteogenic differentiation capacity of inflammatory PDLSC to a similar level with the healthy PDLSC. In this context, HDAC9 and miR-17 formed an inhibitory loop. The inhibition of miR-17 aggravated loss of calcified nodules in inflamed PDLSCs and interrupted the effect of HDAC inhibitor in rescuing osteogenesis. In vivo experiments using nude mice and LPS-induced periodontitis model confirmed that HDAC inhibitors could improve new bone formation. We conclude that HDAC inhibitors improved osteogenesis of PDLSCs in vitro and periodontitis in vivo.

Principal components derived from CSF inflammatory profiles predict outcome in survivors after severe traumatic brain injury.

PubMed

Kumar, Raj G; Rubin, Jonathan E; Berger, Rachel P; Kochanek, Patrick M; Wagner, Amy K

2016-03-01

Studies have characterized absolute levels of multiple inflammatory markers as significant risk factors for poor outcomes after traumatic brain injury (TBI). However, inflammatory marker concentrations are highly inter-related, and production of one may result in the production or regulation of another. Therefore, a more comprehensive characterization of the inflammatory response post-TBI should consider relative levels of markers in the inflammatory pathway. We used principal component analysis (PCA) as a dimension-reduction technique to characterize the sets of markers that contribute independently to variability in cerebrospinal (CSF) inflammatory profiles after TBI. Using PCA results, we defined groups (or clusters) of individuals (n=111) with similar patterns of acute CSF inflammation that were then evaluated in the context of outcome and other relevant CSF and serum biomarkers collected days 0-3 and 4-5 post-injury. We identified four significant principal components (PC1-PC4) for CSF inflammation from days 0-3, and PC1 accounted for the greatest (31%) percentage of variance. PC1 was characterized by relatively higher CSF sICAM-1, sFAS, IL-10, IL-6, sVCAM-1, IL-5, and IL-8 levels. Cluster analysis then defined two distinct clusters, such that individuals in cluster 1 had highly positive PC1 scores and relatively higher levels of CSF cortisol, progesterone, estradiol, testosterone, brain derived neurotrophic factor (BDNF), and S100b; this group also had higher serum cortisol and lower serum BDNF. Multinomial logistic regression analyses showed that individuals in cluster 1 had a 10.9 times increased likelihood of GOS scores of 2/3 vs. 4/5 at 6 months compared to cluster 2, after controlling for covariates. Cluster group did not discriminate between mortality compared to GOS scores of 4/5 after controlling for age and other covariates. Cluster groupings also did not discriminate mortality or 12 month outcomes in multivariate models. PCA and cluster analysis establish that a subset of CSF inflammatory markers measured in days 0-3 post-TBI may distinguish individuals with poor 6-month outcome, and future studies should prospectively validate these findings. PCA of inflammatory mediators after TBI could aid in prognostication and in identifying patient subgroups for therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

Psoriasis: classical and emerging comorbidities*

PubMed Central

de Oliveira, Maria de Fátima Santos Paim; Rocha, Bruno de Oliveira; Duarte, Gleison Vieira

2015-01-01

Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis. PMID:25672294

Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study

PubMed Central

Leek, Jeffrey T.; Maier, Ronald V.; Tompkins, Ronald G.; Storey, John D.

2011-01-01

Background Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition. Methods and Findings We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40–80 h window post-injury. Conclusions The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions. Trial Registration ClinicalTrials.gov NCT00257231 Please see later in the article for the Editors' Summary PMID:21931541

Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2018-06-08

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Bone marrow-derived macrophages from aged rats are more responsive to inflammatory stimuli.

PubMed

Barrett, James P; Costello, Derek A; O'Sullivan, Joan; Cowley, Thelma R; Lynch, Marina A

2015-04-09

Lipopolysaccharide (LPS) and interferon-γ (IFNγ) increase expression of tumour necrosis factor-α (TNFα) that characterizes the M1 activation state of macrophages. Whereas it is accepted that the immune system undergoes changes with age, there is inconsistency in the literature with respect to the impact of age on the response of macrophages to inflammatory stimuli. Here, we investigate the effect of age on the responsiveness of bone marrow-derived macrophages (BMDMs) to LPS and IFNγ. The context for addressing this question is that macrophages, which infiltrate the brain of aged animals, will encounter the neuroinflammatory environment that has been described with age. Brain tissue, prepared from young and aged rats, was assessed for expression of inflammatory markers by PCR and for evidence of infiltration of macrophages by flow cytometry. BMDMs were prepared from the long bones of young and aged rats, maintained in culture for 8 days and incubated in the presence or absence of LPS (100 ng/ml) or IFNγ (50 ng/ml). Cells were harvested and assessed for mRNA expression of markers of M1 activation including TNFα and NOS2, or for expression of IFNγR1 and TLR4 by western immunoblotting. To assess whether BMDMs induced glial activation, mixed glial cultures were incubated in the presence of conditioned media obtained from unstimulated BMDMs of young and aged rats and evaluated for expression of inflammatory markers. Markers associated with M1 activation were expressed to a greater extent in BMDMs from aged rats in response to LPS and IFNγ, compared with cells from young rats. The increased responsiveness was associated with increases in IFNγ receptor (IFNγR) and Toll-like receptor 4 (TLR4). The data show that conditioned media from BMDMs of aged rats increased the expression of pro-inflammatory mediators in glial cells. Significantly, there was an age-related increase in macrophage infiltration into the brain, and this was combined with increased expression of IFNγ and the Toll-like receptor 4 agonist, high-mobility group protein B1 (HMGB1). Exposure of infiltrating macrophages to the inflammatory microenvironment that develops in the brain with age is likely to contribute to a damaging cascade that negatively impacts neuronal function.

Induction of Pro-Inflammatory Response via Activated Macrophage-Mediated NF-κB and STAT3 Pathways in Gastric Cancer Cells.

PubMed

Zhou, Yujuan; Xia, Longzheng; Liu, Qiang; Wang, Heran; Lin, Jingguan; Oyang, Linda; Chen, Xiaoyan; Luo, Xia; Tan, Shiming; Tian, Yutong; Su, Min; Wang, Ying; Chen, Pan; Wu, Yang; Wang, Hui; Liao, Qianjin

2018-06-19

Chronic inflammation plays an important role in the initiation and progression of gastric cancer (GC). However, the role and relationship of activated macrophages with gastric mucous epithelium cells in initiating and maintaining the inflammatory process during gastric carcinogenesis remains unclear. The tumour associated macrophages (TAMs) density of gastric cancer was characterized by immunohistochemistry, and the relationship between macrophages and gastric epithelium cells was analysed using an in vitro culture system that imitates the inflammatory microenvironment. The production of pro-inflammatory cytokines was detected by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR). MTT assays, Western blotting, qRT-PCR, and luciferase reporter assays were used to detect the effects of cell proliferation, as well as the NF-κB and STAT3 signalling pathways. TAMs infiltrated with a high intensity in GC and were significantly correlated with histology grade (P = 0.012), metastasis (P = 0.001), TNM stage (P = 0.002), and poor prognosis in patients (PFS, P = 0.005; OS, P = 0.028). In addition, IL-6 and IL-8 were elevated in the serum of GC patients and significantly promoted the growth of GC. The exposure of BGC823 gastric cancer cells to a conditioned medium from LPS-treated D-THP-1 cells significantly induced the production of TNF-α, IL-6, IL-1β and IL-8 (P< 0.01). LPS and LPS-treated D-THP-1-conditioned media promoted gastric cancer cell proliferation and triggered the significant activation of NF-κB and STAT3 with a concomitant degradation of IκBα and an increase in JAK2 phosphorylation (P < 0.05). Moreover, gastric cancer cells markedly expressed cell membrane LPS receptors, such as TLR1, TLR4, TLR6, CD14 and MD2. TAMs are closely associated with the growth of GC and prognosis in GC patients. GC cells may directly sustain and amplify the local pro-inflammatory response upon encountering activated macrophages and LPS via NF-κB and STAT3 signalling pathways, thereby promoting tumour progression. © 2018 The Author(s). Published by S. Karger AG, Basel.

Defining intrinsic vs. extrinsic atopic dermatitis.

PubMed

Karimkhani, Chante; Silverberg, Jonathan I; Dellavalle, Robert P

2015-06-16

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin condition characterized by eczematous lesions, i.e. ill-demarcated erythematous patches and plaques. AD is commonly associated with elevated immunoglobulin E (IgE) and atopic disorders, such as asthma, hay fever, and food allergies. Rackemann and Mallory were some of the first to distinguish between asthma based on the presence ("extrinsic") or absence ("intrinsic") of allergy. This distinction has subsequently been applied to AD based on the presence ("extrinsic") or absence ("intrinsic") of increased IgE and atopic disease. Although the distinction between intrinsic and extrinsic AD is widely used, it remains controversial.

The Charcot Foot in Diabetes

PubMed Central

Frykberg, Robert G.; Armstrong, David G.; Boulton, Andrew J.M.; Edmonds, Michael; Van, Georges Ha; Hartemann, Agnes; Game, Frances; Jeffcoate, William; Jirkovska, Alexandra; Jude, Edward; Morbach, Stephan; Morrison, William B.; Pinzur, Michael; Pitocco, Dario; Sanders, Lee; Wukich, Dane K.; Uccioli, Luigi

2011-01-01

The diabetic Charcot foot syndrome is a serious and potentially limb-threatening lower-extremity complication of diabetes. First described in 1883, this enigmatic condition continues to challenge even the most experienced practitioners. Now considered an inflammatory syndrome, the diabetic Charcot foot is characterized by varying degrees of bone and joint disorganization secondary to underlying neuropathy, trauma, and perturbations of bone metabolism. An international task force of experts was convened by the American Diabetes Association and the American Podiatric Medical Association in January 2011 to summarize available evidence on the pathophysiology, natural history, presentations, and treatment recommendations for this entity. PMID:21868781

Eosinophilic pustular folliculitis in infancy: report of a new case.

PubMed

Alonso-Castro, L; Pérez-García, B; González-García, C; Jaén-Olasolo, P

2012-10-15

We report a new case of eosinophilic pustular folliculitis in a 23-month-old boy. He presented with a seven-month history of recurrent episodes of pustular lesions on the scalp after having been treated with oral antifungal and topic antibiotics without response. The diagnosis was based on the clinical course and typical histopathological findings. Eosinophilic pustular folliculitis in infancy is an idiopathic and rare inflammatory disease characterized by recurrent crops of sterile pustules involving mainly the scalp. Because it is a benign, self-limiting condition an accurate diagnosis is essential to avoid unnecessary therapies.

Antioxidant airway responses following experimental exposure to wood smoke in man

PubMed Central

2010-01-01

Background Biomass combustion contributes to the production of ambient particulate matter (PM) in rural environments as well as urban settings, but relatively little is known about the health effects of these emissions. The aim of this study was therefore to characterize airway responses in humans exposed to wood smoke PM under controlled conditions. Nineteen healthy volunteers were exposed to both wood smoke, at a particulate matter (PM2.5) concentration of 224 ± 22 μg/m3, and filtered air for three hours with intermittent exercise. The wood smoke was generated employing an experimental set-up with an adjustable wood pellet boiler system under incomplete combustion. Symptoms, lung function, and exhaled NO were measured over exposures, with bronchoscopy performed 24 h post-exposure for characterisation of airway inflammatory and antioxidant responses in airway lavages. Results Glutathione (GSH) concentrations were enhanced in bronchoalveolar lavage (BAL) after wood smoke exposure vs. air (p = 0.025), together with an increase in upper airway symptoms. Neither lung function, exhaled NO nor systemic nor airway inflammatory parameters in BAL and bronchial mucosal biopsies were significantly affected. Conclusions Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure. PMID:20727160

Fluoxetine treatment affects the inflammatory response and microglial function according to the quality of the living environment.

PubMed

Alboni, Silvia; Poggini, Silvia; Garofalo, Stefano; Milior, Giampaolo; El Hajj, Hassan; Lecours, Cynthia; Girard, Isabelle; Gagnon, Steven; Boisjoly-Villeneuve, Samuel; Brunello, Nicoletta; Wolfer, David P; Limatola, Cristina; Tremblay, Marie-Ève; Maggi, Laura; Branchi, Igor

2016-11-01

It has been hypothesized that selective serotonin reuptake inhibitors (SSRIs), the most common treatment for major depression, affect mood through changes in immune function. However, the effects of SSRIs on inflammatory response are contradictory since these act either as anti- or pro-inflammatory drugs. Previous experimental and clinical studies showed that the quality of the living environment moderates the outcome of antidepressant treatment. Therefore, we hypothesized that the interplay between SSRIs and the environment may, at least partially, explain the apparent incongruence regarding the effects of SSRI treatment on the inflammatory response. In order to investigate such interplay, we exposed C57BL/6 mice to chronic stress to induce a depression-like phenotype and, subsequently, to fluoxetine treatment or vehicle (21days) while being exposed to either an enriched or a stressful condition. At the end of treatment, we measured the expression levels of several anti- and pro-inflammatory cytokines and inflammatory mediators in the whole hippocampus and in isolated microglia. We also determined microglial density, distribution, and morphology to investigate their surveillance state. Results show that the effects of fluoxetine treatment on inflammation and microglial function, as compared to vehicle, were dependent on the quality of the living environment. In particular, fluoxetine administered in the enriched condition increased the expression of pro-inflammatory markers compared to vehicle, while treatment in a stressful condition produced anti-inflammatory effects. These findings provide new insights regarding the effects of SSRIs on inflammation, which may be crucial to devise pharmacological strategies aimed at enhancing antidepressant efficacy by means of controlling environmental conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Adipose stromal cells primed with hypoxia and inflammation enhance cardiomyocyte proliferation rate in vitro through STAT3 and Erk1/2

PubMed Central

2013-01-01

Background Experimental clinical stem cell therapy has been used for more than a decade to alleviate the adverse aftermath of acute myocardial infarction (aMI). The post-infarcted myocardial microenvironment is characterized by cardiomyocyte death, caused by ischemia and inflammation. These conditions may negatively affect administered stem cells. As postnatal cardiomyocytes have a poor proliferation rate, while induction of proliferation seems even more rare. Thus stimulation of their proliferation rate is essential after aMI. In metaplastic disease, the pro-inflammatory cytokine interleukin-6 (IL-6) has been identified as potent mediators of the proliferation rate. We hypothesized that IL-6 could augment the proliferation rate of (slow-)dividing cardiomyocytes. Methods To mimic the behavior of therapeutic cells in the post-infarct cardiac microenvironment, human Adipose Derived Stromal Cells (ADSC) were cultured under hypoxic (2% O2) and pro-inflammatory conditions (IL-1β) for 24h. Serum-free conditioned medium from ADSC primed with hypoxia and/or IL-1β was added to rat neonatal cardiomyocytes and adult cardiomyocytes (HL-1) to assess paracrine-driven changes in cardiomyocyte proliferation rate and induction of myogenic signaling pathways. Results We demonstrate that ADSC enhance the proliferation rate of rat neonatal cardiomyocytes and adult HL-1 cardiomyocytes in a paracrine fashion. ADSC under hypoxia and inflammation in vitro had increased the interleukin-6 (IL-6) gene and protein expression. Similar to conditioned medium of ADSC, treatment of rat neonatal cardiomyocytes and HL-1 with recombinant IL-6 alone also stimulated their proliferation rate. This was corroborated by a strong decrease of cardiomyocyte proliferation after addition of IL-6 neutralizing antibody to conditioned medium of ADSC. The stimulatory effect of ADSC conditioned media or IL-6 was accomplished through activation of both Janus Kinase-Signal Transducer and Activator of Transcription (JAK/STAT) and Mitogen-Activated Protein (MAP) kinases (MAPK) mitogenic signaling pathways. Conclusion ADSC are promising therapeutic cells for cardiac stem cell therapy. The inflammatory and hypoxic host post-MI microenvironment enhances the regenerative potential of ADSC to promote the proliferation rate of cardiomyocytes. This was achieved in paracrine manner, which warrants the development of ADSC conditioned medium as an “of-the-shelf” product for treatment of post-myocardial infarction complications. PMID:23406316

Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Primer for Internists.

PubMed

Syal, Gaurav; Kashani, Amir; Shih, David Q

2018-03-29

Inflammatory bowel disease consists of disorders characterized by chronic idiopathic bowel inflammation. The concept of host-gut-microbiome interaction in the pathogenesis of various complex immune-mediated chronic diseases, including inflammatory bowel disease, has recently generated immense interest. Mounting evidence confirms alteration of intestinal microflora in patients with inflammatory bowel disease. Thus, restoration of normal gut microbiota has become a focus of basic and clinical research in recent years. Fecal microbiota transplantation is being explored as one such therapeutic strategy and has shown encouraging results in the management of patients with inflammatory bowel disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Tumor necrosis factor alpha converting enzyme: an encouraging target for various inflammatory disorders.

PubMed

Bahia, Malkeet S; Silakari, Om

2010-05-01

Tumor necrosis factor alpha is one of the most common pro-inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti-tumor necrosis factor alpha antibodies like Enbrel, Humira and Remicade have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side-effects can be over-ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.

Ubiquitination in Periodontal Disease: A Review.

PubMed

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-07-10

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue's response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin-protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases.

Ubiquitination in Periodontal Disease: A Review

PubMed Central

Tsuchida, Sachio; Satoh, Mamoru; Takiwaki, Masaki; Nomura, Fumio

2017-01-01

Periodontal disease (periodontitis) is a chronic inflammatory condition initiated by microbial infection that leads to gingival tissue destruction and alveolar bone resorption. The periodontal tissue’s response to dental plaque is characterized by the accumulation of polymorphonuclear leukocytes, macrophages, and lymphocytes, all of which release inflammatory mediators and cytokines to orchestrate the immunopathogenesis of periodontal disease. Ubiquitination is achieved by a mechanism that involves a number of factors, including an ubiquitin-activating enzyme, ubiquitin-conjugating enzyme, and ubiquitin–protein ligase. Ubiquitination is a post-translational modification restricted to eukaryotes that are involved in essential host processes. The ubiquitin system has been implicated in the immune response, development, and programmed cell death. Increasing numbers of recent reports have provided evidence that many approaches are delivering promising reports for discovering the relationship between ubiquitination and periodontal disease. The scope of this review was to investigate recent progress in the discovery of ubiquitinated protein in diseased periodontium and to discuss the ubiquitination process in periodontal diseases. PMID:28698506

TGF-β in inflammatory bowel disease: a key regulator of immune cells, epithelium, and the intestinal microbiota.

PubMed

Ihara, Sozaburo; Hirata, Yoshihiro; Koike, Kazuhiko

2017-07-01

Inflammatory bowel disease (IBD) is defined as chronic intestinal inflammation, and includes ulcerative colitis and Crohn's disease. Multiple factors are involved in the pathogenesis of IBD, and the condition is characterized by aberrant mucosal immune reactions to intestinal microbes in genetically susceptible hosts. Transforming growth factor-β (TGF-β) is an immune-suppressive cytokine produced by many cell types and activated by integrins. Active TGF-β binds to its receptor and regulates mucosal immune reactions through the TGF-β signaling pathway. Dysregulated TGF-β signaling is observed in the intestines of IBD patients. TGF-β signal impairment in specific cell types, such as T-cells and dendritic cells, results in spontaneous colitis in mouse models. In addition, specific intestinal microbes contribute to immune homeostasis by modulating TGF-β production. In this review, we describe the role of TGF-β in intestinal immunity, focusing on immune cells, epithelium, and intestinal microbes. In addition, we present potential therapeutic strategies for IBD that target TGF-β.

Capillary electrochromatography and capillary electrochromatography-electrospray mass spectrometry for the separation of non-steroidal anti-inflammatory drugs.

PubMed

Desiderio, C; Fanali, S

2000-10-20

In this study capillary electrochromatography (CEC) was utilized for the separation of ten non-steroidal anti-inflammatory drugs (NSAIDs). Experiments were carried out in a commercially available CE instrument using a packed capillary with RP-18 silica particles where the stationary phase completely filled the capillary. The mobile phase consisted of a mixture of ammonium formate buffer pH 2.5 and acetonitrile. Selectivity and resolution were studied changing the pH and the concentration of the buffer, the acetonitrile content mobile phase and the capillary temperature. The optimum experimental conditions for CEC separation of the studied drug mixture were found using 50 mM ammonium formate pH 2.5-acetonitrile (40:60) at 25 degrees C. The CEC capillary was coupled to an electrospray mass spectrometer for the characterization of the NSAIDs. A mobile phase composed by the same buffer but with a higher concentration of acetonitrile (90%) was used in order to speed up the separation of analytes.

[Pleomorphic carcinoma of the lung with high serum granulocyte colony stimulating factor, suggested of pulmonary abscess by preoperative radiology; report of a case].

PubMed

Mizuno, Mikoto; Miyoshi, Tatsu; Nabeshima, Kazuki; Iwasaki, Akinori; Shirakusa, Takaho

2006-08-01

A 52-year-old man with a history of heavy smoking was hospitalized for evaluation of fever. Pulmonary abscess was initially suspected by computed tomography (CT) showing an ovoid, well-demarcated nodule of 61 mm in diameter with coarse calcification in S2a of the right lung. The patient was treated with antibiotics, but no improvement was seen in inflammatory reactions or lesion size. Marked leukocytosis and high level of granulocyte colony stimulating factor (G-CSF) was shown by laboratory examination. To improve patient condition and ensure correct diagnosis, right upper lobectomy of the lung was performed. Pleomorphic carcinoma of the lung was subsequently diagnosed. G-CSF producing tumor was suspected, since the normalization of serum G-CSF level followed by the improvement of both fever and inflammatory reaction was observed postoperatively. We also present herein a review of 22 Japanese cases of pleomorphic carcinoma producing G-CSF of the lung, characterized by leukocytosis.

Resolution of inflammation by interleukin-9-producing type 2 innate lymphoid cells

PubMed Central

Rauber, Simon; Luber, Markus; Weber, Stefanie; Maul, Lisa; Soare, Alina; Wohlfahrt, Thomas; Lin, Neng-Yu; Dietel, Katharina; Bozec, Aline; Herrmann, Martin; Kaplan, Mark H.; Weigmann, Benno; Zaiss, Mario M.; Fearon, Ursula; Veale, Douglas J.; Canete, Juan D.; Distler, Oliver; Rivellese, Felice; Pitzalis, Costantino; Neurath, Markus F.; McKenzie, Andrew N.J.; Wirtz, Stefan; Schett, Georg; Distler, Jörg H.W.; Ramming, Andreas

2017-01-01

Inflammatory diseases such as arthritis are chronic conditions that fail to resolve spontaneously. While the cytokine and cellular pathways triggering arthritis are well defined, those responsible for the resolution of inflammation are incompletely characterized. Here we identified IL-9-producing type 2 innate lymphoid cells (ILC2s) as a molecular and cellular pathway that orchestrates the resolution of chronic inflammation. In mice, the absence of IL-9 impaired ILC2 proliferation, activation of regulatory T cells (Treg) and resulted in chronic arthritis with excessive cartilage destruction and bone loss. In contrast, treatment with IL-9 promoted ILC2-dependent Treg activation and effectively induced resolution of inflammation and protection of bone. Rheumatoid arthritis patients in remission demonstrated high numbers of IL-9+ ILC2s in the joints and in the circulation. Hence, fostering IL-9-mediated ILC2 activation may offer a novel therapeutic approach inducing resolution of inflammation rather than suppression of inflammatory responses. PMID:28714991

Neutrophil subset responses in infants with severe viral respiratory infection.

PubMed

Cortjens, Bart; Ingelse, Sarah A; Calis, Job C; Vlaar, Alexander P; Koenderman, Leo; Bem, Reinout A; van Woensel, Job B

2017-03-01

Neutrophils are the predominant inflammatory cells recruited to the respiratory tract as part of the innate immune response to viral infections. Recent reports indicate the existence of distinct functional neutrophil subsets in the circulatory compartment of adults, following severe inflammatory conditions. Here, we evaluated the occurrence of neutrophil subsets in blood and broncho-alveolar lavage fluid during severe viral respiratory infection in infants based on CD16/CD62L expression. We show that during the course of severe respiratory infection infants may develop four heterogeneous neutrophil subsets in blood (mature, immature, progenitor, and suppressive neutrophils), each with distinct activation states. However, while isolated viral respiratory infection was characterized by a relative absence of suppressive neutrophils in both blood and lungs, only patients with bacterial co-infection were shown to produce suppressive neutrophils. These data suggest the occurrence of distinct and unique neutrophil subset responses during severe viral and (secondary) bacterial respiratory infection in infants. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design and environmentally benign synthesis of novel thiophene appended pyrazole analogues as anti-inflammatory and radical scavenging agents: Crystallographic, in silico modeling, docking and SAR characterization.

PubMed

Prabhudeva, Malledevarapura Gurumurthy; Bharath, Srinivasan; Kumar, Achutha Dileep; Naveen, Shivalingegowda; Lokanath, Neratur Krishnappagowda; Mylarappa, Bantaganahalli Ningappa; Kumar, Kariyappa Ajay

2017-08-01

Oxidative-stress induces inflammatory diseases and infections caused by drug-resistant microbial strains are on the rise necessitating the discovery of novel small-molecules for intervention therapy. The current study presents an effective and new green protocol for the synthesis of thiophene-appended pyrazoles through 3+2 annulations method. Chalcones 3(a-g) were prepared from 5-chloro-2-acetylthiophene and aromatic aldehydes by Claisen-Schmidt approach. The reaction of chalcones 3(a-g) with phenylhydrazine hydrochlorides 4(a-b) in acetic acid (30%) medium and also with freshly prepared citrus extract medium under reflux conditions produced the thiophene appended pyrazoles 5(a-l) in moderate yields. Structures of synthesized new pyrazoles were confirmed by spectral studies, elemental analysis and single crystal X-ray diffraction studies. Further, preliminary assessment of the anti-inflammatory properties of the compounds showed that, amongst the series, compounds 5d, 5e and 5l have excellent anti-inflammatory activities. Further, compounds 5c, 5d, 5g, and 5i exhibited excellent DPPH radical scavenging abilities in comparison with the standard ascorbic acid. Furthermore, using detailed structural modeling and docking efforts, combined with preliminary SAR, we show possible structural and chemical features on both the small-molecules and the protein that might contribute to the binding and inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

Pentagalloyl glucose increases elastin deposition, decreases reactive oxygen species and matrix metalloproteinase activity in pulmonary fibroblasts under inflammatory conditions.

PubMed

Parasaram, Vaideesh; Nosoudi, Nasim; Chowdhury, Aniqa; Vyavahare, Naren

2018-04-30

Emphysema is characterized by degradation of lung alveoli that leads to poor airflow in lungs. Irreversible elastic fiber degradation by matrix metalloproteinases (MMPs) and reactive oxygen species (ROS) activity leads to loss of elasticity and drives the progression of this disease. We investigated if a polyphenol, pentagalloyl glucose (PGG) can increase elastin production in pulmonary fibroblasts. We also studied the effect of PGG treatment in reducing MMP activity and ROS levels in cells. We exposed rat pulmonary fibroblasts to two different types of inflammatory environments i.e., tumor necrosis factor-α (TNF-α) and cigarette smoke extract (CSE) to mimic the disease. Parameters like lysyl oxidase (LOX) and elastin gene expression, MMP-9 activity in the medium, lysyl oxidase (LOX) activity and ROS levels were studied to assess the effect of PGG on pulmonary fibroblasts. CSE inhibited lysyl oxidase (LOX) enzyme activity that resulted in a decreased elastin formation. Similarly, TNF-α treated cells showed less elastin in the cell layers. Both these agents caused increase in MMP activity and ROS levels in cells. However, when supplemented with PGG treatment along with these two inflammatory agents, we saw a significant increase in elastin deposition, reduction in both MMP activity and ROS levels. Thus PGG, which has anti-inflammatory, anti-oxidant properties coupled with its ability to aid in elastic fiber formation, can be a multifunctional drug to potentially arrest the progression of emphysema. Copyright © 2018 Elsevier Inc. All rights reserved.

Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis.

PubMed

Kalinkovich, Alexander; Livshits, Gregory

2017-05-01

Sarcopenia, an age-associated decline in skeletal muscle mass coupled with functional deterioration, may be exacerbated by obesity leading to higher disability, frailty, morbidity and mortality rates. In the combination of sarcopenia and obesity, the state called sarcopenic obesity (SOB), some key age- and obesity-mediated factors and pathways may aggravate sarcopenia. This review will analyze the mechanisms underlying the pathogenesis of SOB. In obese adipose tissue (AT), adipocytes undergo hypertrophy, hyperplasia and activation resulted in accumulation of pro-inflammatory macrophages and other immune cells as well as dysregulated production of various adipokines that together with senescent cells and the immune cell-released cytokines and chemokines create a local pro-inflammatory status. In addition, obese AT is characterized by excessive production and disturbed capacity to store lipids, which accumulate ectopically in skeletal muscle. These intramuscular lipids and their derivatives induce mitochondrial dysfunction characterized by impaired β-oxidation capacity and increased reactive oxygen species formation providing lipotoxic environment and insulin resistance as well as enhanced secretion of some pro-inflammatory myokines capable of inducing muscle dysfunction by auto/paracrine manner. In turn, by endocrine manner, these myokines may exacerbate AT inflammation and also support chronic low grade systemic inflammation (inflammaging), overall establishing a detrimental vicious circle maintaining AT and skeletal muscle inflammation, thus triggering and supporting SOB development. Under these circumstances, we believe that AT inflammation dominates over skeletal muscle inflammation. Thus, in essence, it redirects the vector of processes from "sarcopenia→obesity" to "obesity→sarcopenia". We therefore propose that this condition be defined as "obese sarcopenia", to reflect the direction of the pathological pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

What People with Inflammatory Bowel Disease Need to Know about Osteoporosis

MedlinePlus

... With Inflammatory Bowel Disease Need to Know About Osteoporosis What Is Inflammatory Bowel Disease? Crohn’s disease and ... Management Strategies Resources For Your Information What Is Osteoporosis? Osteoporosis is a condition in which the bones ...

AA amyloidosis: Mount Sinai experience, 1997-2012.

PubMed

Bunker, Daniel; Gorevic, Peter

2012-01-01

AA amyloidosis is a systemic disease characterized by the extracellular deposition of amyloid fibrils derived from the acute-phase reactant serum amyloid A protein. It is typically a consequence of chronic inflammatory conditions like rheumatoid arthritis or Crohn's disease, although more patients are being identified who have more unusual causes or no known inflammatory stimulus. We performed a retrospective chart review of all patients with AA amyloidosis seen at Mount Sinai during the period of 1997-2012. Particular attention was paid to the patients' underlying diseases, extent of organ involvement, levels of inflammatory markers and proinflammatory cytokines, presence of pyrin gene mutations, and outcomes. Forty-three patients were seen at Mount Sinai with AA amyloidosis during this period. The most common underlying diseases were rheumatoid arthritis (21%) and Crohn's disease (16%), though 21% of patients were considered to have idiopathic AA amyloid after an extensive search found no underlying inflammatory disease. Almost all patients (95%) had renal involvement based on biopsy or clinical criteria, with 19 patients (44%) eventually requiring dialysis and 5 (12%) undergoing renal transplantation. Inflammatory markers were elevated in most patients; however, interleukin-6 was the only consistently elevated cytokine. Three patients (of 9 tested) were found to be positive for the E148Q pyrin gene mutation. Our study confirms the increasing number of patients being seen with idiopathic AA amyloidosis. More research is needed to determine if these patients have an underlying genetic susceptibility encoded in pyrin or other genes. Our study also confirms the dominance of renal disease in this population. The elevated levels of interleukin-6, in comparison with other cytokines, could represent a therapeutic target. © 2012 Mount Sinai School of Medicine.

Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.

Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

Epithelial Permeability Alterations in an In Vitro Air-Liquid Interface Model of Allergic Fungal Rhinosinusitis

PubMed Central

Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

2012-01-01

Background Chronic rhinosinusitis (CRS) is an inflammatory upper-airway disease with numerous etiologies. Patients with a characteristic subtype of CRS, allergic fungal rhinosinusitis (AFRS), display increased expression of Th2 cytokines and antigen-specific IgE. Various sinonasal inflammatory conditions are associated with alterations in epithelial barrier function. The aim of this study was to compare epithelial permeability and intercellular junctional protein expression amongst cultured primary sinonasal cells from AFRS patients versus non-inflammatory controls. Methods Epithelial cells isolated from paranasal sinus mucosa of AFRS and non-inflammatory control patients were grown to confluence on permeable supports and transitioned to air-liquid interface (ALI). Trans-epithelial resistance (TER) was measured with a horizontal Ussing chamber to characterize the functional permeability of each cell type. After TER recordings were complete, a panel of intercellular junctional proteins was assessed by Western blot and immunofluorescence labeling followed by confocal microscopy. Results After 12 samples were measured from each group, we observed a 41% mean decrease in TER in AFRS cells (296±89 ohms × cm2) compared to control (503±134 ohms × cm2, P=0.006). TER deficits observed in AFRS were associated with decreased expression of the tight junction proteins occludin and Junctional Adhesion Molecule-A (JAM-A), and increased expression of a leaky tight junction protein claudin-2. Conclusions Cultured sinonasal epithelium from AFRS patients displayed increased epithelial permeability and altered expression of intercellular junctional proteins. Given that these cells were not incubated with inflammatory cytokines in vitro, the cultured AFRS epithelial alterations may represent a retained modification in protein expression from the in vivo phenotype. PMID:22927233

13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis.

PubMed

Walker, Mary E; Souza, Patricia R; Colas, Romain A; Dalli, Jesmond

2017-08-01

Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins-atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)-to mice during inflammatory arthritis up-regulated systemic and tissue amounts of a novel family of proresolving mediators, termed 13-series resolvins (RvTs), and significantly reduced joint disease. Of note, administration of simvastatin (0.2 mg/kg) did not significantly up-regulate RvTs or reduce joint inflammation. We also found that atorvastatin and pravastatin each reduced systemic leukocyte activation, including platelet-monocyte aggregates (∼25-60%). These statins decreased neutrophil trafficking to the joint as well as joint monocyte and macrophage numbers. Atorvastatin and pravastatin produced significant reductions (∼30-50%) in expression of CD11b and major histocompatibility complex class II on both monocytes and monocyte-derived macrophages in joints. Administration of an inhibitor to cyclooxygenase-2, the initiating enzyme in the RvT pathway, reversed the protective actions of these statins on both joint and systemic inflammation. Together, these findings provide evidence for the role of RvTs in mediating the protective actions of atorvastatin and pravastatin in reducing local and vascular inflammation, and suggest that RvTs may be useful in measuring the anti-inflammatory actions of statins.-Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis. © The Author(s).

Surface modification of biomaterials based on high-molecular polylactic acid and their effect on inflammatory reactions of primary human monocyte-derived macrophages: perspective for personalized therapy.

PubMed

Stankevich, Ksenia S; Gudima, Alexandru; Filimonov, Victor D; Klüter, Harald; Mamontova, Evgeniya M; Tverdokhlebov, Sergei I; Kzhyshkowska, Julia

2015-06-01

Polylactic acid (PLA) based implants can cause inflammatory complications. Macrophages are key innate immune cells that control inflammation. To provide higher biocompatibility of PLA-based implants with local innate immune cells their surface properties have to be improved. In our study surface modification technique for high-molecular PLA (MW=1,646,600g/mol) based biomaterials was originally developed and successfully applied. Optimal modification conditions were determined. Treatment of PLA films with toluene/ethanol=3/7 mixture for 10min with subsequent exposure in 0.001M brilliant green dye (BGD) solution allows to entrap approximately 10(-9)mol/cm(2) model biomolecules. The modified PLA film surface was characterized by optical microscopy, SERS, FT-IR, UV and TG/DTA/DSC analysis. Tensile strain of modified films was determined as well. The effect of PLA films modified with BGD on the inflammatory reactions of primary human monocyte-derived macrophages was investigated. We developed in vitro test-system by differentiating primary monocyte-derived macrophages on a coating material. Type 1 and type 2 inflammatory cytokines (TNFα, CCL18) secretion and histological biomarkers (CD206, stabilin-1) expression were analyzed by ELISA and confocal microscopy respectively. BGD-modified materials have improved thermal stability and good mechanical properties. However, BGD modifications induced additional donor-specific inflammatory reactions and suppressed tolerogenic phenotype of macrophages. Therefore, our test-system successfully demonstrated specific immunomodulatory effects of original and modified PLA-based biomaterials, and can be further applied for the examination of improved coatings for implants and identification of patient-specific reactions to implants. Copyright © 2015. Published by Elsevier B.V.

Early Healing Events after Periodontal Surgery: Observations on Soft Tissue Healing, Microcirculation, and Wound Fluid Cytokine Levels.

PubMed

Kaner, Doğan; Soudan, Mouaz; Zhao, Han; Gaßmann, Georg; Schönhauser, Anna; Friedmann, Anton

2017-01-27

Early wound healing after periodontal surgery with or without enamel matrix derivative/biphasic calcium phosphate (EMD/BCP) was characterized in terms of soft tissue closure, changes of microcirculation, and expression of pro- and anti-inflammatory cytokines in gingival crevicular fluid/wound fluid (GCF/WF). Periodontal surgery was carried out in 30 patients (18 patients: application of EMD/BCP for regeneration of bony defects; 12 patients: surgical crown lengthening (SCL)). Healthy sites were observed as untreated controls. GCF/WF samples were collected during two post-surgical weeks. Flap microcirculation was measured using laser Doppler flowmetry (LDF). Soft tissue healing was evaluated after two weeks. GCF/WF levels of interleukin 1β (IL-1β), tumour necrosis factor (TNF-α), IL-6, and IL-10 were determined using a multiplex immunoassay. Surgery caused similar reductions of flap microcirculation followed by recovery within two weeks in both EMD/BCP and SCL groups. GCF/WF and pro-inflammatory cytokine levels were immediately increased after surgery, and returned only partially to baseline levels within the two-week observation period. Levels of IL-10 were temporarily reduced in all surgical sites. Flap dehiscence caused prolonged elevated levels of GCF/WF, IL-1β, and TNF-α. These findings show that periodontal surgery triggers an immediate inflammatory reaction corresponding to the early inflammatory phase of wound healing, and these inflammation measures are temporary in case of maintained closure of the flap. However, flap dehiscence causes prolonged inflammatory exudation from the periodontal wound. If the biological pre-conditions for periodontal wound healing are considered important for the clinical outcome, care should be taken to maintain primary closure of the flap.

Using Corticosteroids to Reshape the Gut Microbiome: Implications for Inflammatory Bowel Diseases

DOE PAGES

Huang, Edmond Y.; Inoue, Takuya; Leone, Vanessa A.; ...

2015-05-01

Introduction—Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. Here we sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Methods—Adult male C57Bl/6 mice, germ-free (GF), Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for four weeks. Fecal samples were collected for gut microbiota analysis via 16S rRNA T-RFLP and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. GF mice were conventionalized withmore » gut microbes from treated- and non-treated groups to determine their functional capacities in recipient hosts. Results—Exposure to DEX in WT mice led to substantial shifts in gut microbiota over a four-week period. Furthermore, a significant down-regulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a pro-inflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout (IL10-KO) mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pre-treated with DEX, however, ameliorated symptoms of inflammation. We conclude that commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after GC exposure. These findings underscore the notion that intestinal microbes comprise a “microbial organ” essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.« less

Compound 9a, a novel synthetic histone deacetylase inhibitor, protects against septic injury in mice by suppressing MAPK signalling

PubMed Central

Kim, So‐Jin; Baek, Ki Seon; Park, Hyun‐Ju; Jung, Young Hoon

2016-01-01

Background and Purpose Sepsis is a life‐threatening clinical condition characterized by uncontrolled inflammatory responses and is a major cause of death in intensive care units. Histone deacetylase (HDAC) inhibitors have recently exhibited anti‐inflammatory properties. MAPK phosphatase (MKP) suppresses MAPK signalling, which plays an important role in inflammatory responses. The purpose of this study was to investigate the protective mechanisms of Compound 9a, a newly synthetized HDAC inhibitor, against septic injury. Experimental Approach The anti‐inflammatory properties of Compound 9a were assayed in LPS‐stimulated RAW264.7 cells. In vivo, polymicrobial sepsis was induced in C57BL/6 mice by caecal ligation and puncture (CLP). The mice were treated with Compound 9a (i.p., 10 mg∙kg−1) 2 h before and immediately after CLP. Key Results Compound 9a inhibited the increased production of TNF‐α, IL‐6 and NO in LPS‐stimulated RAW264.7 cells. In mice with CLP, Compound 9a improved survival rate, attenuated organ injuries and decreased serum TNF‐α and IL‐6 levels. CLP increased expression of toll‐like receptor 4, phosphorylated (p)‐p38, p‐JNK and p‐ERK proteins, which was attenuated by Compound 9a. Compound 9a decreased MKP‐1 association with HDAC1 and enhanced MKP‐1 acetylation and enhanced MKP‐1 association with p‐p38 and p‐ERK. Moreover, the inhibitory effects of Compound 9a on serum cytokine levels and phosphorylation of MAPK were abolished by MKP‐1 siRNA. Conclusions and Implications Our findings suggest that Compound 9a protected against septic injury by suppressing MAPK‐mediated inflammatory signalling. PMID:26689981

Inflammatory Mediator Profiling of n-butanol Exposed Upper Airways in Individuals with Multiple Chemical Sensitivity.

PubMed

Dantoft, Thomas Meinertz; Skovbjerg, Sine; Andersson, Linus; Claeson, Anna-Sara; Lind, Nina; Nordin, Steven; Brix, Susanne

2015-01-01

Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

Antioxidant and anti-inflammatory properties of an aqueous cyanophyta extract derived from Arthrospira platensis: contribution to bioactivities by the non-phycocyanin aqueous fraction.

PubMed

Jensen, Gitte S; Attridge, Victoria L; Beaman, Joni L; Guthrie, Jesse; Ehmann, Axel; Benson, Kathleen F

2015-05-01

The goal for this work was to characterize basic biological properties of a novel Arthrospira platensis-based aqueous cyanophyta extract (ACE), enriched in the known anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor phycocyanin (PC), but also containing a high level of non-PC bioactive compounds. Antioxidant properties were tested in parallel in the Folin-Ciocalteu assay (chemical antioxidant capacity) and in the cellular antioxidant protection (CAP-e) bioassay, where both the PC and the non-PC fractions contributed to the antioxidant capacity and CAP of ACE. In contrast to the COX-2 inhibition seen in the presence of PC, the inhibition of enzymatic activity of the inflammatory mediator Lipoxygenase was associated specifically with the non-PC fraction of ACE. Inhibition of formation of reactive oxygen species (ROS) was evaluated using polymorphonuclear cells from healthy human donors. The inhibition of ROS formation was seen for both the PC and non-PC fractions, with ACE showing the most robust effect. The effects of PC, non-PC, and ACE on clotting and clot lysing was tested using a modified Euglobulin fibrinolytic assay in vitro. In the presence of PC, non-PC, and ACE, the time for clot formation and lysis was not affected; however, the clots were significantly more robust. This effect was statistically significant (p<.05) at doses between 125-500 μg/mL, and returned to baseline at lower doses. Both PC and the non-PC fraction contributed to the antioxidant properties and anti-inflammatory effects, without a negative impact on blood clotting in vitro. This suggests a potential benefit for the consumable ACE extract in assisting the reduction of inflammatory conditions.

The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions

PubMed Central

Cynis, Holger; Hoffmann, Torsten; Friedrich, Daniel; Kehlen, Astrid; Gans, Kathrin; Kleinschmidt, Martin; Rahfeld, Jens-Ulrich; Wolf, Raik; Wermann, Michael; Stephan, Anett; Haegele, Monique; Sedlmeier, Reinhard; Graubner, Sigrid; Jagla, Wolfgang; Müller, Anke; Eichentopf, Rico; Heiser, Ulrich; Seifert, Franziska; Quax, Paul H A; de Vries, Margreet R; Hesse, Isabel; Trautwein, Daniela; Wollert, Ulrich; Berg, Sabine; Freyse, Ernst-Joachim; Schilling, Stephan; Demuth, Hans-Ulrich

2011-01-01

Acute and chronic inflammatory disorders are characterized by detrimental cytokine and chemokine expression. Frequently, the chemotactic activity of cytokines depends on a modified N-terminus of the polypeptide. Among those, the N-terminus of monocyte chemoattractant protein 1 (CCL2 and MCP-1) is modified to a pyroglutamate (pE-) residue protecting against degradation in vivo. Here, we show that the N-terminal pE-formation depends on glutaminyl cyclase activity. The pE-residue increases stability against N-terminal degradation by aminopeptidases and improves receptor activation and signal transduction in vitro. Genetic ablation of the glutaminyl cyclase iso-enzymes QC (QPCT) or isoQC (QPCTL) revealed a major role of isoQC for pE1-CCL2 formation and monocyte infiltration. Consistently, administration of QC-inhibitors in inflammatory models, such as thioglycollate-induced peritonitis reduced monocyte infiltration. The pharmacologic efficacy of QC/isoQC-inhibition was assessed in accelerated atherosclerosis in ApoE3*Leiden mice, showing attenuated atherosclerotic pathology following chronic oral treatment. Current strategies targeting CCL2 are mainly based on antibodies or spiegelmers. The application of small, orally available inhibitors of glutaminyl cyclases represents an alternative therapeutic strategy to treat CCL2-driven disorders such as atherosclerosis/restenosis and fibrosis. PMID:21774078

Diterpenoid alkaloids of Aconitum laciniatum and mitigation of inflammation by 14-O-acetylneoline in a murine model of ulcerative colitis

PubMed Central

Wangchuk, Phurpa; Navarro, Severine; Shepherd, Catherine; Keller, Paul A.; Pyne, Stephen G.; Loukas, Alex

2015-01-01

Aconitum laciniatum is used in Bhutanese traditional medicine for treating various chronic infections and inflammatory conditions. We carried out in-depth isolation and characterization of the phytochemicals from the root component and determined the anti-inflammatory effects of the isolated compounds against chemically-induced colitis in mice. Five diterpenoid alkaloids - pseudaconitine, 14-veratroylpseudaconine, 14-O-acetylneoline, neoline, and senbusine A - were isolated from A. laciniatum for the first time. Two of the alkaloids were tested for anti-inflammatory properties in the TNBS-induced colitis model in mice. Various parameters were measured to assess pathology including weight loss, clinical and macroscopic scores, histological structure and IFN-γ production in the gut. Of the two alkaloids tested, 14-O-acetylneoline showed significant protection against different parameters of colitic inflammation. Compared to control mice that received TNBS alone, mice treated with 14-O-acetylneoline experienced significantly less weight loss and had significantly lower clinical scores, macroscopic pathology and grades of histological inflammation. Moreover, colonic IFN-γ mRNA levels were significantly reduced in mice that received 14-O-acetylneoline compared to control mice that received TNBS alone. This alkaloid is now considered a novel anti-colitis drug lead compound. PMID:26240038

TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

PubMed

Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

2013-12-15

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

Peripheral artery disease, redox signaling, oxidative stress - Basic and clinical aspects.

PubMed

Steven, Sebastian; Daiber, Andreas; Dopheide, Jörn F; Münzel, Thomas; Espinola-Klein, Christine

2017-08-01

Reactive oxygen and nitrogen species (ROS and RNS, e.g. H 2 O 2 , nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage). It is well known that redox biology and oxidative stress play an important role in this setting. We here discuss the major pathways of oxidative stress and redox signaling underlying the disease progression with special emphasis on the contribution of inflammatory processes. We also highlight therapeutic strategies comprising pharmacological (e.g. statins, angiotensin-converting enzyme inhibitors, phosphodiesterase inhibition) and non-pharmacological (e.g. exercise) interventions. Both of these strategies induce potent indirect antioxidant and anti-inflammatory mechanisms that may contribute to an improvement of PAD associated complications and disease progression by removing excess formation of ROS and RNS (e.g. by ameliorating primary complications such as hyperlipidemia and hypertension) as well as the normalization of the inflammatory phenotype suppressing the progression of atherosclerosis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Characterization and management of exfoliative cheilitis: a single-center experience.

PubMed

Almazrooa, Soulafa A; Woo, Sook-Bin; Mawardi, Hani; Treister, Nathaniel

2013-12-01

Exfoliative cheilitis (EC) is a rare inflammatory condition affecting the vermilion of the lips and characterized by production of a thick keratin scale. Given the limited available data, the approach to optimal management of EC remains unclear. The objective of this retrospective study was to characterize the clinical features, management, and outcomes of a series of patients with EC. Fifteen patients with a median age of 59 years and a female-to-male ratio of 2:1 were diagnosed with EC from 2000 to 2010. Parafunctional lip licking (53%) and a history of psychiatric disorders (40%) were common. Ten patients (66%) returned for follow-up, with an overall response rate (partial or complete) of 80% at a median of 2 months, most frequently associated with the use of topical calcineurin inhibitors or moisturizing agents. Management of EC with topical calcineurin inhibitors and moisturizing agents is associated with clinical improvement, but prospective trials are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

The Salivary Microbiome in Polycystic Ovary Syndrome (PCOS) and Its Association with Disease-Related Parameters: A Pilot Study

PubMed Central

Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Pieber, Thomas R.; Gorkiewicz, Gregor; Obermayer-Pietsch, Barbara

2016-01-01

Background: Polycystic ovary syndrome (PCOS) is a common female endocrine condition of unclear etiology characterized by hyperandrogenism, oligo/amenorrhoea, and polycystic ovarian morphology. PCOS is often complicated by infertility, overweight/obesity, insulin resistance, and low-grade inflammation. The gut microbiome is known to contribute to several of these conditions. Recently, an association between stool and saliva microbiome community profiles was shown, making saliva a possible convenient, non-invasive sample type for detecting gut microbiome changes in systemic disease. In this study, we describe the saliva microbiome of PCOS patients and the association of microbiome features with PCOS-related parameters. Methods: 16S rRNA gene amplicon sequencing was performed on saliva samples from 24 PCOS patients and 20 healthy controls. Data processing and microbiome analyses were conducted in mothur and QIIME. All study subjects were characterized regarding reproductive, metabolic, and inflammatory parameters. Results: PCOS patients showed a decrease in bacteria from the phylum Actinobacteria and a borderline significant shift in bacterial community composition in unweighted UniFrac analysis. No differences between patients and controls were found in alpha diversity, weighted UniFrac analysis, or on other taxonomic levels. We found no association of saliva alpha diversity, beta diversity, or taxonomic composition with serum testosterone, oligo/amenorrhoea, overweight, insulin resistance, inflammatory markers, age, or diet. Conclusions: In this pilot study, patients with PCOS showed a reduced salivary relative abundance of Actinobacteria. Reproductive and metabolic components of the syndrome were not associated with saliva microbiome parameters, indicating that the majority of between-subject variation in saliva microbiome profiles remains to be explained. PMID:27610099

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

T-lymphocyte and cytokine expression in human inflammatory periapical lesions.

PubMed

de Brito, Luciana Carla Neves; Teles, Flávia Rocha Fonseca; Teles, Ricardo Palmier; Totola, Antônio Helvécio; Vieira, Leda Quércia; Sobrinho, Antônio Paulino Ribeiro

2012-04-01

Lymphocytes, among many cells, express different sets of cytokines, chemokines, and receptors, which are considered important mediators of periapical immune response to infection. The aim of this study was to evaluate the mRNA expression of CD4(+)CD28(+) and CD8(+) T genes and the gene expression of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-17A, IL-10, CCL2/MCP-1, CCL4, CCL5, CXCR4, CCR5, and receptor activator for nuclear factor kappa B ligand (RANKL) in periapical interstitial fluid from human root canal infections. The samples were collected immediately after root canal cleaning and 7 days later (restrained root canal bacterial load) to characterize those gene expressions. Real-time polymerase chain reaction demonstrated significantly higher levels of CD4(+)CD28(+) and CD8(+) T-cell markers in the former root canal condition and an increase of IL-10 and CXCR4, followed by a decrease of proinflammatory cytokines such as RANKL, interferon-γ, IL-1β, and CCL5. Analyses of T-lymphocyte and cytokine expression in periapical area were able to show that distinct root canal conditions might play regulatory roles in controlling local immune/inflammatory processes. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

In Vivo Efficacy of Latex from Calotropis procera in Ameliorating Fever-Biochemical Characteristics and Plausible Mechanism.

PubMed

Kumar, Vijay L; Guruprasad, B; Fatmi, Syed Meraj A; Chaudhary, Priyanka; Alencar, Nylane Maria Nunes; Lima-Filho, José Vitor Moreira; Ramos, Márcio Viana

2017-07-01

Calotropis procera latex fractions possessing anti-inflammatory property were characterized for their biochemical properties, compared for their efficacy in ameliorating fever in rats and their mechanism of action was elucidated. Aqueous fraction and methanol extract (AqDL and MeDL) were derived from the dried latex (DL) and proteins were separated from the fresh latex (LP). Polyacrylamide gel electrophoresis carried out under denaturing conditions showed the presence of proteins with some similarity in LP and AqDL and both of these fractions exhibited proteinase activity by gelatin zymography. A further analysis revealed that only the LP fraction possesses cysteine proteinase activity. Oral administration of both AqDL and MeDL produced a dose-dependent reduction in body temperature in rats where fever was induced by yeast and their effect was comparable to that of standard drug paracetamol while intravenous administration of LP was not so effective. Both AqDL and MeDL produced a significant reduction in the levels of TNF-α, PGE 2 , and immunoreactivity of COX-2 in the hypothalamus as compared to yeast control group. This study shows that both AqDL and MeDL, the orally effective anti-inflammatory fractions of latex, have therapeutic potential in treating various febrile conditions.

Thrombocytosis: a retrospective study of 165 dogs.

PubMed

Neel, Jennifer A; Snyder, Laura; Grindem, Carol B

2012-06-01

Thrombocytosis has been associated with various conditions, including inflammation, neoplasia, iron deficiency, splenectomy, and drug administration. The aim of this study was to characterize diseases and conditions associated with thrombocytosis in dogs. In this retrospective study, dogs with thrombocytosis (platelet count > 600 × 10(3) /μL) and complete medical records during a 1-year period were included, and breed, sex, age, CBC results, alkaline phosphatase and gamma-glutamyltransferase activities in some dogs, administration of glucocorticoids or vincristine, and primary diagnosis were evaluated. Thrombocytosis was found in 240 of 5342 dogs (4.6%), and 165 (3.1%) met inclusion criteria. Thrombocytosis was secondary in all dogs, and underlying diseases and conditions (n,%) were neoplasia (56, 33.9%), inflammation (55, 33.3%), miscellaneous disorders (26, 15.8%), neoplasia plus a second disease (13, 7.9%), endocrine diseases (8, 4.8%), and multiple diseases (7, 4.2%). In dogs with neoplasia, carcinomas (24) and round cell neoplasms (20), especially lymphoma and mast cell tumor, were the most frequent tumors. Inflammatory disorders consisted of immune-mediated disorders (11), neurologic diseases (8), infectious diseases (6), allergic disease (5), orthopedic diseases (4), gastrointestinal diseases (4), and miscellaneous conditions (17). Of the 165 dogs, 73 (44.2%) had received glucocorticoids (55) or vincristine (18) Marked (850-969 × 10(3) platelets/μL) or extreme ( ≥ 970 × 10(3) platelets/μL) thrombocytosis occurred in 24 (14.5%) dogs; 12 (50.0%) had neoplasia. Thromboembolism occurred in 13 (7.9%) dogs. Thrombocytosis in dogs occurred most frequently secondary to neoplastic and inflammatory diseases and was commonly associated with glucocorticoid and vincristine administration. Thromboembolic complications occurred in a small number of patients. Marked or extreme thrombocytosis was more likely to occur with neoplasia than with other conditions. © 2012 American Society for Veterinary Clinical Pathology.

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

PubMed

Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

2016-11-15

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterization of plasma labile heme in hemolytic conditions

PubMed Central

Gouveia, Zélia; Carlos, Ana R.; Yuan, Xiaojing; Aires-da-Silva, Frederico; Stocker, Roland; Maghzal, Ghassan J.; Leal, Sónia S.; Gomes, Cláudio M.; Todorovic, Smilja; Iranzo, Olga; Ramos, Susana; Santos, Ana C.; Hamza, Iqbal; Gonçalves, João; Soares, Miguel P.

2018-01-01

Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. This produces metabolically active heme that is exchangeable between acceptor proteins, macromolecules and low molecular weight ligands, termed here labile heme. As it accumulates in plasma labile heme acts in a pro-oxidant manner and regulates cellular metabolism while exerting pro-inflammatory and cytotoxic effects that foster the pathogenesis of hemolytic diseases. Here, we developed and characterized a panel of heme-specific single domain antibodies (sdAbs) that together with a cellular-based heme reporter assay, allow for quantification and characterization of labile heme in plasma during hemolytic conditions. Using these approaches, we demonstrate that when generated during hemolytic conditions labile heme is bound to plasma molecules with an affinity higher than 10−7 m and that 2–8% (∼ 2–5 μm) of the total amount of heme detected in plasma can be internalized by bystander cells, termed here bioavailable heme. Acute, but not chronic, hemolysis is associated with transient reduction of plasma heme-binding capacity, that is, the ability of plasma molecules to bind labile heme with an affinity higher than 10−7 m. The heme-specific sdAbs neutralize the pro-oxidant activity of soluble heme in vitro, suggesting that these maybe used to counter the pathologic effects of labile heme during hemolytic conditions. Finally, we show that heme-specific sdAbs can be used to visualize cellular heme. In conclusion, we describe a panel of heme-specific sdAbs that when used with other approaches provide novel insights to the pathophysiology of heme. PMID:28783254

Infection, inflammation and exercise in cystic fibrosis

PubMed Central

2013-01-01

Regular exercise is positively associated with health. It has also been suggested to exert anti-inflammatory effects. In healthy subjects, a single exercise session results in immune cell activation, which is characterized by production of immune modulatory peptides (e.g. IL-6, IL-8), a leukocytosis and enhanced immune cell functions. Upon cessation of exercise, immune activation is followed by a tolerizing phase, characterized by a reduced responsiveness of immune cells. Regular exercise of moderate intensity and duration has been shown to exert anti-inflammatory effects and is associated with a reduced disease incidence and viral infection susceptibility. Specific exercise programs may therefore be used to modify the course of chronic inflammatory and infectious diseases such as cystic fibrosis (CF). Patients with CF suffer from severe and chronic pulmonary infections and inflammation, leading to obstructive and restrictive pulmonary disease, exercise intolerance and muscle cachexia. Inflammation is characterized by a hyper-inflammatory phenotype. Patients are encouraged to engage in exercise programs to maintain physical fitness, quality of life, pulmonary function and health. In this review, we present an overview of available literature describing the association between regular exercise, inflammation and infection susceptibility and discuss the implications of these observations for prevention and treatment of inflammation and infection susceptibility in patients with CF. PMID:23497303

Role of IRE1α/XBP-1 in Cystic Fibrosis Airway Inflammation

PubMed Central

Ribeiro, Carla M. P.; Lubamba, Bob A.

2017-01-01

Cystic fibrosis (CF) pulmonary disease is characterized by chronic airway infection and inflammation. The infectious and inflamed CF airway environment impacts on the innate defense of airway epithelia and airway macrophages. The CF airway milieu induces an adaptation in these cells characterized by increased basal inflammation and a robust inflammatory response to inflammatory mediators. Recent studies have indicated that these responses depend on activation of the unfolded protein response (UPR). This review discusses the contribution of airway epithelia and airway macrophages to CF airway inflammatory responses and specifically highlights the functional importance of the UPR pathway mediated by IRE1/XBP-1 in these processes. These findings suggest that targeting the IRE1/XBP-1 UPR pathway may be a therapeutic strategy for CF airway disease. PMID:28075361

Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyflavones from Ageratum conyzoides.

PubMed

Faqueti, Larissa G; Brieudes, Vincent; Halabalaki, Maria; Skaltsounis, Alexios L; Nascimento, Leandro F; Barros, Wellinghton M; Santos, Adair R S; Biavatti, Maique W

2016-12-24

Ageratum conyzoides L. is a plant widely used in traditional medicine in tropical and subtropical regions of the world due to its anti-inflammatory, antinociceptive and antibacterial properties. To characterize the standardized extract of polymethoxyflavones (SEPAc) from the plant and evaluate its antinociceptive and anti-inflammatory effects. The SEPAc purified from the ethanol extract of the plant leaves was characterized by high resolution mass spectrometry and the methoxyflavones were quantified by a validated UPLC-PDA method. The antinociceptive and anti-inflammatory activities of the SEPAc were evaluated after oral administration on the acute nocifensive behavior of mice induced by formalin, prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukin-1beta (IL-1β)) and tumor necrosis factor-alpha (TNF-α) in mice. Qualitative analyses revealed the presence of seven methoxyflavones in the SEPAc, also a simple UPLC-PDA method was developed and validated for the quantification of 5,6,7,3',4',5'-hexametoxyflavone; nobiletin; 5'-methoxynobiletin and eupalestin, major compounds in the extract. The SEPAc exhibited antinociceptive and anti-inflammatory activities in both formalin phases, with significant inhibition of the paw edema formation and significant reduction of the nocifensive response induced by an intraplantar injection of PGE2 and intrathecal injection of interleukin-1β. The SEPAc exhibited significant antinociceptive and anti-inflammatory effects. These results provided scientific suggestion of its potential as a source of new medicines to treat inflammatory diseases, such rheumatoid arthritis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anti-inflammatory effects of EMD in the presence of biomechanical loading and interleukin-1β in vitro.

PubMed

Nokhbehsaim, Marjan; Deschner, Birgit; Winter, Jochen; Bourauel, Christoph; Jäger, Andreas; Jepsen, Søren; Deschner, James

2012-02-01

Enamel matrix derivative (EMD) used to promote periodontal regeneration has been shown to exert anti-inflammatory effects. This in vitro study was performed to investigate if the anti-inflammatory actions of EMD are modulated by the local cellular environment, such as inflammation or occlusal, i.e., biomechanical, loading. Human periodontal ligament cells were seeded on BioFlex plates and incubated with EMD under normal, inflammatory, and biomechanical loading conditions for 1 and 6 days. In order to mimic inflammatory and biomechanical loading conditions in vitro, cells were stimulated with interleukin (IL)-1β and exposed to dynamic tensile strain, respectively. The gene expression of IL-1β, IL-1 receptor antagonist (IL-1RN), IL-6, IL-8, IL-10, and cyclooxygenase (COX)-2 was analyzed by real-time RT-PCR and the IL-6 protein synthesis by enzyme-linked immunoassay. For statistical analysis, Student's t test, ANOVA, and post-hoc comparison tests were applied (p < 0.05). EMD downregulated significantly the expression of IL-1β and COX-2 at 1 day and of IL-6, IL-8, and COX-2 at 6 days in normal condition. In an inflammatory environment, the anti-inflammatory actions of EMD were significantly enhanced at 6 days. In the presence of low biomechanical loading, EMD caused a downregulation of IL-1β and IL-8, whereas high biomechanical loading significantly abrogated the anti-inflammatory effects of EMD at both days. Neither IL-1RN nor IL-10 was upregulated by EMD. These data suggest that high occlusal forces may abrogate anti-inflammatory effects of EMD and should, therefore, be avoided immediately after the application of EMD to achieve best healing results.

Nutraceuticals in rodent models as potential treatments for human Inflammatory Bowel Disease.

PubMed

Ghattamaneni, Naga K R; Panchal, Sunil K; Brown, Lindsay

2018-04-20

Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of all or part of the digestive tract. Nutraceuticals include bioactive compounds such as polyphenols with anti-inflammatory activities, thus these products have the potential to treat chronic inflammatory diseases. We have emphasized the role of nutraceuticals in ameliorating the symptoms of IBD in rodent models of human IBD through modulation of key pathogenic mechanisms including dysbiosis, oxidative stress, increased inflammatory cytokines, immune system dysregulation, and inflammatory cell signaling pathways. Nutraceuticals have an important role in IBD patients as a preventive approach to extend remission phases and as a therapeutic intervention to suppress active IBD. Further clinical trials on nutraceuticals with positive results in rodent models are warranted. Copyright © 2018. Published by Elsevier Ltd.

Evaluation of a nanotechnology-based approach to induce gene-expression in human THP-1 macrophages under inflammatory conditions.

PubMed

Bernal, Laura; Alvarado-Vázquez, Abigail; Ferreira, David Wilson; Paige, Candler A; Ulecia-Morón, Cristina; Hill, Bailey; Caesar, Marina; Romero-Sandoval, E Alfonso

2017-02-01

Macrophages orchestrate the initiation and resolution of inflammation by producing pro- and anti-inflammatory products. An imbalance in these mediators may originate from a deficient or excessive immune response. Therefore, macrophages are valid therapeutic targets to restore homeostasis under inflammatory conditions. We hypothesize that a specific mannosylated nanoparticle effectively induces gene expression in human macrophages under inflammatory conditions without undesirable immunogenic responses. THP-1 macrophages were challenged with lipopolysaccharide (LPS, 5μg/mL). Polyethylenimine (PEI) nanoparticles grafted with a mannose receptor ligand (Man-PEI) were used as a gene delivery method. Nanoparticle toxicity, Man-PEI cellular uptake rate and gene induction efficiency (GFP, CD14 or CD68) were studied. Potential immunogenic responses were evaluated by measuring the production of tumor necrosis factor-alpha (TNF-α), Interleukin (IL)-6 and IL-10. Man-PEI did not produce cytotoxicity, and it was effectively up-taken by THP-1 macrophages (69%). This approach produced a significant expression of GFP (mRNA and protein), CD14 and CD68 (mRNA), and transiently and mildly reduced IL-6 and IL-10 levels in LPS-challenged macrophages. Our results indicate that Man-PEI is suitable for inducing an efficient gene overexpression in human macrophages under inflammatory conditions with limited immunogenic responses. Our promising results set the foundation to test this technology to induce functional anti-inflammatory genes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Adipocytes properties and crosstalk with immune system in obesity-related inflammation.

PubMed

Maurizi, Giulia; Della Guardia, Lucio; Maurizi, Angela; Poloni, Antonella

2018-01-01

Obesity is a condition likely associated with several dysmetabolic conditions or worsening of cardiovascular and other chronic disturbances. A key role in this mechanism seem to be played by the onset of low-grade systemic inflammation, highlighting the importance of the interplay between adipocytes and immune system cells. Adipocytes express a complex and highly adaptive biological profile being capable to selectively activate different metabolic pathways in order to respond to environmental stimuli. It has been demonstrated how adipocytes, under appropriate stimulation, can easily differentiate and de-differentiate thereby converting themselves into different phenotypes according to metabolic necessities. Although underlying mechanisms are not fully understood, growing in adipocyte size and the inability of storing triglycerides under overfeeding conditions seem to be crucial for the switching to a dysfunctional metabolic profile, which is characterized by inflammatory and apoptotic pathways activation, and by the shifting to pro-inflammatory adipokines secretion. In obesity, changes in adipokines secretion along with adipocyte deregulation and fatty acids release into circulation contribute to maintain immune cells activation as well as their infiltration into regulatory organs. Over the well-established role of macrophages, recent findings suggest the involvement of new classes of immune cells such as T regulatory lymphocytes and neutrophils in the development inflammation and multi systemic worsening. Deeply understanding the pathways of adipocyte regulation and the de-differentiation process could be extremely useful for developing novel strategies aimed at curbing obesity-related inflammation and related metabolic disorders. © 2017 Wiley Periodicals, Inc.

Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease.

PubMed

Zhang, Liping; Rajan, Vik; Lin, Eugene; Hu, Zhaoyong; Han, H Q; Zhou, Xiaolan; Song, Yanping; Min, Hosung; Wang, Xiaonan; Du, Jie; Mitch, William E

2011-05-01

Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC(50) ∼1.2 nM) reversed the loss of body weight (≈5-7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38 ± 1.29%; P<0.05), increased protein synthesis in extensor digitorum longus muscles (13.21 ± 1.09%; P<0.05), markedly enhanced satellite cell function, and improved IGF-1 intracellular signaling. In cultured muscle cells, TNF-α increased myostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.

Condition-specific role of colonic inflammatory molecules in persistent functional colorectal hypersensitivity in the mouse

PubMed Central

La, Jun-Ho; Gebhart, G. F.

2014-01-01

Background A low-level inflammation has been hypothesized to mediate visceral hypersensitivity in functional bowel disorders that persist after or even in the absence of gut inflammation. We aimed to test the efficacy of a steroidal anti-inflammatory treatment, and identify local inflammatory molecules mediating post- and non-inflammatory colorectal hypersensitivity using two mouse models. Methods Visceromotor responses to colorectal distension were quantified as a measure of colorectal sensitivity. On day 1, mice received intracolonic saline (control), trinitrobenzenesulfonic acid (post-inflammatory on day 15), or acidified hypertonic saline (non-inflammatory). Colorectal sensitivity before (day 10) and after (day 15) four-day dexamethasone treatment was compared, and colonic gene expression of inflammatory molecules was quantified. Results Dexamethasone effectively inhibited gene expression of inflammatory molecules such as interleukin (IL)-1β and mast cell protease-1 in the colon, but did not attenuate colorectal hypersensitivity in either model. Gene expression of inflammatory molecules in the colon did not differ between control and the non-inflammatory model, but the post-inflammatory model showed increased IL-10 and tight junction protein 2, and decreased IL-6, transforming growth factor (TGF)-β, a precursor of β-endorphin, occludin, and mucin 2. While no common molecule explained colorectal hypersensitivity in these models, hypersensitivity was positively correlated with TGF-β2 mRNA in control, and with IL-1β, inhibin βA and prostaglandin E2 synthase in the dexamethasone-treated post-inflammatory model. In the non-inflammatory model, cyclooxygenase-2 mRNA was negatively correlated with colorectal sensitivity. Conclusion These results suggest that persistent functional colorectal hypersensitivity is mediated by condition-specific mediators whose gene expression in the colon is not inevitably sensitive to steroidal anti-inflammatory treatment. PMID:25307695

Tonic regulation of vascular permeability

PubMed Central

Curry, Fitz-Roy E.; Adamson, Roger H.

2014-01-01

Our major theme is that the layered structure of the endothelial barrier requires continuous activation of signaling pathways regulated by S1P and intracellular cAMP. These pathways modulate the adherens junction, continuity of tight junction strands, and the balance of synthesis and degradation of glycocalyx components. We evaluate recent evidence that baseline permeability is maintained by constant activity of mechanisms involving the small GTPases Rap1 and Rac1. In the basal state, the barrier is compromised when activities of the small GTPases are reduced by low S1P supply or delivery. With inflammatory stimulus, increased permeability can be understood in part as the action of signaling to reduce Rap1 and Rac1 activation. With the hypothesis that microvessel permeability and selectivity under both normal and inflammatory conditions are regulated by mechanisms that are continuously active it follows that when S1P or intracellular cAMP are elevated at the time of inflammatory stimulus, they can buffer changes induced by inflammatory agents and maintain normal barrier stability. When endothelium is exposed to inflammatory conditions and subsequently exposed to elevated S1P or intracellular cAMP, the same processes restore the functional barrier by first reestablishing the adherens junction, then modulating tight junctions and glycocalyx. In more extreme inflammatory conditions, loss of the inhibitory actions of Rac1 dependent mechanisms may promote expression of more inflammatory endothelial phenotypes by contributing to the up-regulation of RhoA dependent contractile mechanisms and the sustained loss of surface glycocalyx allowing access of inflammatory cells to the endothelium. PMID:23374222

Targeting inflammation in the treatment of type 2 diabetes: time to start.

PubMed

Donath, Marc Y

2014-06-01

The role of inflammation in the pathogenesis of type 2 diabetes and associated complications is now well established. Several conditions that are driven by inflammatory processes are also associated with diabetes, including rheumatoid arthritis, gout, psoriasis and Crohn's disease, and various anti-inflammatory drugs have been approved or are in late stages of development for the treatment of these conditions. This review discusses the rationale for the use of some of these anti-inflammatory treatments in patients with diabetes and what we could expect from their use. Future immunomodulatory treatments may not target a specific disease, but could instead act on a dysfunctional pathway that causes several conditions associated with the metabolic syndrome.

DIESEL EXHAUST PARTICULATE (DEP)-INDUCED ACTIV ATION OF STAT3 REQUIRES ACTIVITIES OF EGFR AND SRC IN AIRWAY EPITHELIAL CELLS

EPA Science Inventory

In vivo exposure to diesel exhaust particles (DEP) elicits acute inflammatory responses in the lung characterized by inflammatory cell influx and elevated expression of mediators such as cytokines, and chemokines. Signal transducers and activators of transcription (STAT) protein...

Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1.

PubMed

Gan, Zhen-Shun; Wang, Qian-Qian; Li, Jia-Hui; Wang, Xu-Liang; Wang, Yi-Zhen; Du, Hua-Hua

2017-01-01

Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN- γ . The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1 β , TNF- α , and iNOS produced by IFN- γ -polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer

PubMed Central

Kang, Rui; Xie, Yangchun; Zhang, Qiuhong; Hou, Wen; Jiang, Qingping; Zhu, Shan; Liu, Jinbao; Zeng, Dexing; Wang, Haichao; Bartlett, David L; Billiar, Timothy R; Zeh, Herbert J; Lotze, Michael T; Tang, Daolin

2017-01-01

Pancreatic ductal adenocarcinoma (PDAC) driven by oncogenic K-Ras remains among the most lethal human cancers despite recent advances in modern medicine. The pathogenesis of PDAC is partly attributable to intrinsic chromosome instability and extrinsic inflammation activation. However, the molecular link between these two events in pancreatic tumorigenesis has not yet been fully established. Here, we show that intracellular high mobility group box 1 (HMGB1) remarkably suppresses oncogenic K-Ras-driven pancreatic tumorigenesis by inhibiting chromosome instability-mediated pro-inflammatory nucleosome release. Conditional genetic ablation of either single or both alleles of HMGB1 in the pancreas renders mice extremely sensitive to oncogenic K-Ras-driven initiation of precursor lesions at birth, including pancreatic intraepithelial neoplasms, intraductal papillary mucinous neoplasms, and mucinous cystic neoplasms. Loss of HMGB1 in the pancreas is associated with oxidative DNA damage and chromosomal instability characterized by chromosome rearrangements and telomere abnormalities. These lead to inflammatory nucleosome release and propagate K-Ras-driven pancreatic tumorigenesis. Extracellular nucleosomes promote interleukin 6 (IL-6) secretion by infiltrating macrophages/neutrophils and enhance oncogenic K-Ras signaling activation in pancreatic lesions. Neutralizing antibodies to IL-6 or histone H3 or knockout of the receptor for advanced glycation end products all limit K-Ras signaling activation, prevent cancer development and metastasis/invasion, and prolong animal survival in Pdx1-Cre;K-RasG12D/+;Hmgb1−/− mice. Pharmacological inhibition of HMGB1 loss by glycyrrhizin limits oncogenic K-Ras-driven tumorigenesis in mice under inflammatory conditions. Diminished nuclear and total cellular expression of HMGB1 in PDAC patients correlates with poor overall survival, supporting intracellular HMGB1 as a novel tumor suppressor with prognostic and therapeutic relevance in PDAC. PMID:28374746

Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma.

PubMed

Smolensky, Michael H; Lemmer, Bjoern; Reinberg, Alain E

2007-08-31

Study of the chronobiology of allergic rhinitis (AR) and bronchial asthma (BA) and the chronopharmacology and chronotherapy of the medications used in their treatment began five decades ago. AR is an inflammatory disease of the upper airway tissue with hypersensitivity to specific environmental antigens, resulting in further local inflammation, vasomotor changes, and mucus hypersecretion. Symptoms include sneezing, nasal congestion, and runny and itchy nose. Approximately 25% of children and 40% of adults in USA are affected by AR during one or more seasons of the year. The manifestation and severity of AR symptoms exhibit prominent 24-h variation; in most persons they are worse overnight or early in the morning and often comprise nighttime sleep, resulting in poor daytime quality of life, compromised school and work performance, and irritability and moodiness. BA is also an inflammatory medical condition of the lower airways characterized by hypersensitivity to specific environmental antigens, resulting in greater local inflammation as well as bronchoconstriction, vasomotor change, and mucus hypersecretion. In USA an estimated 6.5 million children and 15.7 million adults have BA. The onset and worsening of BA are signaled by chest wheeze and/or croupy cough and difficult and labored breathing. Like AR, BA is primarily a nighttime medical condition. AR is treated with H1-antagonist, decongestant, and anti-inflammatory (glucocorticoid and leukotriene receptor antagonist and modifier) medications. Only H1-antagonist AR medications have been studied for their chronopharmacology and potential chronotherapy. BA is treated with some of the same medications and also theophylline and beta2-agonists. The chronopharmacology and chronotherapy of many classes of BA medications have been explored. This article reviews the rather extensive knowledge of the chronobiology of AR and BA and the chronopharmacology and chronotherapy of the various medications used in their treatment.

Normal adiponectin levels despite abnormal glucose tolerance (or diabetes) and inflammation in adult patients with cystic fibrosis.

PubMed

Hammana, I; Malet, A; Costa, M; Brochiero, E; Berthiaume, Y; Potvin, S; Chiasson, J-L; Coderre, L; Rabasa-Lhoret, R

2007-06-01

Circulating adiponectin levels are negatively associated with glucose intolerance, inflammation and central adiposity. Since these conditions are common in cystic fibrosis (CF), we examined whether adiponectin values are altered in these patients. To determine if CF patients have altered adiponectin levels and if these levels correlate with glucose tolerance categories (normal, impaired glucose tolerance (IGT) and cystic fibrosis-related diabetes (CFRD)), insulin resistance or inflammatory markers such as fibrinogen and C-reactive protein (CRP). Oral glucose tolerance tests (OGTTs) were performed and adiponectin levels were measured in 90 CF patients not known to be diabetic and 15 healthy controls matched for age, sex and body mass index (BMI). Inflammatory markers, serum albumin concentrations and the clinical status of CF patients (i.e. pulmonary function) were also examined. CF pathology was characterized by a high prevalence (43.5%) of glucose tolerance abnormalities: 26.5% of IGT and 17.0% of newly diagnosed CFRD. CF patients also presented systemic inflammation as revealed by a significant increase of fibrinogen (P=0.029) in all patients and higher CRP levels in CFRD patients compared to the controls (P<0.05). On the other hand, CF and control subjects had similar albumin serum concentration. While CF patients and controls had similar serum adiponectin values, women had significantly higher hormone levels than men (P<0.001). Adiponectin levels did not correlate with glucose tolerance, inflammatory markers or insulin resistance. On the other hand, they correlated positively with both total and HDL-cholesterol (P<0.001). CF patients did not show any alterations in adiponectin levels despite insulin resistance, glucose intolerance and sub clinical chronic inflammation. Thus, CF appears to be one of the rare conditions in which discordance between adiponectin values and insulin resistance or inflammation is evident.

Giant lymphedema of the penis and scrotum: a case report.

PubMed

Vives, Franklin; García-Perdomo, Herney Andrés; Ocampo-Flórez, Ginna Marcela

2016-01-01

Lymphedema of the penis and scrotum is a rare entity characterized by enlargement of the skin and subcutaneous tissue of the genital region due to lymphatic drainage impairment. This clinical condition is more frequent in tropical countries due to a higher incidence of filariasis, which, in turn, is the main etiology. We describe the case of a 33-year-old man with large lymphedema of the scrotum and penis due to an acute and chronic inflammatory process, foreign body granuloma, and marked hyalinization. Four consecutive surgical interventions were necessary to remove the great part of the affected tissue, which enabled satisfactory results and improved the patient's quality of life.

Toll-like receptor-associated keratitis and strategies for its management.

PubMed

Kaur, Amandeep; Kumar, Vijay; Singh, Simranjeet; Singh, Joginder; Upadhyay, Niraj; Datta, Shivika; Singla, Sourav; Kumar, Virender

2015-10-01

Keratitis is an inflammatory condition, characterized by involvement of corneal tissues. Most recurrent challenge of keratitis is infection. Bacteria, virus, fungus and parasitic organism have potential to cause infection. TLR are an important class of protein which has a major role in innate immune response to combat with pathogens. In last past years, extensive research efforts have provided considerable abundance information regarding the role of TLR in various types of keratitis. This paper focuses to review the recent literature illustrating amoebic, bacterial, fungal and viral keratitis associated with Toll-like receptor molecules and summarize existing thoughts on pathogenesis and treatment besides future probabilities for prevention against TLR-associated keratitis.

Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity and Special Mechanism*

PubMed Central

Wei, Lin; Gao, Jiuxiang; Zhang, Shumin; Wu, Sijin; Xie, Zeping; Ling, Guiying; Kuang, Yi-Qun; Yang, Yongliang; Yu, Haining; Wang, Yipeng

2015-01-01

Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized previously. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids, and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic α-helical conformation in bacterial membrane-mimetic solutions. It possesses potent broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells. The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. In addition, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Hc-CATH directly binds with LPS to neutralize its toxicity, and it also binds to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake discovered to have both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics. PMID:26013823

Dyadic confirmatory factor analysis of the inflammatory bowel disease family responsibility questionnaire.

PubMed

Greenley, Rachel Neff; Reed-Knight, Bonney; Blount, Ronald L; Wilson, Helen W

2013-09-01

Evaluate the factor structure of youth and maternal involvement ratings on the Inflammatory Bowel Disease Family Responsibility Questionnaire, a measure of family allocation of condition management responsibilities in pediatric inflammatory bowel disease. Participants included 251 youth aged 11-18 years with inflammatory bowel disease and their mothers. Item-level descriptive analyses, subscale internal consistency estimates, and confirmatory factor analyses of youth and maternal involvement were conducted using a dyadic data-analytic approach. Results supported the validity of 4 conceptually derived subscales including general health maintenance, social aspects, condition management tasks, and nutrition domains. Additionally, results indicated adequate support for the factor structure of a 21-item youth involvement measure and strong support for a 16-item maternal involvement measure. Additional empirical support for the validity of the Inflammatory Bowel Disease Family Responsibility Questionnaire was provided. Future research to replicate current findings and to examine the measure's clinical utility is warranted.

Colonic macrophage polarization in homeostasis, inflammation, and cancer

PubMed Central

Appleyard, Caroline B.

2016-01-01

Our review focuses on the colonic macrophage, a monocyte-derived, tissue-resident macrophage, and the role it plays in health and disease, specifically in inflammatory conditions such as inflammatory bowel disease and cancer of the colon and rectum. We give special emphasis to macrophage polarization, or phenotype, in these different states. We focus on macrophages because they are one of the most numerous leukocytes in the colon, and because they normally contribute to homeostasis through an anti-inflammatory phenotype. However, in conditions such as inflammatory bowel disease, proinflammatory macrophages are increased in the colon and have been linked to disease severity and progression. In colorectal cancer, tumor cells may employ anti-inflammatory macrophages to promote tumor growth and dissemination, whereas proinflammatory macrophages may antagonize tumor growth. Given the key roles that this cell type plays in homeostasis, inflammation, and cancer, the colonic macrophage is an intriguing therapeutic target. As such, potential macrophage-targeting strategies are discussed. PMID:27229123

Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence.

PubMed

Agossa, K; Dendooven, A; Dubuquoy, L; Gower-Rousseau, C; Delcourt-Debruyne, E; Capron, M

2017-06-01

Inflammatory bowel disease and periodontitis are both described as a disproportionate mucosal inflammatory response to a microbial environment in susceptible patients. Moreover, these two conditions share major environmental and lifestyle-related risk factors. Despite this intriguing pathogenic parallel, large-scale studies and basic research have only recently considered periodontal outcomes as relevant data. There are mounting and consistent arguments, from recent epidemiologic studies and animal models, that these two conditions might be related. This article is a comprehensive and critical up-to-date review of the current evidence and future prospects in understanding the biologic and epidemiologic relationships between periodontal status and inflammatory bowel disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hypertrophic Osteoarthropathy: Clinical and Imaging Features.

PubMed

Yap, Felix Y; Skalski, Matthew R; Patel, Dakshesh B; Schein, Aaron J; White, Eric A; Tomasian, Anderanik; Masih, Sulabha; Matcuk, George R

2017-01-01

Hypertrophic osteoarthropathy (HOA) is a medical condition characterized by abnormal proliferation of skin and periosteal tissues involving the extremities and characterized by three clinical features: digital clubbing (also termed Hippocratic fingers), periostosis of tubular bones, and synovial effusions. HOA can be a primary entity, known as pachydermoperiostosis, or can be secondary to extraskeletal conditions, with different prognoses and management implications for each. There is a high association between secondary HOA and malignancy, especially non-small cell lung cancer. In such cases, it can be considered a form of paraneoplastic syndrome. The most prevalent secondary causes of HOA are pulmonary in origin, which is why this condition was formerly referred to as hypertrophic pulmonary osteoarthropathy. HOA can also be associated with pleural, mediastinal, and cardiovascular causes, as well as extrathoracic conditions such as gastrointestinal tumors and infections, cirrhosis, and inflammatory bowel disease. Although the skeletal manifestations of HOA are most commonly detected with radiography, abnormalities can also be identified with other modalities such as computed tomography, magnetic resonance imaging, and bone scintigraphy. The authors summarize the pathogenesis, classification, causes, and symptoms and signs of HOA, including the genetics underlying the primary form (pachydermoperiostosis); describe key findings of HOA found at various imaging modalities, with examples of underlying causative conditions; and discuss features differentiating HOA from other causes of multifocal periostitis, such as thyroid acropachy, hypervitaminosis A, chronic venous insufficiency, voriconazole-induced periostitis, progressive diaphyseal dysplasia, and neoplastic causes such as lymphoma. © RSNA, 2016.

Cyclooxygenase inhibitory natural products: current status.

PubMed

Jachak, Sanjay M

2006-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are of huge therapeutic benefit in the treatment of rheumatoid arthritis and various types of inflammatory conditions. The target for these drugs is cyclooxygenase (COX), a rate-limiting enzyme involved in the conversion of arachidonic acid into inflammatory prostaglandins. COX-2 selective inhibitors are believed to have the same anti-inflammatory, anti-pyretic and analgesic activities as that of nonselective inhibitor NSAIDs with little or none of the gastrointestinal side effects. Thus, in the last 6-7 years several selective COX-2 inhibitors including coxibs were discovered and introduced into clinic. Recent reports evidence that selective COX-2 inhibitor such as rofecoxib, can lead to thrombotic cardiovascular events through inhibition of prostacyclin formation in the infracted heart. This has resulted in withdrawal of rofecoxib from the clinic in September 2004. Moreover, the COX-2/COX-1 selectivity ratio is vital in the design of COX-2 inhibitory drugs, as it is clear from rofecoxib, which is more than 50-fold COX-2 selective. After looking at all above mentioned facts, natural product-based compounds seem better as these compounds are generally supposed to be devoid of severe side effects. The literature indicates that natural product-based compounds are mainly COX-1 selective. Through minor semi-synthetic changes in the structures, their selectivity towards COX-2 can be increased. The present review article addresses natural product COX inhibitors of plant and marine origin, reported during last ten years and their advantages, possible leads for further development and current status. In addition we describe our experience in the characterization, design and synthesis of potential natural COX inhibitors.

Sex-specific control of CNS autoimmunity by p38 MAPK signaling in myeloid cells

PubMed Central

Krementsov, Dimitry N.; Noubade, Rajkumar; Dragon, Julie A.; Otsu, Kinya; Rincon, Mercedes; Teuscher, Cory

2013-01-01

Objective Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38α signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38α in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38α-controlled transcripts comprising female- and male-specific gene modules, with greater p38α dependence of pro-inflammatory gene expression in females. Interpretation Our findings demonstrate a key role for p38α in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS. PMID:24027119

Detection of DSS-induced gastrointestinal mucositis in mice by non-invasive optical near-infrared (NIR) imaging of cathepsin activity.

PubMed

Finnberg, Niklas K; Liu, Yvette; El-Deiry, Wafik S

2013-08-01

Approximately 1.4 million people of the US population suffer from Inflammatory Bowel Disease (IBD) of which the most common conditions are ulcerative colitis (UC) and Crohn disease (CD). Colonoscopy and small bowel follow through are considered the current gold standard in diagnosing IBD. However, improved imaging and increased diagnostic sensitivity could be beneficial. Optical molecular imaging has the potential to become a powerful and practical tool for early detection, image-guided biopsy, and surgery in diagnosing and treating patients with IBD. Here we used a well characterized chemical model to initiate experimental IBD in mice by feeding with dextran sulfate sodium (DSS) containing drinking water in an attempt to investigate the utility of non-invasive infrared (NIR) optical imaging in the detection gastrointestinal (GI) injury. We employed a "smart probe" (ProSense680) cleaved and fluorescently activated in the NIR-spectrum by various forms of secreted cathepsins. This probe has previously been shown to serve as a biomarker for the homing of inflammatory cells to injury. Our investigation suggests that NIR optical imaging can detect cathepsin-dependent probe cleavage non-invasively in animals with DSS-induced IBD. Increased tissue probe-retention and fluorescence was associated with increased infiltration of inflammatory cells, epithelial atrophy and sterilization of the mucosa. Furthermore, using NIR-imaging ex vivo we were able to document regional "hot spots" of inflammatory damage to the large intestine suggesting this method potentially could be coupled with colonoscopy investigation to aid in the sampling and the diagnostics of IBD.

Using corticosteroids to reshape the gut microbiome: implications for inflammatory bowel diseases.

PubMed

Huang, Edmond Y; Inoue, Takuya; Leone, Vanessa A; Dalal, Sushila; Touw, Ketrija; Wang, Yunwei; Musch, Mark W; Theriault, Betty; Higuchi, Kazuhide; Donovan, Sharon; Gilbert, Jack; Chang, Eugene B

2015-05-01

Commensal gut microbiota play an important role in regulating metabolic and inflammatory conditions. Reshaping intestinal microbiota through pharmacologic means may be a viable treatment option. We sought to delineate the functional characteristics of glucocorticoid-mediated alterations on gut microbiota and their subsequent repercussions on host mucin regulation and colonic inflammation. Adult male C57Bl/6 mice, germ-free, Muc2-heterozygote (±), or Muc2-knockout (-/-) were injected with dexamethasone, a synthetic glucocorticoid, for 4 weeks. Fecal samples were collected for gut microbiota analysis through 16S rRNA terminal restriction fragment length polymorphism and amplicon sequencing. Intestinal mucosa was collected for mucin gene expression studies. Germ-free mice were conventionalized with gut microbes from treated and nontreated groups to determine their functional capacities in recipient hosts. Exposure to dexamethasone in wild-type mice led to substantial shifts in gut microbiota over a 4-week period. Furthermore, a significant downregulation of colonic Muc2 gene expression was observed after treatment. Muc2-knockout mice harbored a proinflammatory environment of gut microbes, characterized by the increase or decrease in prevalence of specific microbiota populations such as Clostridiales and Lactobacillaceae, respectively. This colitogenic phenotype was transmissible to IL10-knockout mice, a genetically susceptible model of colonic inflammatory disorders. Microbiota from donors pretreated with dexamethasone, however, ameliorated symptoms of inflammation. Commensal gut bacteria may be a key mediator of the anti-inflammatory effects observed in the large intestine after glucocorticoid exposure. These findings underscore the notion that intestinal microbes comprise a "microbial organ" essential for host physiology that can be targeted by therapeutic approaches to restore intestinal homeostasis.

Crohn Disease: Epidemiology, Diagnosis, and Management.

PubMed

Feuerstein, Joseph D; Cheifetz, Adam S

2017-07-01

Crohn disease is a chronic idiopathic inflammatory bowel disease condition characterized by skip lesions and transmural inflammation that can affect the entire gastrointestinal tract from the mouth to the anus. For this review article, we performed a review of articles in PubMed through February 1, 2017, by using the following Medical Subject Heading terms: crohns disease, crohn's disease, crohn disease, inflammatory bowel disease, and inflammatory bowel diseases. Presenting symptoms are often variable and may include diarrhea, abdominal pain, weight loss, nausea, vomiting, and in certain cases fevers or chills. There are 3 main disease phenotypes: inflammatory, structuring, and penetrating. In addition to the underlying disease phenotype, up to a third of patients will develop perianal involvement of their disease. In addition, in some cases, extraintestinal manifestations may develop. The diagnosis is typically made with endoscopic and/or radiologic findings. Disease management is usually with pharmacologic therapy, which is determined on the basis of disease severity and underlying disease phenotype. Although the goal of management is to control the inflammation and induce a clinical remission with pharmacologic therapy, most patients will eventually require surgery for their disease. Unfortunately, surgery is not curative and patients still require ongoing therapy even after surgery for disease recurrence. Importantly, given the risks of complications from both Crohn disease and the medications used to treat the disease process, primary care physicians play an important role in optimizing the preventative care management to reduce the risk of complications. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged Sickle Cell Disease mice

PubMed Central

Bennewitz, Margaret F; Watkins, Simon C; Sundd, Prithu

2014-01-01

Sickle cell disease (SCD) is a genetic disorder that leads to red blood cell (RBC) sickling, hemolysis and the upregulation of adhesion molecules on sickle RBCs. Chronic hemolysis in SCD results in a hyper-inflammatory state characterized by activation of circulating leukocytes, platelets and endothelial cells even in the absence of a crisis. A crisis in SCD is often triggered by an inflammatory stimulus and can lead to the acute chest syndrome (ACS), which is a type of lung injury and a leading cause of mortality among SCD patients. Although it is believed that pulmonary vaso-occlusion could be the phenomenon contributing to the development of ACS, the role of vaso-occlusion in ACS remains elusive. Intravital imaging of the cremaster microcirculation in SCD mice has been instrumental in establishing the role of neutrophil-RBC-endothelium interactions in systemic vaso-occlusion; however, such studies, although warranted, have never been done in the pulmonary microcirculation of SCD mice. Here, we show that two-photon excitation fluorescence microscopy can be used to perform quantitative analysis of neutrophil and RBC trafficking in the pulmonary microcirculation of SCD mice. We provide the experimental approach that enables microscopic observations under physiological conditions and use it to show that RBC and neutrophil trafficking is comparable in SCD and control mice in the absence of an inflammatory stimulus. The intravital imaging scheme proposed in this study can be useful in elucidating the cellular and molecular mechanism of pulmonary vaso-occlusion in SCD mice following an inflammatory stimulus. PMID:25995970

Immunohistochemical expression of interleukin-2 receptor and interleukin-6 in patients with prostate cancer and benign prostatic hyperplasia: association with asymptomatic inflammatory prostatitis NIH category IV.

PubMed

Engelhardt, Paul Friedrich; Seklehner, Stephan; Brustmann, Hermann; Lusuardi, Lukas; Riedl, Claus R

2015-04-01

This study prospectively investigated the immunohistochemical expression of interleukin-2 receptor (IL-2R) and interleukin-6 (IL-6) in patients with prostate cancer and benign prostatic hyperplasia (BPH), and a possible association of these conditions with asymptomatic inflammatory prostatitis National Institutes of Health (NIH) category IV. The study included 139 consecutive patients who underwent transurethral resection of the prostate and transvesical enucleation of the prostate (n = 82) or radical prostatectomy (n = 57). To characterize inflammatory changes the criteria proposed by Irani et al. [J Urol 1997;157:1301-3] were used. IL-2R and IL-6 expression was studied by a standard immunohistochemical method. Results were correlated with tumour, node, metastasis stage, Gleason scores, total prostate-specific antigen, International Prostate Symptom Score and body mass index. IL-2R and IL-6 expression was significantly higher in neoplastic prostate cancer tissue than in normal tissue of prostate cancer patients (p < 0.001 and p < 0.04, respectively). Prostate cancer patients with prostatitis showed significantly higher IL-2R expression than those without inflammation (p < 0.03). In patients with BPH, expression of IL-2R as well as IL-6 was higher in patients with prostatitis than in those without (p < 0.01 and p < 0.02, respectively). IL-2R and IL-6 expression was significantly higher in prostate cancer tissue than in normal tissue. Patients with asymptomatic inflammatory prostatitis NIH category IV showed significantly greater activity.

Microemulsion-Based Topical Hydrogels of Tenoxicam for Treatment of Arthritis.

PubMed

Goindi, Shishu; Narula, Manleen; Kalra, Atin

2016-06-01

Tenoxicam (TNX) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, backache and pain. However, prolonged oral use of this drug is associated with gastrointestinal adverse events like peptic ulceration, thus necessitating its development as topical formulation that could obviate the adverse effects and improve patient compliance. The present study was aimed at development of microemulsion-based formulations of TNX for topical delivery at the affected site. The pseudoternary phase diagrams were developed and microemulsion formulations were prepared using Captex 300/oleic acid as oil, Tween 80 as surfactant and n-butanol/ethanol as co-surfactant. Optimized microemulsions were characterized for drug content, droplet size, viscosity, pH and zeta potential. The ex vivo permeation studies through Laca mice skin were performed using Franz diffusion cell assembly, and the permeation profile of the microemulsion formulation was compared with aqueous suspension of drug and drug incorporated in conventional cream. Microemulsion formulations of TNX showed significantly higher (p < 0.001) mean cumulative percent permeation values in comparison to conventional cream and suspension of drug. In vivo anti-arthritic and anti-inflammatory activity of the developed TNX formulations was evaluated using various inflammatory models such as air pouch model, xylene-induced ear edema, cotton pellet granuloma and carrageenan-induced inflammation. Microemulsion formulations were found to be superior in controlling inflammation as compared to conventional topical dosage forms and showed efficacy equivalent to oral formulation. Results suggest that the developed microemulsion formulations may be used for effective topical delivery of TNX to treat various inflammatory conditions.

Does physical activity affect quality of life, disease symptoms and immune measures in patients with inflammatory bowel disease? A systematic review.

PubMed

Packer, N; Hoffman-Goetz, L; Ward, G

2010-03-01

Inflammatory bowel diseases (IBD) are a group of chronic, episodic inflammatory conditions of the large and small intestines. Individuals with IBD have been reported to use physical activity (PA) as a complementary therapy although the effectiveness of PA for reducing disease burden in patients with IBD is not known. The review objective is to evaluate published studies on physical activity and IBD focusing on quality of life, disease burden markers and immunological outcomes. A literature search was carried out using MEDLINE, WEB OF SCIENCE, CINHAL, and SCOPUS (to December 2008). Studies were included if they 1) were provided in English; 2) dealt with IBD in humans; 3) focused on the outcome measures of health related quality of life, clinical disease indicators or immune function; and 4) included PA as a primary intervention for IBD cases. In total, 7 studies were included in this systematic review: 5 were on PA and quality of life measures and inflammatory disease markers, and 2 on PA and immune measures. Four studies showed that PA significantly increased quality of life for IBD patients as assessed by various questionnaires. PA was also associated with decreased disease activity. There was no evidence that PA affected immune outcomes in patients with IBD. The role of PA as an adjunctive therapy for patients with IBD has not been well characterized in the literature. However, there is some evidence that PA may improve quality of life and reduce disease activity in patients with IBD.

Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis.

PubMed

Kjelgaard-Petersen, Cecilie; Siebuhr, Anne Sofie; Christiansen, Thorbjørn; Ladel, Christoph; Karsdal, Morten; Bay-Jensen, Anne-Christine

2015-01-01

Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model.

Acute Treatment of Migraine

PubMed Central

ÖZTÜRK, Vesile

2013-01-01

Migraine is one of the most frequent disabling neurological conditions with a major impact on the patient’s quality of life. Migraine has been described as a chronic disorder that characterized with attacks. Attacks are characterized by moderate–severe, often unilateral, pulsating headache attacks, typically lasting 4 to 72 hours. Migraine remains underdiagnosed and undertreated despite advances in the understanding of its pathophysiology. This article reviews management of migraine acute pharmacological treatment. Currently, for the acute treatment of migraine attacks, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans (serotonin 5HT1B/1D receptor agonists) are recommended. Before intake of NSAID and triptans, metoclopramide or domperidone is useful. In very severe attacks, subcutaneous sumatriptan is first choice. The patient should be treated early in the attack, use an adequate dose and formulation of a medication. Ideally, acute therapy should be restricted to no more than 2 to 3 days per week to avoid medication overuse. PMID:28360580

Increased Neutrophil Secretion Induced by NLRP3 Mutation Links the Inflammasome to Azurophilic Granule Exocytosis

PubMed Central

Johnson, Jennifer L.; Ramadass, Mahalakshmi; Haimovich, Ariela; McGeough, Matthew D.; Zhang, Jinzhong; Hoffman, Hal M.; Catz, Sergio D.

2017-01-01

Heterozygous mutations in the NLRP3 gene in patients with cryopyrin associated periodic syndrome (CAPS) lead to hyper-responsive inflammasome function. CAPS is a systemic auto-inflammatory syndrome characterized by the activation of the innate immune system induced by elevated pro-inflammatory cytokines, but the involvement of selective innate immune cells in this process is not fully understood. Neutrophil secretion and the toxic components of their granules are mediators of inflammation associated with several human diseases and inflammatory conditions. Here, using the Nlrp3A350V inducible mouse model (MWS CreT) that recapitulates human patients with the A352V mutation in NLRP3 observed in the Muckle-Wells sub-phenotype of CAPS, we studied the relationship between hyper-activation of the inflammasome and neutrophil exocytosis. Using a flow cytometry approach, we show that Nlrp3A350V (MWS) neutrophils express normal basal levels of CD11b at the plasma membrane and that the upregulation of CD11b from secretory vesicles in response to several plasma membrane or endocytic agonist including the bacterial-derived mimetic peptide formyl-Leu-Met-Phe (fMLF) and the unmethylated oligonucleotide CpG is normal in MWS neutrophils. Significant but modest CD11b upregulation in MWS neutrophils compared to wild type was only observed in response to GM-CSF and CpG. The same pattern was observed for the secretion of matrix metalloproteinase-9 (MMP-9) from gelatinase granules in that MMP-9 secretion in MWS neutrophils was not different from that observed in wild-type neutrophils except when stimulated with GM-CSF and CpG. In contrast, azurophilic granule secretion, whose cargoes constitute the most toxic secretory and pro-inflammatory factors of the neutrophil, was markedly dysregulated in MWS neutrophils under both basal and stimulated conditions. This could not be attributed to paracrine effects of secretory cytokines because IL-1β secretion by neutrophils was undetectable under these experimental conditions. The increased azurophilic granule exocytosis in MWS neutrophils was attenuated by treatment with the neutrophil exocytosis inhibitor Nexinhib20. In agreement with a possible neutrophil contribution to systemic inflammation in CAPS, the levels of neutrophil secretory proteins were significantly elevated in the plasma from Nlrp3A350V mice. Altogether, our data indicates an azurophilic granule-selective dysregulation of neutrophil exocytosis in CAPS. PMID:29322034

Inflammatory cells implicated in neoplasia development in idiopathic inflammatory bowel disease.

PubMed

Hashash, Jana G; Hartman, Douglas J

2017-11-10

The inflammatory mechanisms that lead to the clinical symptoms that are grouped under the term inflammatory bowel disease have not been fully characterized. Although a specific mechanism has not been identified, inflammatory bowel disease is believed to be related to an inability by the immune system to shut active inflammation within the intestine. Many contributing factors have been implicated in the disease process. Based on population studies, patients with inflammatory bowel disease have an increased risk for neoplastic development. Although no specific immune cell has been implicated in neoplastic development within this patient population, several immune cells have been implicated as possible etiologies in inflammatory bowel disease. In this review, we will review the clinical evidence about the risk for neoplastic development in inflammatory bowel disease and the current clinical guidelines to survey this patient population. We will also review the pathologic assessment of inflammation within this patient population as well the underlying immune cells and cytokines that have been implicated in the etiology of inflammatory bowel disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

PubMed Central

Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

2015-01-01

Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

MHC Class I Immune Proteins Are Critical for Hippocampus-Dependent Memory and Gate NMDAR-Dependent Hippocampal Long-Term Depression

ERIC Educational Resources Information Center

Nelson, P. Austin; Sage, Jennifer R.; Wood, Suzanne C.; Davenport, Christopher M.; Anagnostaras, Stephan G.; Boulanger, Lisa M.

2013-01-01

Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that…

Diet and Inflammation: Possible Effects on Immunity, Chronic Diseases, and Life Span.

PubMed

Ricordi, Camillo; Garcia-Contreras, Marta; Farnetti, Sara

2015-01-01

Chronic inflammation negatively impacts all physiological functions, causing an array of degenerative conditions including diabetes; cancer; cardiovascular, osteo-articular, and neurodegenerative diseases; autoimmunity disorders; and aging. In particular, there is a growing knowledge of the role that gene transcription factors play in the inflammatory process. Obesity, metabolic syndrome, and diabetes represent multifactorial conditions resulting from improper balances of hormones and gene expression. In addition, these conditions have a strong inflammatory component that can potentially be impacted by the diet. It can reduce pro-inflammatory eicosanoids that can alter hormonal signaling cascades to the modulation of the innate immune system and gene transcription factors. Working knowledge of the impact of how nutrients, especially dietary fatty acids and polyphenols, can impact these various molecular targets makes it possible to develop a general outline of an anti-inflammatory diet that offers a unique, nonpharmacological approach in treating obesity, metabolic syndrome, and diabetes. Several important bioactive dietary components can exert their effect through selected inflammatory pathways that can affect metabolic and genetic changes. In fact, dietary components that can modulate glucose and insulin levels, as well as any other mediator that can activate nuclear factor-kB, can also trigger inflammation through common pathway master switches.

Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways

PubMed Central

Manteiga, Sara; Lee, Kyongbum

2016-01-01

Background: A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals’ effects on adult adipose tissue. Objectives: Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. Methods: We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Results: Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor’s activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Conclusions: Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ. Citation: Manteiga S, Lee K. 2017. Monoethylhexyl phthalate elicits an inflammatory response in adipocytes characterized by alterations in lipid and cytokine pathways. Environ Health Perspect 125:615–622; http://dx.doi.org/10.1289/EHP464 PMID:27384973

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential*

PubMed Central

Bloom, Joshua; Metz, Christine; Nalawade, Saisha; Casabar, Julian; Cheng, Kai Fan; He, Mingzhu; Sherry, Barbara; Coleman, Thomas; Forsthuber, Thomas; Al-Abed, Yousef

2016-01-01

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in a broad range of inflammatory and oncologic diseases. MIF is unique among cytokines in terms of its release profile and inflammatory role, notably as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In addition, it exhibits a catalytic tautomerase activity amenable to the design of high affinity small molecule inhibitors. Although several classes of these compounds have been identified, biologic characterization of these molecules remains a topic of active investigation. In this study, we used in vitro LPS-driven assays to characterize representative molecules from several classes of MIF inhibitors. We determined that MIF inhibitors exhibit distinct profiles of anti-inflammatory activity, especially with regard to TNFα. We further investigated a molecule with relatively low anti-inflammatory activity, compound T-614 (also known as the anti-rheumatic drug iguratimod), and found that, in addition to exhibiting selective MIF inhibition in vitro and in vivo, iguratimod also has additive effects with glucocorticoids. Furthermore, we found that iguratimod synergizes with glucocorticoids in attenuating experimental autoimmune encephalitis, a model of multiple sclerosis. Our work identifies iguratimod as a valuable new candidate for drug repurposing to MIF-relevant diseases, including multiple sclerosis. PMID:27793992

Characterization and Anti-Inflammatory Potential of an Exopolysaccharide from Submerged Mycelial Culture of Schizophyllum commune

PubMed Central

Du, Bin; Yang, Yuedong; Bian, Zhaoxiang; Xu, Baojun

2017-01-01

Background and Purpose: Mushroom polysaccharides have attracted attention in food and pharmacology fields because of their many biological activities. The structure characterization and anti-inflammatory activity of exopolysaccharide from Schizophyllum commune were evaluated in present study. Methods: An exopolysaccharide from a submerged mycelial fermentation of S. commune was obtained using DEAE-52 cellulose and Sephadex G-150 chromatography. The molecular weight (MW), monosaccharide compositions, chemical compositions, methylation analysis, circular dichroism studies, Fourier transform infrared spectroscopy, nuclear magnetic resonance (NMR) spectra, scanning electron microscopy (SEM), and atomic force microscopy were investigated. Results: It was a homogeneous protein-bound heteropolysaccharide with MW of 2,900 kDa. The exopolysaccharide contained a β-(1→3) glycosidic backbone, (1→4)- and (1→6)- glycosidic side chain, and high amount of glucose. The anti-inflammatory activity of exopolysaccharide was assessed by inhibiting the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and 5- lipoxygenase (5-LOX) from macrophages. This exopolysaccharide significantly (p < 0.05) inhibited lipopolysaccharides-induced iNOS expression levels in the cells in a dose-dependent manner. Conclusion: It indicated significant anti-inflammatory effects, which showed that exopolysaccharide might be exploited as an effective anti-inflammatory agent for application in NO-related disorders such as inflammation and cancer. PMID:28555107

Screening and Characterization of Lactic Acid Bacteria Strains with Anti-inflammatory Activities through in vitro and Caenorhabditis elegans Model Testing

PubMed Central

Park, Mi Ri; Kim, Younghoon; Lee, Myung-Ki

2015-01-01

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities. PMID:26761805

The Immune Response and the Pathogenesis of Idiopathic Inflammatory Myositis: a Critical Review.

PubMed

Ceribelli, Angela; De Santis, Maria; Isailovic, Natasa; Gershwin, M Eric; Selmi, Carlo

2017-02-01

The pathogenesis of idiopathic inflammatory myositis (IIMs, including polymyositis and dermatomyositis) remains largely enigmatic, despite advances in the study of the role played by innate immunity, adaptive immunity, genetic predisposition, and environmental factors in an orchestrated response. Several factors are involved in the inflammatory state that characterizes the different forms of IIMs which share features and mechanisms but are clearly different with respect to the involved sites and characteristics of the inflammation. Cellular and non-cellular mechanisms of both the immune and non-immune systems have been identified as key regulators of inflammation in polymyositis/dermatomyositis, particularly at different stages of disease, leading to the fibrotic state that characterizes the end stage. Among these, a special role is played by an interferon signature and complement cascade with different mechanisms in polymyositis and dermatomyositis; these differences can be identified also histologically in muscle biopsies. Numerous cellular components of the adaptive and innate immune response are present in the site of tissue inflammation, and the complexity of idiopathic inflammatory myositis is further supported by the involvement of non-immune mechanisms such as hypoxia and autophagy. The aim of this comprehensive review is to describe the major pathogenic mechanisms involved in the onset of idiopathic inflammatory myositis and to report on the major working hypothesis with therapeutic implications.

Inflammatory activity in Crohn disease: ultrasound findings.

PubMed

Migaleddu, Vincenzo; Quaia, Emilio; Scano, Domenico; Virgilio, Giuseppe

2008-01-01

Improvements in the ultrasound examination of bowel disease have registered in the last years the introduction of new technologies regarding high frequency probes (US), highly sensitive color or power Doppler units (CD-US), and the development of new non-linear technologies that optimize detection of contrast agents. Contrast-enhanced ultrasound (CE-US) most importantly increases the results in sonographic evaluation of Crohn disease inflammatory activity. CE-US has become an imaging modality routinely employed in the clinical practice for the evaluation of parenchymal organs due to the introduction of new generation microbubble contrast agents which persist in the bloodstream for several minutes after intravenous injection. The availability of high frequency dedicated contrast-specific US techniques provide accurate depiction of small bowel wall perfusion due to the extremely high sensitivity of non-linear signals produced by microbubble insonation. In Crohn's disease, CE-US may characterize the bowel wall thickness by differentiating fibrosis from edema and may grade the inflammatory disease activity by assessing the presence and distribution of vascularity within the layers of the bowel wall (submucosa alone or the entire bowel wall). Peri-intestinal inflammatory involvement can be also characterized. CE-US can provide prognostic data concerning clinical recurrence of the inflammatory disease and evaluate the efficacy of drugs treatments.

Secretory IgA in complex with Lactobacillus rhamnosus potentiates mucosal dendritic cell-mediated Treg cell differentiation via TLR regulatory proteins, RALDH2 and secretion of IL-10 and TGF-β

PubMed Central

Mikulic, Josip; Longet, Stéphanie; Favre, Laurent; Benyacoub, Jalil; Corthesy, Blaise

2017-01-01

The importance of secretory IgA in controlling the microbiota is well known, yet how the antibody affects the perception of the commensals by the local immune system is still poorly defined. We have previously shown that the transport of secretory IgA in complex with bacteria across intestinal microfold cells results in an association with dendritic cells in Peyer’s patches. However, the consequences of such an interaction on dendritic cell conditioning have not been elucidated. In this study, we analyzed the impact of the commensal Lactobacillus rhamnosus, alone or associated with secretory IgA, on the responsiveness of dendritic cells freshly recovered from mouse Peyer’s patches, mesenteric lymph nodes, and spleen. Lactobacillus rhamnosus-conditioned mucosal dendritic cells are characterized by increased expression of Toll-like receptor regulatory proteins [including single immunoglobulin interleukin-1 receptor-related molecule, suppressor of cytokine signaling 1, and Toll-interacting molecule] and retinaldehyde dehydrogenase 2, low surface expression of co-stimulatory markers, high anti- versus pro-inflammatory cytokine production ratios, and induction of T regulatory cells with suppressive function. Association with secretory IgA enhanced the anti-inflammatory/regulatory Lactobacillus rhamnosus-induced conditioning of mucosal dendritic cells, particularly in Peyer’s patches. At the systemic level, activation of splenic dendritic cells exposed to Lactobacillus rhamnosus was partially dampened upon association with secretory IgA. These data suggest that secretory IgA, through coating of commensal bacteria, contributes to the conditioning of mucosal dendritic cells toward tolerogenic profiles essential for the maintenance of intestinal homeostasis. PMID:26972771

Is the risk of cardiovascular disease altered with anti-inflammatory therapies? Insights from rheumatoid arthritis

PubMed Central

Kraakman, Michael J; Dragoljevic, Dragana; Kammoun, Helene L; Murphy, Andrew J

2016-01-01

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Atherosclerosis is the most common form of CVD, which is complex and multifactorial with an elevated risk observed in people with either metabolic or inflammatory diseases. Accumulating evidence now links obesity with a state of chronic low-grade inflammation and has renewed our understanding of this condition and its associated comorbidities. An emerging theme linking disease states with atherosclerosis is the increased production of myeloid cells, which can initiate and exacerbate atherogenesis. Although anti-inflammatory drug treatments exist and have been successfully used to treat inflammatory conditions such as rheumatoid arthritis (RA), a commonly observed side effect is dyslipidemia, inadvertently, a major risk factor for the development of atherosclerosis. The mechanisms leading to dyslipidemia associated with anti-inflammatory drug use and whether CVD risk is actually increased by this dyslipidemia are of great therapeutic importance and currently remain poorly understood. Here we review recent data providing links between inflammation, hematopoiesis, dyslipidemia and CVD risk in the context of anti-inflammatory drug use. PMID:27350883

Low Level Light Could Work on Skin Inflammatory Disease: A Case Report on Refractory Acrodermatitis Continua

PubMed Central

Choi, Mira; Na, Se Young; Cho, Soyun

2011-01-01

Low level laser or light treatment on the various clinical condition is getting considerable attention now. However, there has been no report about the clinical effect of low level polarized polychromatic noncoherent light (LPPL) on the inflammatory skin disease. We experienced a case of acrodermatitis continua in a pregnant woman refractory to any conventional treatment including the most potent topical steroid. She was successfully treated with LPPL. LPPL could be a possible treatment modality producing substantial clinical result in inflammatory skin condition without any side-effect. PMID:21394319

Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System.

PubMed

Leszek, Jerzy; Barreto, George E; Gąsiorowski, Kazimierz; Koutsouraki, Euphrosyni; Ávila-Rodrigues, Marco; Aliev, Gjumrakch

2016-01-01

Chronic inflammation is characterized by longstanding microglial activation followed by sustained release of inflammatory mediators, which aid in enhanced nitrosative and oxidative stress. The sustained release of inflammatory mediators propels the inflammatory cycle by increased microglial activation, promoting their proliferation and thus stimulating enhanced release of inflammatory factors. Elevated levels of several cytokines and chronic neuroinflammation have been associated with many neurodegenerative disorders of central nervous system like age-related macular degeneration, Alzheimer disease, multiple sclerosis, Parkinson's disease, Huntington' disease, and tauopathies. This review highlights the basic mechanisms of neuroinflammation, the characteristics of neurodegenerative diseases, and the main immunologic responses in CNS neurodegenerative disorders. A comprehensive outline for the crucial role of microglia in neuroinflammation and neurodegeneration and the role of Toll-like receptor signalling in coexistence of inflammatory mechanisms and oxidative stress as major factors responsible for progression of neurodegeneration have also been presented.

Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

NASA Astrophysics Data System (ADS)

Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

2005-02-01

Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

Host Responses to Malassezia spp. in the Mammalian Skin

PubMed Central

Sparber, Florian; LeibundGut-Landmann, Salomé

2017-01-01

The skin of mammalian organisms is home for a myriad of microbes. Many of these commensals are thought to have beneficial effects on the host by critically contributing to immune homeostasis. Consequently, dysbiosis can have detrimental effects for the host that may manifest with inflammatory diseases at the barrier tissue. Besides bacteria, fungi make an important contribution to the microbiota and among these, the yeast Malassezia widely dominates in most areas of the skin in healthy individuals. There is accumulating evidence that Malassezia spp. are involved in a variety of skin disorders in humans ranging from non- or mildly inflammatory conditions such as dandruff and pityriasis versicolor to more severe inflammatory skin diseases like seborrheic eczema and atopic dermatitis. In addition, Malassezia is strongly linked to the development of dermatitis and otitis externa in dogs. However, the association of Malassezia spp. with such diseases remains poorly characterized. Until now, studies on the fungus–host interaction remain sparse and they are mostly limited to experiments with isolated host cells in vitro. They suggest a multifaceted crosstalk of Malassezia spp. with the skin by direct activation of the host via conserved pattern recognition receptors and indirectly via the release of fungus-derived metabolites that can modulate the function of hematopoietic and/or non-hematopoietic cells in the barrier tissue. In this review, we discuss our current understanding of the host response to Malassezia spp. in the mammalian skin. PMID:29213272

Host Responses to Malassezia spp. in the Mammalian Skin.

PubMed

Sparber, Florian; LeibundGut-Landmann, Salomé

2017-01-01

The skin of mammalian organisms is home for a myriad of microbes. Many of these commensals are thought to have beneficial effects on the host by critically contributing to immune homeostasis. Consequently, dysbiosis can have detrimental effects for the host that may manifest with inflammatory diseases at the barrier tissue. Besides bacteria, fungi make an important contribution to the microbiota and among these, the yeast Malassezia widely dominates in most areas of the skin in healthy individuals. There is accumulating evidence that Malassezia spp. are involved in a variety of skin disorders in humans ranging from non- or mildly inflammatory conditions such as dandruff and pityriasis versicolor to more severe inflammatory skin diseases like seborrheic eczema and atopic dermatitis. In addition, Malassezia is strongly linked to the development of dermatitis and otitis externa in dogs. However, the association of Malassezia spp. with such diseases remains poorly characterized. Until now, studies on the fungus-host interaction remain sparse and they are mostly limited to experiments with isolated host cells in vitro . They suggest a multifaceted crosstalk of Malassezia spp. with the skin by direct activation of the host via conserved pattern recognition receptors and indirectly via the release of fungus-derived metabolites that can modulate the function of hematopoietic and/or non-hematopoietic cells in the barrier tissue. In this review, we discuss our current understanding of the host response to Malassezia spp. in the mammalian skin.

Tocilizumab for uncontrollable systemic inflammatory response syndrome complicating adult-onset Still disease

PubMed Central

Masui-Ito, Asami; Okamoto, Ryuji; Ikejiri, Kaoru; Fujimoto, Mika; Tanimura, Muneyoshi; Nakamori, Shiro; Murata, Tomohiro; Ishikawa, Eiji; Yamada, Norikazu; Imai, Hiroshi; Ito, Masaaki

2017-01-01

Abstract Rationale: Adult-onset Still disease (AOSD) is a rare systemic inflammatory disease of unknown etiology characterized by evanescent salmon-pink rash, fever spikes, arthralgia, and lymphadenopathy. AOSD usually has a good prognosis, but it can sometimes be fatal, especially when it is complicated by systemic inflammatory response syndrome (SIRS) and multiple organ failure. Patient concerns: A previously healthy 26-year-old woman was referred to our hospital for persistent high fever and mild systemic edema. Five days later, the patient presented with dyspnea, hypotension, and anuria. Anasarca developed with massive pleural effusion, ascites, and systemic edema, resulting in an increase of 47 kg in body weight. Diagnoses: The patient was diagnosed as AOSD after infection, malignancy, hematologic disorders, and other autoimmune diseases were excluded. Interventions: We administered tocilizumab, an IL-6 receptor inhibitor, intravenously in addition to cyclosporine, prednisolone, plasma exchange, and continuous hemodiafiltration. Outcomes: The patient's systemic condition improved. After stabilization by all medications, the patient was managed and responded to tocilizumab alone. To the best of our knowledge, this was the first case of severe SIRS complicating AOSD that was successfully treated with an anti- IL-6 receptor antibody. Lessons: SIRS should not be overlooked in a patient with steroid-resistant AOSD and edema. Inhibitors of the IL-6 receptor can be used safely and effectively to control AOSD complicated with severe SIRS. PMID:28723802

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients

PubMed Central

Sundblad, Victoria; Quintar, Amado A.; Morosi, Luciano G.; Niveloni, Sonia I.; Cabanne, Ana; Smecuol, Edgardo; Mauriño, Eduardo; Mariño, Karina V.; Bai, Julio C.; Maldonado, Cristina A.; Rabinovich, Gabriel A.

2018-01-01

Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn’s disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings. PMID:29545799

Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients.

PubMed

Sundblad, Victoria; Quintar, Amado A; Morosi, Luciano G; Niveloni, Sonia I; Cabanne, Ana; Smecuol, Edgardo; Mauriño, Eduardo; Mariño, Karina V; Bai, Julio C; Maldonado, Cristina A; Rabinovich, Gabriel A

2018-01-01

Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn's disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.

The Inflammasome and Danger Molecule Signaling: At the Crossroads of Inflammation and Pathogen Persistence in the Oral Cavity

PubMed Central

Yilmaz, Özlem; Lee, Kyu Lim

2014-01-01

Inflammasomes are an oligomeric assembly of multiprotein complexes that activate the caspase-1-dependent maturation and the subsequent secretion of inflammatory interleukin-1β and interleukin-18 cytokines in response to a ‘danger signal’ in vertebrates. The assessment of their significance continues to grow rapidly as the complex biology of various chronic inflammatory conditions are better dissected. Increasing evidence links inflammasomes and host-derived small ‘danger molecule ATP’-signaling strongly with the modulation of the host immune response by microbial colonizers as well as potential altering of the microbiome structure and inter-microbial interactions in host. All of these factors eventually lead to the destructive chronic inflammatory disease state. In the oral cavity, a highly dynamic and multifaceted interplay takes place between the endogenous danger molecule signaling and colonizing microbes on the mucosal surfaces. This interaction may redirect the local microenvironment to favor the conversion of the resident microbiome towards pathogenicity. This review outlines the major components of the known inflammasome complexes/mechanisms and highlights their regulation, in particular, by oral microorganisms in relation to the periodontal disease pathology. Better characterizations of the cellular and molecular biology of the inflammasome will likely present important potential therapeutic targets in the treatment and prevention of periodontal disease as well as other debilitating chronic diseases. PMID:26252403

Allergic rhinitis and inflammatory airway disease: interactions within the unified airspace.

PubMed

Marple, Bradley F

2010-01-01

Allergic rhinitis (AR), the most common chronic allergic condition in outpatient medicine, is associated with immense health care costs and socioeconomic consequences. AR's impact may be partly from interacting of respiratory conditions via allergic inflammation. This study was designed to review potential interactive mechanisms of AR and associated conditions and consider the relevance of a bidirectional "unified airway" respiratory inflammation model on diagnosis and treatment of inflammatory airway disease. MEDLINE was searched for pathophysiology and pathophysiological and epidemiologic links between AR and diseases of the sinuses, lungs, middle ear, and nasopharynx. Allergic-related inflammatory responses or neural and systemic processes fostering inflammatory changes distant from initial allergen provocation may link AR and comorbidities. Treating AR may benefit associated respiratory tract comorbidities. Besides improving AR outcomes, treatment inhibiting eosinophil recruitment and migration, normalizing cytokine profiles, and reducing asthma-associated health care use in atopic subjects would likely ameliorate other upper airway diseases such as acute rhinosinusitis, chronic rhinosinusitis (CRS) with nasal polyposis (NP), adenoidal hypertrophy, and otitis media with effusion. Epidemiological concordance of AR with several airway diseases conforms to a bidirectional "unified airway" respiratory inflammation model based on anatomic and histological upper and lower airway connections. Epidemiology and current understanding of inflammatory, humoral, and neural processes make links between AR and disorders including asthma, otitis media, NP, and CRS plausible. Combining AR with associated conditions increases disease burden; worsened associated illness may accompany worsened AR. AR pharmacotherapies include antihistamines, leukotriene antagonists, intranasal corticosteroids, and immunotherapy; treatments attenuating proinflammatory responses may also benefit associated conditions.

Differentiation between inflammatory and neoplastic orbital conditions based on computed tomographic signs.

PubMed

Lederer, Kristina; Ludewig, Eberhard; Hechinger, Harald; Parry, Andrew T; Lamb, Christopher R; Kneissl, Sibylle

2015-07-01

To identify computed tomographic (CT) signs that could be used to differentiate inflammatory from neoplastic orbital conditions in small animals. Fifty-two animals (25 cats, 21 dogs, 4 rabbits, and 2 rodents). Case-control study in which CT images of animals with histopathologic diagnosis of inflammatory (n = 11), neoplastic orbital conditions (n = 31), or normal control animals (n = 10) were reviewed independently by five observers without the knowledge of the history or diagnosis. Observers recorded their observations regarding specific anatomical structures within the orbit using an itemized form containing the following characteristics: definitely normal; probably normal; equivocal; probably abnormal; and definitely abnormal. Results were statistically analyzed using Fleiss' kappa and logistic regression analyses. The overall level of agreement between observers about the presence or absence of abnormal CT signs in animals with orbital disease was poor to moderate, but was highest for observations concerning orbital bones (κ = 0.62) and involvement of the posterior segment (κ = 0.52). Significant associations between abnormalities and diagnosis were found for four structures: Abnormalities affecting orbital bones (odds ratio [OR], 1.7) and anterior ocular structures (OR, 1.5) were predictive of neoplasia, while abnormalities affecting extraconal fat (OR, 1.7) and skin (OR, 1.4) were predictive of inflammatory conditions. Orbital CT is an imaging test with high specificity. Fat stranding, a CT sign not previously emphasized in veterinary medicine, was significantly associated with inflammatory conditions. Low observer agreement probably reflects the limited resolution of CT for small orbital structures. © 2014 American College of Veterinary Ophthalmologists.

Anti-inflammatory drugs interacting with Zn(II), Cd(II) and Pt(II) metal ions.

PubMed

Dendrinou-Samara, C; Tsotsou, G; Ekateriniadou, L V; Kortsaris, A H; Raptopoulou, C P; Terzis, A; Kyriakidis, D A; Kessissoglou, D P

1998-09-01

Complexes of Zn(II), Cd(II) and Pt(II) metal ions with the anti-inflammatory drugs, 1-methyl-5-(p-toluoyl)-1H-pyrrole-2-acetic acid (Tolmetin), alpha-methyl-4-(2-methylpropyl)benzeneacetic acid (Ibuprofen), 6-methoxy-alpha-methylnaphthalene-2-acetic acid (Naproxen) and 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid (indomethacin) have been synthesized and characterized. In the structurally characterized Cd(naproxen)2 complex the anti-inflammatory drugs acts as bidentate chelate ligand coordinatively bound to metal ions through the deprotonated carboxylate group. Crystal data for 1: [C32H26O8Cd], orthorhombic, space group P22(1)2(1), a = 5.693(2) (A), b = 8.760(3) (A), c = 30.74(1) (A), V = 1533(1) A3, Z = 2. Antibacterial and growth inhibitory activity is higher than that of the parent ligands or the platinum(II) diamine compounds.

Metabolomic characterization of laborers exposed to welding fumes.

PubMed

Wang, Kuo-Ching; Kuo, Ching-Hua; Tian, Tze-Feng; Tsai, Mong-Hsun; Chiung, Yin-Mei; Hsiech, Chun-Ming; Tsai, Sung-Jeng; Wang, San-Yuan; Tsai, Dong-Ming; Huang, Chiang-Ching; Tseng, Y Jane

2012-03-19

The complex composition of welding fumes, multiplicity of molecular targets, diverse cellular effects, and lifestyles associated with laborers vastly complicate the assessment of welding fume exposure. The urinary metabolomic profiles of 35 male welders and 16 male office workers at a Taiwanese shipyard were characterized via (1)H NMR spectroscopy and pattern recognition methods. Blood samples for the same 51 individuals were also collected, and the expression levels of the cytokines and other inflammatory markers were examined. This study dichotomized the welding exposure variable into high (welders) versus low (office workers) exposures to examine the differences of continuous outcome markers-metabolites and inflammatory markers-between the two groups. Fume particle assessments showed that welders were exposed to different concentrations of chromium, nickel, and manganese particles. Multivariate statistical analysis of urinary metabolomic patterns showed higher levels of glycine, taurine, betaine/TMAO, serine, S-sulfocysteine, hippurate, gluconate, creatinine, and acetone and lower levels of creatine among welders, while only TNF-α was significantly associated with welding fume exposure among all cytokines and other inflammatory markers measured. Of the identified metabolites, the higher levels of glycine, taurine, and betaine among welders were suspected to play some roles in modulating inflammatory and oxidative tissue injury processes. In this metabolomics experiment, we also discovered that the association of the identified metabolites with welding exposure was confounded by smoking, but not with drinking, which is a finding consistent with known modified response of inflammatory markers among smokers. Our results correspond with prior studies that utilized nonmetabolomic analytical techniques and suggest that the metabolomic profiling is an efficient method to characterize the overall effect of welding fume exposure and other confounders. © 2012 American Chemical Society

Interaction of obesity and inflammatory bowel disease

PubMed Central

Harper, Jason W; Zisman, Timothy L

2016-01-01

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management. PMID:27672284

Blood lipids, infection, and inflammatory markers in the Tsimane of Bolivia.

PubMed

Vasunilashorn, Sarinnapha; Crimmins, Eileen M; Kim, Jung Ki; Winking, Jeff; Gurven, Michael; Kaplan, Hillard; Finch, Caleb E

2010-01-01

Little is known about blood cholesterol (blood-C) levels under conditions of infection and limited diet. This study examines blood-C and markers of infection and inflammation in the Tsimane of the Bolivian Amazon, indigenous forager farmers living in conditions that model preindustrial European populations by their short life expectancy, high load of infections and inflammation, and limited diets. We use multivariate models to determine the relationships between lipid levels and markers of infection and inflammation. Adult Tsimane (N = 418, age 20-84) were characterized for blood lipids, cells, and inflammatory markers in relation to individual loads of parasites and village region. Most of the Tsimane (60%) carried at least one parasite species, averaging 1.3 species per person. Serum high-density lipoprotein cholesterol (HDL-C), total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) were below the U.S. norms and varied inversely with markers of infection and inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), immunoglobulin (Ig) E and eosinophil count. Although no relationship of parasite load to blood-C was found, there was an association between anemia and parasite prevalence. We conclude that the highly infected environment of the Tsimane is related to low levels of blood total-C, HDL-C, and LDL-C. This may suggest a potential reason why arterial disease is largely absent in the Tsimane. © 2010 Wiley-Liss, Inc.

The efficacy of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) and a mixture of topical hAMMSC-CM + vitamin C and hAMMSC-CM + vitamin E on chronic plantar ulcers in leprosy:a randomized control trial.

PubMed

Prakoeswa, C R S; Natallya, F R; Harnindya, D; Thohiroh, A; Oktaviyanti, R N; Pratiwi, K D; Rubianti, M A; Yogatri, B; Primasari, P I; Herwanto, N; Alinda, M D; Kusumaputra, B H; Astari, L; Listiawan, M Y; Agusni, I; Rantam, F A

2018-05-10

Healing of chronic plantar ulcers in leprosy (CPUL) typically takes a long time due to impaired neurological function, thereby reducing the levels of growth factors and cytokines. Cytokines can be found in metabolite products from amniotic membrane stem cells. Chronic ulcers are frequently characterized by high levels of reactive oxygen species. Vitamin E (α-tocopherol) is widely used in skin lesions, owing to its antioxidant and anti-inflammatory properties. Vitamin C also has antioxidant, anti-inflammatory, and collagen synthesis properties which are useful in wound healing. Herein, we compared the effects of topical human amniotic membrane-mesenchymal stem cell-conditioned medium (hAMMSC-CM) alone and with vitamins C and E on healing of CPUL. In this randomized controlled trial, topical agents were applied every 3 days for up to 8 weeks. Ulcer size, side-effects, and possible complications were monitored weekly. Healing percentage increased each week in all groups. Mean difference in ulcer size was highest in the hAMMSC-CM + vitamin E group, implying better progress of wound healing. There were no side-effects or complications. hAMMSC-CM + vitamin E is best for healing of CPUL.

Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine[S

PubMed Central

Salvatore, Sonia R.; Vitturi, Dario A.; Baker, Paul R. S.; Bonacci, Gustavo; Koenitzer, Jeffrey R.; Woodcock, Steven R.; Freeman, Bruce A.; Schopfer, Francisco J.

2013-01-01

The oxidation and nitration of unsaturated fatty acids transforms cell membrane and lipoprotein constituents into mediators that regulate signal transduction. The formation of 9-NO2-octadeca-9,11-dienoic acid and 12-NO2-octadeca-9,11-dienoic acid stems from peroxynitrite- and myeloperoxidase-derived nitrogen dioxide reactions as well as secondary to nitrite disproportionation under the acidic conditions of digestion. Broad anti-inflammatory and tissue-protective responses are mediated by nitro-fatty acids. It is now shown that electrophilic fatty acid nitroalkenes are present in the urine of healthy human volunteers (9.9 ± 4.0 pmol/mg creatinine); along with electrophilic 16- and 14-carbon nitroalkenyl β-oxidation metabolites. High resolution mass determinations and coelution with isotopically-labeled metabolites support renal excretion of cysteine-nitroalkene conjugates. These products of Michael addition are in equilibrium with the free nitroalkene pool in urine and are displaced by thiol reaction with mercury chloride. This reaction increases the level of free nitroalkene fraction >10-fold and displays a KD of 7.5 × 10−6 M. In aggregate, the data indicates that formation of Michael adducts by electrophilic fatty acids is favored under biological conditions and that reversal of these addition reactions is critical for detecting both parent nitroalkenes and their metabolites. The measurement of this class of mediators can constitute a sensitive noninvasive index of metabolic and inflammatory status. PMID:23620137

Autoimmune/inflammatory syndrome induced by mineral oil: a health problem.

PubMed

Vera-Lastra, Olga; Medina, Gabriela; Cruz-Domínguez, María Pilar; Ramírez, Gabriel Medrano; Blancas, Raymundo Benjamin Priego; Amaro, Ana Lilia Peralta; Martínez, Anabel Villanueva; Delgado, Jesús Sepúlveda; Jara, Luis J

2018-06-01

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wenyao; Li, Xuezhong; Xu, Tong

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferationmore » and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. - Highlights: • Inflammatory BMEs affect the properties of BMFs during mastitis. • BMEs inhibited the proliferation and promoted the migration of BMFs. • BMEs enhanced secretion of inflammatory mediators and deposition of ECM in BMFs. • Changes of the properties of BMFs were mediated by specific signal molecules.« less

Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells

DTIC Science & Technology

2006-11-01

crucial signals in the development of appropriate defenses. However, exaggerated or prolonged release can lead to pathological conditions ( Sabourin ...gene expression of the inflammatory cytokines ( Sabourin et al., 2000). In this study we examined the expression of four major inflammatory...Med., 117, 2S-4S. Sabourin C. L., Petrali, J. P., and Casillas, R. P., 2000: Alterations in inflammatory cytokine gene expression in sulfur mustard

Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease.

PubMed

Tarantino, Giovanni; Finelli, Carmine

2013-10-28

Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing's syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing's syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing's syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing's syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

[Towards new therapeutic paradigms beyond symptom control in the management of inflammatory bowel diseases.

PubMed

Festa, Stefano; Zerboni, Giulia; Aratari, Annalisa; Ballanti, Riccardo; Papi, Claudio

2018-01-01

Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are chronic relapsing conditions that may result in progressive bowel damage, high risk of complications, surgery and permanent disability. The conventional therapeutic approach for inflammatory bowel diseases is based mainly on symptom control. Unfortunately, a symptom-based therapeutic approach has little impact on major long-term disease outcomes. In other chronic disabling conditions such as diabetes, hypertension and rheumatoid arthritis, the development of new therapeutic approaches has led to better outcomes. In this context a "treat to target" strategy has been developed. This strategy is based on identification of high-risk patients, regular assessment of disease activity by means of objective measures, adjustment of treatment to reach the pre-defined target. A treat to target approach has recently been proposed for inflammatory bowel disease with the aim at modifying the natural history of the disease. In this review, the evidence and the limitations of the treat to target paradigm in inflammatory bowel disease are analyzed and discussed.

DADLE enhances viability and anti-inflammatory effect of human MSCs subjected to 'serum free' apoptotic condition in part via the DOR/PI3K/AKT pathway.

PubMed

Reddy, L Vinod Kumar; Sen, Dwaipayan

2017-12-15

Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala 2 , D-Leu 5 ]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. Cell viability was measured using MTT and Annexin V/PI assays. Expressions of pro-apoptotic (Bcl2) and anti-apoptotic genes (Bax/Bad), levels of activated p44/42 MAPK, Akt, PI3-kinase-p110γ and cleaved caspase-3 were determined by qPCR and western blot. Levels of secreted cytokines were measured by ELISA. In comparison to the control, DADLE significantly increased cell survivability under serum deprived condition as confirmed by MTT (71% vs 45%) and Annexin V/PI assays (25.9% vs 3.7%). Significant up-regulation of pro-apoptotic Bcl2 (~2.1 folds), down-regulations of anti-apoptotic Bax/Bad (~2.6/2.7 folds) as well as of cleaved caspase-3, increased expression of PI3kinase subunit p110γ and activation of Akt (Ser473) were observed following DADLE treatment in cells under 'serum deprivation' stress. In addition, DADLE treated hMSCs secreted increased levels of anti-inflammatory cytokines (IL10/IL4/TGF-β) under serum deprived condition. LPS stimulated macrophages showed abated release of pro-inflammatory cytokines (IL1/TNFα/IL6) when grown in hMSC conditioned 'serum deprived' media treated with DADLE. Both the cytoprotective and anti-inflammatory effects of DADLE were inhibited by the DOR specific antagonist naltrindole. The DOR signaling pathway improved cell viability and enhanced anti-inflammatory effect of hMSCs subjected to 'serum deprivation' stress that could have potential therapeutic benefits in reparative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Mexican Arnica (Heterotheca inuloides Cass. Asteraceae: Astereae): Ethnomedical uses, chemical constituents and biological properties.

PubMed

Rodríguez-Chávez, José Luis; Egas, Verónica; Linares, Edelmira; Bye, Robert; Hernández, Tzasna; Espinosa-García, Francisco J; Delgado, Guillermo

2017-01-04

Heterotheca inuloides Cass. (Asteraceae) has been traditionally used to treat a wide range of diseases in Mexico in the treatment of rheumatism, topical skin inflammation, muscular pain colic, and other painful conditions associated with inflammatory processes, additionally has been used to treat dental diseases, and gastrointestinal disorders. This species has also been used for the treatment of cancer and diabetes. This review provides up-to-date information on the botanical characterization, traditional uses, chemical constituents, as well as the biolological activities of H. inuloides. A literature search was conducted by analyzing the published scientific material. Information related to H. inuloides was collected from various primary information sources, including books, published articles in peer-reviewed journals, monographs, theses and government survey reports. The electronic search of bibliographic information was gathered from accepted scientific databases such as Scienfinder, ISI Web of Science, Scielo, LILACS, Redalyc, Pubmed, SCOPUS and Google Scholar. To date, more than 140 compounds have been identified from H. inuloides, including cadinane sesquiterpenes, flavonoids, phytosterols, triterpenes, benzoic acid derivatives, and other types of compounds. Many biological properties associated with H. inuloides. Many studies have shown that the extracts and some compounds isolated from this plant exhibit a broad spectrum of biological activities such as antioxidant, antitumor, anti-inflammatory, cytotoxic, and chelating activities, as well as insecticidal and phytotoxic activity. To date, reports on the toxicity of H. inuloides are limited. A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethnomedical uses of H. inuloides have been recorded in Mexico to treat rheumatism, pain, and conditions associated with inflammatory processes. Pharmacological studies have demonstrated the activity of certain compounds associated with the traditional use of the plant such as the anti-inflammatory and cytotoxic activities of the species. The available literature showed that cadinene sesquiterpenes are the major bioactive components of H. inuloides with potential pharmacological activities. Further investigations are needed to fully understand the mode of action of the major active constituents. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response

PubMed Central

Emanuelsson, Olof; Sennblad, Bengt; Pirmoradian Najafabadi, Mohammad; Folkersen, Lasse; Mälarstig, Anders; Lagergren, Jens; Eriksson, Per; Hamsten, Anders; Odeberg, Jacob

2012-01-01

Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/−LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response. PMID:22384210

A20-binding inhibitor of NF-κB (ABIN1) controls Toll-like receptor-mediated CCAAT/enhancer-binding protein β activation and protects from inflammatory disease.

PubMed

Zhou, Jingran; Wu, Ruiqiong; High, Anthony A; Slaughter, Clive A; Finkelstein, David; Rehg, Jerold E; Redecke, Vanessa; Häcker, Hans

2011-11-01

Toll-like receptors (TLRs) are expressed on innate immune cells and trigger inflammation upon detection of pathogens and host tissue injury. TLR-mediated proinflammatory-signaling pathways are counteracted by partially characterized anti-inflammatory mechanisms that prevent exaggerated inflammation and host tissue damage as manifested in inflammatory diseases. We biochemically identified a component of TLR-signaling pathways, A20-binding inhibitor of NF-κB (ABIN1), which recently has been linked by genome-wide association studies to the inflammatory diseases systemic lupus erythematosus and psoriasis. We generated ABIN1-deficient mice to study the function of ABIN1 in vivo and during TLR activation. Here we show that ABIN1-deficient mice develop a progressive, lupus-like inflammatory disease characterized by expansion of myeloid cells, leukocyte infiltrations in different parenchymatous organs, activated T and B lymphocytes, elevated serum Ig levels, and the appearance of autoreactive antibodies. Kidneys develop glomerulonephritis and proteinuria, reflecting tissue injury. Surprisingly, ABIN1-deficient macrophages exhibit normal regulation of major proinflammatory signaling pathways and mediators but show selective deregulation of the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) and its target genes, such as colony-stimulating factor 3 (Csf3), nitric oxide synthase, inducible (Nos2), and S100 calcium-binding protein A8 (S100a8). Their gene products, which are intimately linked to innate immune cell expansion (granulocyte colony-stimulating factor), cytotoxicity (inducible nitric oxide synthase), and host factor-derived inflammation (S100A8), may explain, at least in part, the inflammatory phenotype observed. Together, our data reveal ABIN1 as an essential anti-inflammatory component of TLR-signaling pathways that controls C/EBPβ activity.

Dexamethasone inhibits high glucose-, TNF-alpha-, and IL-1beta-induced secretion of inflammatory and angiogenic mediators from retinal microvascular pericytes.

PubMed

Nehmé, Alissar; Edelman, Jeffrey

2008-05-01

To characterize the effects of dexamethasone in human retinal pericytes (HRMPs), monocytes (THP-1), and retinal endothelial cells (HRECs) treated with high glucose, TNF-alpha, or IL-1beta. HRMP and HREC phenotypes were verified by growth factor stimulation of intracellular calcium-ion mobilization. Glucocorticoid receptor phosphorylation was assessed with an anti-phospho-Ser(211) glucocorticoid receptor antibody. Secretion of 89 inflammatory and angiogenic proteins were compared in cells incubated with (1) normal (5 mM) or high (25 mM) D-glucose and (2) control medium, TNF-alpha (10 ng/mL), or IL-1beta (10 ng/mL), with or without dexamethasone (1 nM to 1 microM). The proteins were compared by using multianalyte profile testing. HRMPs and HRECs expressed functional PDGFB-R and VEGFR-2, respectively. Dexamethasone induction of glucocorticoid receptor phosphorylation was dose-dependent in all cell types. High glucose increased secretion of inflammatory mediators in HRMPs, but not in HRECs. Dexamethasone dose dependently inhibited secretion of these mediators in HRMPs. For all cells, TNF-alpha and IL-1beta induced a fivefold or more increase in inflammatory and angiogenic mediators; HRMPs secreted the greatest number and level of mediators. Dexamethasone dose dependently inhibited the secretion of multiple proteins from HRMPs and THP-1 cells, but not from HRECs (IC(50) 2 nM to 1 microM). High glucose, TNF-alpha, and IL-1beta induced an inflammatory phenotype in HRMPs, characterized by hypersecretion of inflammatory and angiogenic mediators. Dexamethasone at various potencies blocked hypersecretion of several proteins. Pericytes may be a key therapeutic target in retinal inflammatory diseases, including diabetic retinopathy. Inhibition of pathologic mediators may depend on delivering high levels ( approximately 1 microM) of glucocorticoid to the retina.

A painful stiff neck following an ear, nose, and throat surgical procedure: case report.

PubMed

Pavlidis, Elena; Copioli, Cristiana; Spagnoli, Carlotta; Mazzotta, Silvia; Ormitti, Francesca; Crisi, Girolamo; Pisani, Francesco

2015-02-01

Grisel syndrome is a rare, nontraumatic atlantoaxial subluxation, typical of developmental ages and characterized by head flexion/rotation and painful fixation. Neurological symptoms may occur. It is secondary to head/neck infections and ear, nose, and throat surgery (adenoidectomy, tonsillectomy, and mastoidectomy). Here, we report the case of a child who presented a painful stiff neck following an adenotonsillectomy, with imaging evidencing an atlantoaxial subluxation. The child showed improvement in his condition following a conservative treatment with antibiotics, anti-inflammatory, and analgesic therapy and cervical collar. We believe it is of great significance for clinicians taking into account this peculiar condition in the differential diagnosis of a stiff neck in pediatric patients, thus avoiding misdiagnosis and delays. Indeed, its diagnosis is mainly based on a focused anamnesis associated with the detection of the typical neuroradiological findings. Georg Thieme Verlag KG Stuttgart · New York.

Hemodynamically driven stent strut design.

PubMed

Jiménez, Juan M; Davies, Peter F

2009-08-01

Stents are deployed to physically reopen stenotic regions of arteries and to restore blood flow. However, inflammation and localized stent thrombosis remain a risk for all current commercial stent designs. Computational fluid dynamics results predict that nonstreamlined stent struts deployed at the arterial surface in contact with flowing blood, regardless of the strut height, promote the creation of proximal and distal flow conditions that are characterized by flow recirculation, low flow (shear) rates, and prolonged particle residence time. Furthermore, low shear rates yield an environment less conducive for endothelialization, while local flow recirculation zones can serve as micro-reaction chambers where procoagulant and pro-inflammatory elements from the blood and vessel wall accumulate. By merging aerodynamic theory with local hemodynamic conditions we propose a streamlined stent strut design that promotes the development of a local flow field free of recirculation zones, which is predicted to inhibit thrombosis and is more conducive for endothelialization.

Acetaminophen hepatotoxicity and sterile inflammation: The mechanism of protection of Chlorogenic acid.

PubMed

Jaeschke, Hartmut

2016-01-05

Acetaminophen hepatotoxicity is characterized by extensive necrotic cell death and a sterile inflammatory response. A recent report suggested that a therapeutic intervention with chlorogenic acid, a dietary polyphenolic compound, protects against acetaminophen-induced liver injury by inhibiting the inflammatory injury. The purpose of this letter is to discuss a number of reasons why the protective mechanism of chlorogenic acid against acetaminophen hepatotoxicity does not involve an anti-inflammatory effect and provides an alternative explanation for the observed protection. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pyrrole and Fused Pyrrole Compounds with Bioactivity against Inflammatory Mediators.

PubMed

Said Fatahala, Samar; Hasabelnaby, Sherifa; Goudah, Ayman; Mahmoud, Ghada I; Helmy Abd-El Hameed, Rania

2017-03-17

A new series of pyrrolopyridines and pyrrolopyridopyrimidines have been synthesized from aminocyanopyrroles. The synthesized compounds have been characterized by FTIR, ¹H-NMR and mass spectroscopy. The final compounds have been screened for in vitro pro-inflammatory cytokine inhibitory and in vivo anti-inflammatory activity. The biological results revealed that among all tested compounds some fused pyrroles, namely the pyrrolopyridines 3i and 3l , show promising activity. A docking study of the active synthesized molecules confirmed the biological results and revealed a new binding pose in the COX-2 binding site.

Two new triterpenes from the roots of Pfaffia glomerata.

PubMed

Lian, Lian; Feng, Yuan; Li, Yan-Wu; Bei, Bei; Tang, Ye-Tian; Wang, Hao; Feng, Qing-Mei; Chen, Gang

2018-04-02

Pfaffia paniculata is a commercialized dietary supplement used as the substitute for the Asian ginseng in Brazil. We conducted the systematic isolation of the EtOAc fraction with anti-inflammatory effect and two new triterpenoids, along with 26 known compounds were characterized by means of MS and NMR analysis. Interestingly, the new compound 1 is the first seco-ring triterpenoid reported in the Pfaffia genus. Furthermore, among the known compounds, 14 and 15 exhibited anti-inflammatory activity in Caco-2 cells, but two new compounds showed no anti-inflammatory.

Pre-existing Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced BRONJ Lesions in Mice

PubMed Central

Song, Minju; Alshaikh, Abdullah; Kim, Terresa; Kim, Sol; Dang, Michelle; Mehrazarin, Shebli; Shin, Ki-Hyuk; Kang, Mo; Park, No-Hee; Kim, Reuben H.

2016-01-01

Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ. PMID:27637460

Myelodysplastic syndrome with trisomy 8 associated with Behçet syndrome: an immunologic link to a karyotypic abnormality.

PubMed

Thachil, Jecko V; Salim, Rahuman; Field, Anne; Moots, Robert; Bolton-Maggs, Paula

2008-03-01

Myelodysplastic syndrome (MDS) in children is often associated with chromosomal anomalies and trisomy 8 is a characteristic karyotypic feature in up to 20% of the cases. Behçet disease is a rare multisystem inflammatory disorder characterized by recurrent mouth and genital ulcers. MDS with trisomy 8 has been observed in adult patients with Behçet syndrome with some cases developing prior to the clinical manifestations of the latter. We present a female with a similar association and explain the importance of identifying the coexisting conditions. The immunological abnormalities, which may be observed in MDS and their possible mechanisms, are also discussed. (c) 2007 Wiley-Liss, Inc.

Intravenous Immunoglobulin in the Treatment of Primary Immunodeficiency Diseases.

PubMed

De Ranieri, Deirdre; Fenny, Nana Sarkoah

2017-01-01

Intravenous immunoglobulin (IVIG) has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for more than 50 years. Its role as a therapeutic agent has expanded over the past couple of decades as its anti-inflammatory and immune-modulatory mechanisms of action have been elucidated. It is now used "off-label" to treat other autoimmune diseases. This article focuses on the role of IVIG in the treatment of PIDDs characterized by absent or deficient antibody production. Replacement doses are given on a monthly basis in these conditions as a prophylactic measure to prevent acute and serious bacterial infections. [Pediatr Ann. 2017;46(1):e8-e12.]. Copyright 2017, SLACK Incorporated.

Achilles tendon: US examination

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fornage, B.D.

Real-time ultrasonography (US) using linear-array probes and a stand-off pad as a ''waterpath'' was performed to evaluate the Achilles tendon in 67 patients (including 24 athletes) believed to have acute or chronic traumatic or inflammatory pathologic conditions. Tendons in 23 patients appeared normal on US scans. The 44 abnormal tendons comprised five complete and four partial ruptures, seven instances of postoperative change, and 28 cases of tendonitis. US depiction of the inner structure of the tendon resulted in the diagnosis of focal abnormalities, including partial ruptures, nodules, and calcifications. Tendonitis was characterized by enlargement and decreased echogenicity of the tendon.more » The normal US appearance of the Achilles tendon is described.« less

Oxidants, antioxidants, and respiratory tract lining fluids.

PubMed Central

Cross, C E; van der Vliet, A; O'Neill, C A; Louie, S; Halliwell, B

1994-01-01

Respiratory tract lining fluids (RTLFs) are a heterogeneous group of substances covering the respiratory tract epithelial cells (RTECs) from nasal mucosa to alveoli. Antioxidant contained in the RTLFs can be expected to provide an initial defense against inhaled environmental toxins. The major antioxidants in RTLF include mucin, uric acid, protein (largely albumin), ascorbic acid, and reduced glutathione (GSH). RTLF antioxidants can be augmented by such processes as transudation/exudation of plasma constituents; RTEC secretory processes, including glandular mucus secretion; and cellular antioxidants derived from lysis of RTECs and of inflammatory cells. The antioxidant composition of RTLFs and their role in modulating normal and pathophysiologic RTEC functions under conditions of oxidative stress are yet to be fully characterized. PMID:7705296

Pharmacotherapy for uveitis: current management and emerging therapy

PubMed Central

Barry, Robert J; Nguyen, Quan Dong; Lee, Richard W; Murray, Philip I; Denniston, Alastair K

2014-01-01

Uveitis, a group of conditions characterized by intraocular inflammation, is a major cause of sight loss in the working population. Most uveitis seen in Western countries is noninfectious and appears to be autoimmune or autoinflammatory in nature, requiring treatment with immunosuppressive and/or anti-inflammatory drugs. In this educational review, we outline the ideal characteristics of drugs for uveitis and review the data to support the use of current and emerging therapies in this context. It is crucial that we continue to develop new therapies for use in uveitis that aim to suppress disease activity, prevent accumulation of damage, and preserve visual function for patients with the minimum possible side effects. PMID:25284976

Macular pigmentation complicating irritant contact dermatitis and viral warts in Laugier-Hunziker syndrome.

PubMed

Bhoyrul, B; Paulus, J

2016-04-01

Laugier-Hunziker syndrome (LHS) is a rare acquired disorder characterized by macu-lar pigmentation of the lips and oral mucosa, with frequent longitudinal melanonychia. Involvement of other areas, such as the genitalia and fingers, has rarely been described. LHS is a benign condition with no known systemic manifestations. We report the case of a woman who developed melanotic macules on her fingers and elbow 16 years after the onset of pigmentation of her lips. This unusual feature of LHS in our patient was associated with irritant contact dermatitis and viral warts. Only two cases of an association with an inflammatory dermatosis have been reported previously in the literature. © 2015 British Association of Dermatologists.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults.

PubMed

Leitner, Gerda C; Vogelsang, Harald

2016-02-06

Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids.

Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults

PubMed Central

Leitner, Gerda C; Vogelsang, Harald

2016-01-01

Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn’s disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient’s disease. IBD may require immune-suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-α inhibitors or anti-integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5-aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro-inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8+ T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids. PMID:26855808

The Administration of Escherichia coli Nissle 1917 Ameliorates Development of DSS-Induced Colitis in Mice

PubMed Central

Rodríguez-Nogales, Alba; Algieri, Francesca; Garrido-Mesa, José; Vezza, Teresa; Utrilla, Maria P.; Chueca, Natalia; Fernández-Caballero, Jose A.; García, Federico; Rodríguez-Cabezas, Maria E.; Gálvez, Julio

2018-01-01

The beneficial effects of probiotics on immune-based pathologies such as inflammatory bowel disease (IBD) have been well reported. However, their exact mechanisms have not been fully elucidated. Few studies have focused on the impact of probiotics on the composition of the colonic microbiota. The aim of the present study was to correlate the intestinal anti-inflammatory activity of the probiotic Escherichia coli Nissle 1917 (EcN) in the dextran sodium sulfate (DSS) model of mouse colitis with the changes induced in colonic microbiota populations. EcN prevented the DSS-induced colonic damage, as evidenced by lower disease activity index (DAI) values and colonic weight/length ratio, when compared with untreated control mice. The beneficial effects were confirmed biochemically, since the probiotic treatment improved the colonic expression of different cytokines and proteins involved in epithelial integrity. In addition, it restored the expression of different micro-RNAs (miR-143, miR-150, miR-155, miR-223, and miR-375) involved in the inflammatory response that occurs in colitic mice. Finally, the characterization of the colonic microbiota by pyrosequencing showed that the probiotic administration was able to counteract the dysbiosis associated with the intestinal inflammatory process. This effect was evidenced by an increase in bacterial diversity in comparison with untreated colitic mice. The intestinal anti-inflammatory effects of the probiotic EcN were associated with an amelioration of the altered gut microbiome in mouse experimental colitis, especially when considering bacterial diversity, which is reduced in these intestinal conditions. Moreover, this probiotic has shown an ability to modulate expression levels of miRNAs and different mediators of the immune response involved in gut inflammation. This modulation could also be of great interest to understand the mechanism of action of this probiotic in the treatment of IBD.

13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis

PubMed Central

Walker, Mary E.; Souza, Patricia R.; Colas, Romain A.; Dalli, Jesmond

2017-01-01

Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins—atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)—to mice during inflammatory arthritis up-regulated systemic and tissue amounts of a novel family of proresolving mediators, termed 13-series resolvins (RvTs), and significantly reduced joint disease. Of note, administration of simvastatin (0.2 mg/kg) did not significantly up-regulate RvTs or reduce joint inflammation. We also found that atorvastatin and pravastatin each reduced systemic leukocyte activation, including platelet-monocyte aggregates (∼25–60%). These statins decreased neutrophil trafficking to the joint as well as joint monocyte and macrophage numbers. Atorvastatin and pravastatin produced significant reductions (∼30–50%) in expression of CD11b and major histocompatibility complex class II on both monocytes and monocyte-derived macrophages in joints. Administration of an inhibitor to cyclooxygenase-2, the initiating enzyme in the RvT pathway, reversed the protective actions of these statins on both joint and systemic inflammation. Together, these findings provide evidence for the role of RvTs in mediating the protective actions of atorvastatin and pravastatin in reducing local and vascular inflammation, and suggest that RvTs may be useful in measuring the anti-inflammatory actions of statins.—Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis. PMID:28465323

Accelerated hematopoietic syndrome after radiation doses bridging hematopoietic (H-ARS) and gastrointestinal (GI-ARS) acute radiation syndrome: early hematological changes and systemic inflammatory response syndrome in minipig.

PubMed

Moroni, Maria; Elliott, Thomas B; Deutz, Nicolaas E; Olsen, Cara H; Owens, Rossitsa; Christensen, Christine; Lombardini, Eric D; Whitnall, Mark H

2014-05-01

To characterize acute radiation syndrome (ARS) sequelae at doses intermediate between the bone marrow (H-ARS) and full gastrointestinal (GI-ARS) syndrome. Male minipigs, approximately 5 months old, 9-12 kg in weight, were irradiated with Cobalt-60 (total body, bilateral gamma irradiation, 0.6 Gy/min). Endpoints were 10-day survival, gastrointestinal histology, plasma citrulline, bacterial translocation, vomiting, diarrhea, vital signs, systemic inflammatory response syndrome (SIRS), febrile neutropenia (FN). We exposed animals to doses (2.2-5.0 Gy) above those causing H-ARS (1.6-2.0 Gy), and evaluated development of ARS. Compared to what was observed during H-ARS (historical data: Moroni et al. 2011a , 2011c ), doses above 2 Gy produced signs of increasingly severe pulmonary damage, faster deterioration of clinical conditions, and faster increases in levels of C-reactive protein (CRP). In the range of 4.6-5.0 Gy, animals died by day 9-10; signs of the classic GI syndrome, as measured by diarrhea, vomiting and bacterial translocation, did not occur. At doses above 2 Gy we observed transient reduction in circulating citrulline levels, and animals exhibited earlier depletion of blood elements and faster onset of SIRS and FN. An accelerated hematopoietic subsyndrome (AH-ARS) is observed at radiation doses between those producing H-ARS and GI-ARS. It is characterized by early onset of SIRS and FN, and greater lung damage, compared to H-ARS.

Effect of morphological and functional changes in the secundines on biometric parameters of newborns from dichorionic twin pregnancies.

PubMed

Waszak, Małgorzata; Cieślik, Krystyna; Pietryga, Marek; Lewandowski, Jacek; Chuchracki, Marek; Nowak-Markwitz, Ewa; Bręborowicz, Grzegorz

2016-01-01

The aim of the study was to determine if, and to what extent, structural and functional changes of the secundines influence biometric parameters of neonates from dichorionic twin pregnancies. The study included neonates from dichorionic, diamniotic twin pregnancies, along with their secundines. Based on histopathological examination of the secundines, the mass and dimensions of the placenta, length and condition of the umbilical cord, chorionicity, focal lesions, and microscopic placental abnormalities were determined for 445 pairs of twins. Morphological development of examined twins was characterized on the basis of their six somatic traits, while birth status of the newborns was assessed based on their Apgar scores. Statistical analysis included Student t-tests, Snedecor's F-tests, post-hoc tests, non-parametric chi-squared Pearson's tests, and determination of Spearman coefficients of rank correlation. The lowest values of analyzed somatic traits were observed in twins who had placentas with velamentous or marginal cord insertion. Inflammatory lesions in the placenta and placental abruption turned out to have the greatest impact of all analyzed abnormalities of the secundines. Inflammatory lesions in the placenta were associated with lower values of biometric parameters and a greater likelihood of preterm birth. Neonates with a history of placental abruption were characterized by significantly lower birth weight and smaller chest circumference. Morphological changes in the secundines have a limited impact on biometric parameters of neonates from dichorionic twin pregnancies. In turn, functional changes exert a significant effect and more often contribute to impaired fetal development.

Dermal fibroblast-to-myofibroblast transition sustained by αvß3 integrin-ILK-Snail1/Slug signaling is a common feature for hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders.

PubMed

Zoppi, Nicoletta; Chiarelli, Nicola; Binetti, Silvia; Ritelli, Marco; Colombi, Marina

2018-04-01

Hypermobile Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder with unknown molecular basis mainly characterized by generalized joint hypermobility, joint instability complications, and minor skin changes. The phenotypic spectrum is broad and includes multiple associated symptoms shared with chronic inflammatory systemic diseases. The stricter criteria defined in the 2017 EDS nosology leave without an identity many individuals with symptomatic joint hypermobility and/or features of hEDS; for these patients, the term Hypermobility Spectrum Disorders (HSD) was introduced. We previously reported that in vitro cultured hEDS and HSD patients' skin fibroblasts show a disarray of several extracellular matrix (ECM) components and dysregulated expression of genes involved in connective tissue homeostasis and inflammatory/pain/immune responses. Herein, we report that hEDS and HSD skin fibroblasts exhibit in vitro a similar myofibroblast-like phenotype characterized by the organization of α-smooth muscle actin cytoskeleton, expression of OB-cadherin/cadherin-11, enhanced migratory capability associated with augmented levels of the ECM-degrading metalloproteinase-9, and altered expression of the inflammation mediators CCN1/CYR61 and CCN2/CTGF. We demonstrate that in hEDS and HSD cells this fibroblast-to-myofibroblast transition is triggered by a signal transduction pathway that involves αvβ3 integrin-ILK complexes, organized in focal adhesions, and the Snail1/Slug transcription factor, thus providing insights into the molecular mechanisms related to the pathophysiology of these protean disorders. The indistinguishable phenotype identified in hEDS and HSD cells resembles an inflammatory-like condition, which correlates well with the systemic phenotype of patients, and suggests that these multisystemic disorders might be part of a phenotypic continuum rather than representing distinct clinical entities. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

PubMed

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Antibiotic and Anti-Inflammatory Therapies for Cystic Fibrosis

PubMed Central

Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart

2013-01-01

Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054

The BCL-2 family protein Bid is critical for pro-inflammatory signaling in astrocytes.

PubMed

König, Hans-Georg; Coughlan, Karen S; Kinsella, Sinéad; Breen, Bridget A; Prehn, Jochen H M

2014-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons in the spinal cord, brainstem and motor cortex. Mutations in the superoxide dismutase 1 (SOD1) gene represent a frequent genetic determinant and recapitulate a disease phenotype similar to ALS when expressed in mice. Previous studies using SOD1(G93A) transgenic mice have suggested a paracrine mechanism of neuronal loss, in which cytokines and other toxic factors released from astroglia or microglia trigger motoneuron degeneration. Several pro-inflammatory cytokines activate death receptors and may downstream from this activate the Bcl-2 family protein, Bid. We here sought to investigate the role of Bid in astrocyte activation and non-cell autonomous motoneuron degeneration. We found that spinal cord Bid protein levels increased significantly during disease progression in SOD1(G93A) mice. Subsequent experiments in vitro indicated that Bid was expressed at relatively low levels in motoneurons, but was enriched in astrocytes and microglia. Bid was strongly induced in astrocytes in response to pro-inflammatory cytokines or exposure to lipopolysaccharide. Experiments in bid-deficient astrocytes or astrocytes treated with a small molecule Bid inhibitor demonstrated that Bid was required for the efficient activation of transcription factor nuclear factor-κB in response to these pro-inflammatory stimuli. Finally, we found that conditioned medium from wild-type astrocytes, but not from bid-deficient astrocytes, was toxic when applied to primary motoneuron cultures. Collectively, our data demonstrate a new role for the Bcl-2 family protein Bid as a mediator of astrocyte activation during neuroinflammation, and suggest that Bid activation may contribute to non-cell autonomous motoneuron degeneration in ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice.

PubMed

Zeidler-Erdely, Patti C; Battelli, Lori A; Stone, Sam; Chen, Bean T; Frazer, David G; Young, Shih-Houng; Erdely, Aaron; Kashon, Michael L; Andrews, Ronnee; Antonini, James M

2011-02-01

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m(3)×3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.

γδ T Cells Regulate the Early Inflammatory Response to Bordetella pertussis Infection in the Murine Respiratory Tract

PubMed Central

Zachariadis, O.; Cassidy, J. P.; Brady, J.; Mahon, B. P.

2006-01-01

The role of γδ T cells in the regulation of pulmonary inflammation following Bordetella pertussis infection was investigated. Using a well-characterized murine aerosol challenge model, inflammatory events in mice with targeted disruption of the T-cell receptor δ-chain gene (γδ TCR−/− mice) were compared with those in wild-type animals. Early following challenge with B. pertussis, γδ TCR−/− mice exhibited greater pulmonary inflammation, as measured by intra-alveolar albumin leakage and lesion histomorphometry, yet had lower contemporaneous bacterial lung loads. The larger numbers of neutrophils and macrophages and the greater concentration of the neutrophil marker myeloperoxidase in bronchoalveolar lavage fluid from γδ TCR−/− mice at this time suggested that differences in lung injury were mediated through increased leukocyte trafficking into infected alveoli. Furthermore, flow cytometric analysis found the pattern of recruitment of natural killer (NK) and NK receptor+ T cells into airspaces differed between the two mouse types over the same time period. Taken together, these findings suggest a regulatory influence for γδ T cells over the early pulmonary inflammatory response to bacterial infection. The absence of γδ T cells also influenced the subsequent adaptive immune response to specific bacterial components, as evidenced by a shift from a Th1 to a Th2 type response against the B. pertussis virulence factor filamentous hemagglutinin in γδ TCR−/− mice. The findings are relevant to the study of conditions such as neonatal B. pertussis infection and acute respiratory distress syndrome where γδ T cell dysfunction has been implicated in the inflammatory process. PMID:16495558

A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype.

PubMed

Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf

2015-11-24

DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance.

Suppression of pro-inflammatory T-cell responses by human mesothelial cells.

PubMed

Lin, Chan-Yu; Kift-Morgan, Ann; Moser, Bernhard; Topley, Nicholas; Eberl, Matthias

2013-07-01

Human γδ T cells reactive to the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP) contribute to acute inflammatory responses. We have previously shown that peritoneal dialysis (PD)-associated infections with HMB-PP producing bacteria are characterized by locally elevated γδ T-cell frequencies and poorer clinical outcome compared with HMB-PP negative infections, implying that γδ T cells may be of diagnostic, prognostic and therapeutic value in acute disease. The regulation by local tissue cells of these potentially detrimental γδ T-cell responses remains to be investigated. Freshly isolated γδ or αβ T cells were cultured with primary mesothelial cells derived from omental tissue, or with mesothelial cell-conditioned medium. Stimulation of cytokine production and proliferation by peripheral T cells in response to HMB-PP or CD3/CD28 beads was assessed by flow cytometry. Resting mesothelial cells were potent suppressors of pro-inflammatory γδ T cells as well as CD4+ and CD8+ αβ T cells. The suppression of γδ T-cell responses was mediated through soluble factors released by primary mesothelial cells and could be counteracted by SB-431542, a selective inhibitor of TGF-β and activin signalling. Recombinant TGF-β1 but not activin-A mimicked the mesothelial cell-mediated suppression of γδ T-cell responses to HMB-PP. The present findings indicate an important regulatory function of mesothelial cells in the peritoneal cavity by dampening pro-inflammatory T-cell responses, which may help preserve the tissue integrity of the peritoneal membrane in the steady state and possibly during the resolution of acute inflammation.

TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

PubMed Central

Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

2013-01-01

Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

A multi-stage process including transient polyploidization and EMT precedes the emergence of chemoresistent ovarian carcinoma cells with a dedifferentiated and pro-inflammatory secretory phenotype

PubMed Central

Rohnalter, Verena; Roth, Katrin; Finkernagel, Florian; Adhikary, Till; Obert, Julia; Dorzweiler, Kristina; Bensberg, Maike; Müller-Brüsselbach, Sabine; Müller, Rolf

2015-01-01

DNA-damaging drugs induce a plethora of molecular and cellular alterations in tumor cells, but their interrelationship is largely obscure. Here, we show that carboplatin treatment of human ovarian carcinoma SKOV3 cells triggers an ordered sequence of events, which precedes the emergence of mitotic chemoresistant cells. The initial phase of cell death after initiation of carboplatin treatment is followed around day 14 by the emergence of a mixed cell population consisting of cycling, cell cycle-arrested and senescent cells. At this stage, giant cells make up >80% of the cell population, p21 (CDKN1A) in strongly induced, and cell numbers remain nearly static. Subsequently, cell death decreases, p21 expression drops to a low level and cell divisions increase, including regular mitoses of giant cells and depolyploidization by multi-daughter divisions. These events are accompanied by the upregulation of stemness markers and a pro-inflammatory secretory phenotype, peaking after approximately 14 days of treatment. At the same time the cells initiate epithelial to mesenchymal transition, which over the subsequent weeks continuously increases, concomitantly with the emergence of highly proliferative, migratory, dedifferentiated, pro-inflammatory and chemoresistant cells (SKOV3-R). These cells are anchorage-independent and grow in a 3D collagen matrix, while cells on day 14 do not survive under these conditions, indicating that SKOV3-R cells were generated thereafter by the multi-stage process described above. This process was essentially recapitulated with the ovarian carcinoma cell line IGROV-1. Our observations suggest that transitory cells characterized by polyploidy, features of stemness and a pro-inflammatory secretory phenotype contribute to the acquisition of chemoresistance. PMID:26503466

Comprehensive evaluation of poly(I:C) induced inflammatory response in an airway epithelial model

PubMed Central

Lever, Amanda R; Park, Hyoungshin; Mulhern, Thomas J; Jackson, George R; Comolli, James C; Borenstein, Jeffrey T; Hayden, Patrick J; Prantil-Baun, Rachelle

2015-01-01

Respiratory viruses invade the upper airway of the lung, triggering a potent immune response that often exacerbates preexisting conditions such as asthma and COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the characteristic inflammatory response associated with viral infection, such as loss of epithelial integrity, and increased production of mucus and inflammatory cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well-defined primary normal human bronchial epithelial (NHBE) model that recapitulates in vivo functions and responses. We developed functional and quantifiable methods to evaluate the physiology of our model in both healthy and inflamed states. Through gene and protein expression, we validated the differentiation state and population of essential cell subtypes (i.e., ciliated, goblet, club, and basal cells) as compared to the human lung. Assays for total mucus production, cytokine secretion, and barrier function were used to evaluate in vitro physiology and response to viral insult. Cells were treated apically with poly(I:C) and evaluated 48 h after induction. Results revealed a dose-dependent increase in goblet cell differentiation, as well as, an increase in mucus production relative to controls. There was also a dose-dependent increase in secretion of IL-6, IL-8, TNF-α, and RANTES. Epithelial barrier function, as measured by TEER, was maintained at 1501 ± 355 Ω*cm² postdifferentiation, but dropped significantly when challenged with poly(I:C). This study provides first steps toward a well-characterized model with defined functional methods for understanding dsRNA stimulated inflammatory responses in a physiologically relevant manner. PMID:25847914

Acrylamide-induced oxidative stress and inflammatory response are alleviated by N-acetylcysteine in PC12 cells: Involvement of the crosstalk between Nrf2 and NF-κB pathways regulated by MAPKs.

PubMed

Pan, Xiaoqi; Wu, Xu; Yan, Dandan; Peng, Cheng; Rao, Chaolong; Yan, Hong

2018-05-15

Acrylamide (ACR) is a classic neurotoxin in animals and humans. However, the mechanism underlying ACR neurotoxicity remains controversial, and effective prevention and treatment measures against this condition are scarce. This study focused on clarifying the crosstalk between the involved signaling pathways in ACR-induced oxidative stress and inflammatory response and investigating the protective effect of antioxidant N-acetylcysteine (NAC) against ACR in PC12 cells. Results revealed that ACR exposure led to oxidative stress characterized by significant increase in reactive oxygen species (ROS) and malondialdehyde (MDA) levels and glutathione (GSH) consumption. Inflammatory response was observed based on the dose-dependently increased levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). NAC attenuated ACR-induced enhancement of MDA and ROS levels and TNF-α generation. In addition, ACR activated nuclear transcription factor E2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB) signaling pathways. Knockdown of Nrf2 by siRNA significantly blocked the increased NF-κB p65 protein expression in ACR-treated PC12 cells. Down-regulation of NF-κB by specific inhibitor BAY11-7082 similarly reduced ACR-induced increase in Nrf2 protein expression. NAC treatment increased Nrf2 expression and suppressed NF-κB p65 expression to ameliorate oxidative stress and inflammatory response caused by ACR. Further results showed that mitogen-activated protein kinases (MAPKs) pathway was activated prior to the activation of Nrf2 and NF-κB pathways. Inhibition of MAPKs blocked Nrf2 and NF-κB pathways. Collectively, ACR activated Nrf2 and NF-κB pathways which were regulated by MAPKs. A crosstalk between Nrf2 and NF-κB pathways existed in ACR-induced cell damage. NAC protected against oxidative damage and inflammatory response induced by ACR by activating Nrf2 and inhibiting NF-κB pathways in PC12 cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Multifactorial Experimental Design to Optimize the Anti-Inflammatory and Proangiogenic Potential of Mesenchymal Stem Cell Spheroids.

PubMed

Murphy, Kaitlin C; Whitehead, Jacklyn; Falahee, Patrick C; Zhou, Dejie; Simon, Scott I; Leach, J Kent

2017-06-01

Mesenchymal stem cell therapies promote wound healing by manipulating the local environment to enhance the function of host cells. Aggregation of mesenchymal stem cells (MSCs) into three-dimensional spheroids increases cell survival and augments their anti-inflammatory and proangiogenic potential, yet there is no consensus on the preferred conditions for maximizing spheroid function in this application. The objective of this study was to optimize conditions for forming MSC spheroids that simultaneously enhance their anti-inflammatory and proangiogenic nature. We applied a design of experiments (DOE) approach to determine the interaction between three input variables (number of cells per spheroid, oxygen tension, and inflammatory stimulus) on MSC spheroids by quantifying secretion of prostaglandin E 2 (PGE 2 ) and vascular endothelial growth factor (VEGF), two potent molecules in the MSC secretome. DOE results revealed that MSC spheroids formed with 40,000 cells per spheroid in 1% oxygen with an inflammatory stimulus (Spheroid 1) would exhibit enhanced PGE 2 and VEGF production versus those formed with 10,000 cells per spheroid in 21% oxygen with no inflammatory stimulus (Spheroid 2). Compared to Spheroid 2, Spheroid 1 produced fivefold more PGE 2 and fourfold more VEGF, providing the opportunity to simultaneously upregulate the secretion of these factors from the same spheroid. The spheroids induced macrophage polarization, sprout formation with endothelial cells, and keratinocyte migration in a human skin equivalent model-demonstrating efficacy on three key cell types that are dysfunctional in chronic non-healing wounds. We conclude that DOE-based analysis effectively identifies optimal culture conditions to enhance the anti-inflammatory and proangiogenic potential of MSC spheroids. Stem Cells 2017;35:1493-1504. © 2017 AlphaMed Press.

Bakery flour dust exposure causes non-allergic inflammation and enhances allergic airway inflammation in mice

PubMed Central

Marraccini, Paolo; Brass, David M.; Hollingsworth, John W.; Maruoka, Shuichiro; Garantziotis, Stavros; Schwartz, David A.

2014-01-01

Background Baker’s asthma is one of the most commonly reported occupational lung diseases in countries where fresh bread is baked daily in large quantities, and is characterized by rhinitis, bronchial hyperresponsiveness, and reversible airflow obstruction. Epidemiological studies have identified pre-existing atopy as an important risk factor for developing baker’s asthma, yet the etiology and pathogenesis of baker’s asthma remain poorly understood. Objective We sought to develop a mouse model of baker’s asthma that could be used to characterize the development and progression of baker’s asthma. Methods We were unable to sensitize mice to bakery flour dust or flour dust extract. We assessed total inflammatory cells, cellular differential, total serum IgE and the pro-inflammatory cytokine response to oropharyngeally instilled bakery flour dust or flour dust extract by itself or in the context of OVA sensitization and challenge. Results Both bakery flour dust and flour dust extract consistently elicited a neutrophilic inflammation in a tlr4-independent manner; suggesting that endotoxin is not playing a role in the inflammatory response to flour dust. Moreover, bakery flour dust and dust extract significantly enhance the inflammatory response in OVA sensitized and challenged mice. Conclusions Bakery flour dust and flour dust extract are strongly pro-inflammatory and can cause non-allergic airway inflammation and can enhance allergen-mediated airway inflammation. PMID:18564331

Perna canaliculus and the Intestinal Microbiome.

PubMed

Saltzman, Emma Tali; Thomsen, Michael; Hall, Sean; Vitetta, Luis

2017-06-30

Natural medicines are often an attractive option for patients diagnosed with chronic conditions. Three main classes of bioactives that have been reported from marine mussel extracts include proteins, lipids and carbohydrates. Commercially, the most relevant species of marine mollusks belong to two genera, Perna and Mytilus. Specifically, the Perna canaliculus species has been repeatedly demonstrated to harbor anti-inflammatory compounds such as omega-3 polyunsaturated fatty acids ( ω -3 PUFAs) that can ameliorate pro-inflammatory conditions, or proteins that can promote thrombin inhibitory activity. Recent clinical studies have posited that extracts from green-lipped mussels may lead to prebiotic activity in the intestinal microbiome that in turn has been reported to improve symptoms of osteoarthritis of the knee. Prebiotics have been reported to favorably interact with the intestinal microbiome through the proliferation of beneficial bacteria in the gut, suppressing exogenous and endogenous intestinal infections and promoting homeostasis by balancing local pro- and anti-inflammatory actions. Bioactive compounds from Perna canaliculus are functional foods and, in this regard, may positively interact with the intestinal microbiome and provide novel therapeutic solutions for intra-intestinal and extra-intestinal inflammatory conditions.

Evaluation of acute pelvic pain in women.

PubMed

Kruszka, Paul S; Kruszka, Stephen J

2010-07-15

Diagnosis of pelvic pain in women can be challenging because many symptoms and signs are insensitive and nonspecific. As the first priority, urgent life-threatening conditions (e.g., ectopic pregnancy, appendicitis, ruptured ovarian cyst) and fertility-threatening conditions (e.g., pelvic inflammatory disease, ovarian torsion) must be considered. A careful history focusing on pain characteristics, review of systems, and gynecologic, sexual, and social history, in addition to physical examination helps narrow the differential diagnosis. The most common urgent causes of pelvic pain are pelvic inflammatory disease, ruptured ovarian cyst, and appendicitis; however, many other diagnoses in the differential may mimic these conditions, and imaging is often needed. Transvaginal ultrasonography should be the initial imaging test because of its sensitivities across most etiologies and its lack of radiation exposure. A high index of suspicion should be maintained for pelvic inflammatory disease when other etiologies are ruled out, because the presentation is variable and the prevalence is high. Multiple studies have shown that 20 to 50 percent of women presenting with pelvic pain have pelvic inflammatory disease. Adolescents and pregnant and postpartum women require unique considerations.

Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q'eqchi' Maya traditional medicine.

PubMed

Walshe-Roussel, Brendan; Choueiri, Christine; Saleem, Ammar; Asim, Muhammd; Caal, Federico; Cal, Victor; Rojas, Marco Otarola; Pesek, Todd; Durst, Tony; Arnason, John Thor

2013-08-01

The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q'eqchi' Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotanical investigation of the uses of N. lobata by the Q'eqchi' Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiterpene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 μg/mL reduced LPS-stimulated TNF-α production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Isolated sesquiterpene lactones, neurolenins B, C+D, lobatin B and 9α-hydroxy-8β-isovalerianyloxy-calyculatolide were more active (IC50=0.17-2.32 μM) than the positive control parthenolide (IC50=4.79 μM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

78 FR 46356 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... gout, arthritis, and cholesterol-associated atherosclerosis. The technology relates to arsenical... variety of inflammatory conditions. Potential Commercial Applications: Therapeutics for rheumatoid arthritis, gout, colitis and various inflammatory skin diseases. Competitive Advantages: These FDA-approved...

Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.

PubMed

Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

2016-04-01

Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ(+)RORγt(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Anti-inflammatory activities and glycerophospholipids metabolism in KLA-stimulated RAW 264.7 macrophage cells by diarylheptanoids from the rhizomes of Alpinia officinarum.

PubMed

Zhang, Guogai; Zhao, Lifang; Zhu, Jiancheng; Feng, Yifan; Wu, Xia

2018-02-01

Alpinia officinarum is used for its anti-inflammatory activity historically in China. Diarylheptanoids isolated from A. officinarum play important biological roles in the prevention and treatment of inflammatory disorders. Seven diarylheptanoids (1-7) were isolated from A. officinarum. The cell viabilities and anti-inflammatory activities of diarylheptanoids were evaluated by MTT assay and tumor necrosis factor-α production in Kdo2-lipid A-stimulated RAW 264.7 cells in vitro. The relationships between their anti-inflammatories and structure-activities are discussed. The results indicated that compounds 1 and 3-7 had significant anti-inflammatory activities. The relationships between inflammation and phospholipids metabolism were elucidated by multivariate data analysis. Twenty-two potential biomarkers were identified in inflammatory group vs. blank group, and 11 potential biomarkers were identified for inflammatory group vs. drug-treatment groups. Ten common phospholipids were characterized. On the basis of a previous study in our laboratory, we found that phosphatidylethanolamine (18:0/18:1) might be the important glycerophospholipid biomarker in inflammation. In this study, we firstly combined anti-inflammatory activities and glycerophospholipids changes of traditional Chinese medicine. This work suggests that the anti-inflammatory activities of diarylheptanoids might be significantly related to glycerophospholipids and could provide a useful database for investigating the anti-inflammatory effects of traditional Chinese medicine. Copyright © 2017 John Wiley & Sons, Ltd.

Development of Non-Hormonal Steroids for the Treatment of Duchenne Muscular Dystrophy

DTIC Science & Technology

2013-02-01

rat models of irritant contact dermatitis and allergic contact dermatitis showed that this compound exerted potent anti- inflammatory activity...conditions such as arthriti dermatitis , asthma, muscular dystrophy, and auto-immune disor ders.20–22 However, glucocorticoids have many off-target effect...commonly pre- scribed drugs due to their potent anti-inflammatory properties, and remain standard of care in many conditions such as arthritis, dermatitis

Inhibition of Prostaglandin E2 Production by Anti-inflammatory Hypericum perforatum Extracts and Constituents in RAW264.7 Mouse Macrophage Cells

PubMed Central

Hammer, Kimberly D. P.; Hillwig, Matthew L.; Solco, Avery K. S.; Dixon, Philip M.; Delate, Kathleen; Murphy, Patricia A.; Wurtele, Eve S.; Birt, Diane F.

2008-01-01

Hypericum perforatum (Hp) is commonly known for its antiviral, antidepressant, and cytotoxic properties, but traditionally Hp was also used to treat inflammation. In this study, the anti-inflammatory activity and cytotoxicity of different Hp extractions and accessions and constituents present within Hp extracts were characterized. In contrast to the antiviral activity of Hp, the anti-inflammatory activity observed with all Hp extracts was light-independent. When pure constituents were tested, the flavonoids, amentoflavone, hyperforin, and light-activated pseudohypericin, displayed anti-inflammatory activity, albeit at concentrations generally higher than the amount present in the Hp extracts. Constituents that were present in the Hp extracts at concentrations that inhibited the production of prostaglandin E2 (PGE2) were pseudohypericin and hyperforin, suggesting that they are the primary anti-inflammatory constituents along with the flavonoids, and perhaps the interactions of these constituents and other unidentified compounds are important for the anti-inflammatory activity of the Hp extracts. PMID:17696442

Inflammatory signaling in human Tuberculosis granulomas is spatially organized

PubMed Central

Marakalala, Mohlopheni J.; Raju, Ravikiran M.; Sharma, Kirti; Zhang, Yanjia J.; Eugenin, Eliseo A.; Prideaux, Brendan; Daudelin, Isaac B.; Chen, Pei-Yu; Booty, Matthew G.; Kim, Jin Hee; Eum, Seok Yong; Via, Laura E.; Behar, Samuel M.; Barry, Clifton E.; Mann, Matthias; Dartois, Véronique; Rubin, Eric J.

2016-01-01

Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased fashion. Using laser capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas. We found that the centers of granulomas possess a pro-inflammatory environment characterized by anti-microbial peptides, ROS and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum possesses a comparatively anti-inflammatory signature. These findings are consistent across a set of six subjects and in rabbits. While the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma. The protein and lipid snapshots of human and rabbit lesions analysed here suggest that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma. PMID:27043495

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

PubMed

Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

Flavocoxid, a Nutraceutical Approach to Blunt Inflammatory Conditions

PubMed Central

Squadrito, Francesco; Mecchio, Anna

2014-01-01

Flavonoids, from Scutellaria baicalensis (Chinese skullcap) and Acacia catechu (black catechu), have been shown to exert a variety of therapeutic effects, including anti-inflammatory, antiviral, antibacterial, and anticancer activities. Flavocoxid is a mixed extract containing baicalin and catechin and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Controlled clinical trials and a postmarketing study have clearly shown that flavocoxid is as effective as naproxen in managing the signs and symptoms of osteoarthritis of the knee and it has better upper gastrointestinal, renal, and respiratory safety profile than naproxen. Flavocoxid may therefore provide a potential therapeutic approach to the treatment of chronic inflammatory conditions. PMID:25242871

Flavocoxid, a nutraceutical approach to blunt inflammatory conditions.

PubMed

Bitto, Alessandra; Squadrito, Francesco; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Mecchio, Anna; Galfo, Federica; Altavilla, Domenica

2014-01-01

Flavonoids, from Scutellaria baicalensis (Chinese skullcap) and Acacia catechu (black catechu), have been shown to exert a variety of therapeutic effects, including anti-inflammatory, antiviral, antibacterial, and anticancer activities. Flavocoxid is a mixed extract containing baicalin and catechin and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Controlled clinical trials and a postmarketing study have clearly shown that flavocoxid is as effective as naproxen in managing the signs and symptoms of osteoarthritis of the knee and it has better upper gastrointestinal, renal, and respiratory safety profile than naproxen. Flavocoxid may therefore provide a potential therapeutic approach to the treatment of chronic inflammatory conditions.

The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells.

PubMed

Machado-Santos, Joana; Saji, Etsuji; Tröscher, Anna R; Paunovic, Manuela; Liblau, Roland; Gabriely, Galina; Bien, Christian G; Bauer, Jan; Lassmann, Hans

2018-06-04

Multiple sclerosis is an inflammatory demyelinating disease in which active demyelination and neurodegeneration are associated with lymphocyte infiltrates in the brain. However, so far little is known regarding the phenotype and function of these infiltrating lymphocyte populations. In this study, we performed an in-depth phenotypic characterization of T and B cell infiltrates in a large set of multiple sclerosis cases with different disease and lesion stages and compared the findings with those seen in inflammatory, non-inflammatory and normal human controls. In multiple sclerosis lesions, we found a dominance of CD8+ T cells and a prominent contribution of CD20+ B cells in all disease courses and lesion stages, including acute multiple sclerosis cases with very short disease duration, while CD4+ T cells were sparse. A dominance of CD8+ T cells was also seen in other inflammatory controls, such as Rasmussen's encephalitis and viral encephalitis, but the contribution of B cells in these diseases was modest. Phenotypic analysis of the CD8+ T cells suggested that part of the infiltrating cells in active lesions proliferate, show an activated cytotoxic phenotype and are in part destroyed by apoptosis. Further characterization of the remaining cells suggest that CD8+ T cells acquire features of tissue-resident memory cells, which may be focally reactivated in active lesions of acute, relapsing and progressive multiple sclerosis, while B cells, at least in part, gradually transform into plasma cells. The loss of surface molecules involved in the egress of leucocytes from inflamed tissue, such as S1P1 or CCR7, and the upregulation of CD103 expression may be responsible for the compartmentalization of the inflammatory response in established lesions. Similar phenotypic changes of tissue-infiltrating CD8+ T cells were also seen in Rasmussen's encephalitis. Our data underline the potential importance of CD8+ T lymphocytes and B cells in the inflammatory response in established multiple sclerosis lesions. Tissue-resident T and B cells may represent guardians of previous inflammatory brain disease, which can be reactivated and sustain the inflammatory response, when they are re-exposed to their specific antigen.

[Coexistence of coeliac disease and inflammatory bowel disease in children].

PubMed

Krawiec, Paulina; Pawłowska-Kamieniak, Agnieszka; Pac-Kożuchowska, Elżbieta; Mroczkowska-Juchkiewcz, Agnieszka; Kominek, Katarzyna

2016-01-01

Coeliac disease and inflammatory bowel disease are chronic inflammatory conditions of gastrointestinal tract with complex aetiology with genetic, environmental and immunological factors contributing to its pathogenesis. It was noted that immune-mediated disorders often coexist. There is well-known association between coeliac disease and type 1 diabetes and ulcerative colitis and primary sclerosing cholangitis. However, growing body of literature suggests the association between coeliac disease and inflammatory bowel disease, particularly ulcerative colitis. This is an extremely rare problem in paediatric gastroenterology. To date there have been reported several cases of children with coexisting coeliac disease and inflammatory bowel disease. Herewith we present review of current literature on coexistence of coeliac disease and inflammatory bowel disease in children. © 2016 MEDPRESS.

Sleep and inflammatory markers in different psychiatric disorders.

PubMed

Krysta, Krzysztof; Krzystanek, Marek; Bratek, Agnieszka; Krupka-Matuszczyk, Irena

2017-02-01

Many psychiatric disorders, like schizophrenia, affective disorders, addictions and different forms of dementia are associated with sleep disturbances. In the etiology and course of those diseases inflammatory processes are regarded to be an increasingly important factor. They are also a frequently discussed element of the pathology of sleep. In this literature review reports on correlations between poor sleep and inflammatory responses in various psychiatric conditions are discussed. The link between schizophrenia, affective disorders and inflammatory cytokines is a complex phenomenon, which has been already confirmed in a number of studies. However, the presence of sleep deficits in those conditions, being a common symptom of depression and psychoses, can be an additional factor having a considerable impact on the immunological processes in mental illnesses. In the analyzed data, a number of studies are presented describing the role of inflammatory markers in sleep disturbances and psychopathological symptoms of affective, psychotic, neurogenerative and other disorders. Also attention is drawn to possible implications for their treatment. Efforts to use, e.g., anti-inflammatory agents in psychiatry in the context of their impact on sleep are reported. The aspect of inflammatory markers in the role of sleep deprivation as the treatment method in major depressive disorder is also discussed. A general conclusion is drawn that the improvement of sleep quality plays a crucial role in the care for psychiatric patients.

Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: review of the available pre-clinical data, and first human studies.

PubMed

Darmani, Nissar A; Izzo, Angelo A; Degenhardt, Brian; Valenti, Marta; Scaglione, Giuseppe; Capasso, Raffaele; Sorrentini, Italo; Di Marzo, Vincenzo

2005-06-01

The endogenous cannabimimetic compound, and anandamide analogue, N-palmitoyl-ethanolamine (PEA), was shown to exert potent anti-inflammatory and analgesic effects in experimental models of visceral, neuropathic and inflammatory pain by acting via several possible mechanisms. However, only scant data have been reported on the regulation of PEA levels during pathological conditions in animals or, particularly, humans. We review the current literature on PEA and report the results of three separate studies indicating that its concentrations are significantly increased during three different inflammatory and neuropathic conditions, two of which have been assessed in humans, and one in a mouse model. In patients affected with chronic low back pain, blood PEA levels were not significantly different from those of healthy volunteers, but were significantly and differentially increased (1.6-fold, P<0.01, N=10 per group) 30 min following an osteopathic manipulative treatment. In the second study, the paw skin levels of PEA in mice with streptozotocin-induced diabetic neuropathic pain were found to be significantly higher (1.5-fold, P<0.005, N=5) than those of control mice. In the third study, colonic PEA levels in biopsies from patients with ulcerative colitis were found to be 1.8-fold higher (P<0.05, N=8-10) than those in healthy subjects. These heterogeneous data, together with previous findings reviewed here, substantiate the hypothesis that PEA is an endogenous mediator whose levels are increased following neuroinflammatory or neuropathic conditions in both animals and humans, possibly to exert a local anti-inflammatory and analgesic action.

Enhancement of anti-inflammatory activity of bromelain by its encapsulation in katira gum nanoparticles.

PubMed

Bernela, Manju; Ahuja, Munish; Thakur, Rajesh

2016-06-05

Bromelain-loaded katira gum nanoparticles were synthesized using 3 level optimization process and desirability approach. Nanoparticles of the optimized batch were characterized using particle size analysis, zeta potential, transmission electron microscopy and Fourier-transform infrared spectroscopy. Investigation of their in vivo anti-inflammatory activity by employing carrageenan induced rat-paw oedema method showed that encapsulation of bromelain in katira gum nanoparticles substantially enhanced its anti-inflammatory potential. This may be attributed to enhanced absorption owing to reduced particle size or to protection of bromelain from acid proteases. Copyright © 2016 Elsevier Ltd. All rights reserved.

TNF-alpha antagonist induced lupus on three different agents.

PubMed

Mudduluru, Bindu Madhavi; Shah, Shalin; Shamah, Steven; Swaminath, Arun

2017-03-01

Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis. We present a case of a 28-year-old female with Crohn's disease, who developed disabling arthritis as a clinical manifestation of ATIL following treatment with three anti-TNF agents, namely infliximab, adalimumab and certolizumab.

Helminthic therapy: improving mucosal barrier function

PubMed Central

Wolff, Martin J.; Broadhurst, Mara J.

2014-01-01

The epidemiology of autoimmune diseases and helminth infections led to suggestions that helminths could improve inflammatory conditions, which was then tested using animal models. This has translated to clinical investigations aimed at the safe and controlled reintroduction of helminthic exposure to patients suffering from autoimmune diseases (so-called “helminthic therapy”) in an effort to mitigate the inflammatory response. In this review, we will summarize the results of recent clinical trials of helminthic therapy, with particular attention to mechanisms of action. Whereas previous reviews have emphasized immune regulatory mechanisms activated by helminths, we propose that enhancement of mucosal barrier function may have an equally important role in improving conditions of inflammatory bowel diseases. PMID:22464690

Role of inflammation in the aging bones.

PubMed

Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

2015-02-15

Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging. Copyright © 2014 Elsevier Inc. All rights reserved.

Purification and function of two analgesic and anti-inflammatory peptides from coelomic fluid of the earthworm, Eisenia foetida.

PubMed

Li, Chunlong; Chen, Mengrou; Li, Xiaojie; Yang, Meifeng; Wang, Ying; Yang, Xinwang

2017-03-01

The potential application of anti-inflammatory and analgesic compounds in medication and therapeutic care have become of increasing interest. We purified and characterized two novel analgesic and anti-inflammatory peptides, VQ-5 and AQ-5, from the coelomic fluid of the earthworm (Eisenia foetida). Their primary structures were determined as VSSVQ and AMADQ, respectively. Both peptides, especially AQ-5, exhibited analgesic activity in mouse models of persistent neuropathic pain and inflammation. AQ-5 also inhibited tumor necrosis factor alpha and cyclooxygenase-2 production. The mitogen-activated protein kinase signaling pathway, which is involved in analgesic and anti-inflammatory functions, was inhibited by AQ-5. Thus, the analgesic and anti-inflammatory effects of these peptides, especially AQ-5, demonstrated their potential as candidates for the development of novel analgesic medicines. Copyright © 2017 Elsevier Inc. All rights reserved.

Antinociceptive and anti-inflammatory activities of a pomegranate (Punica granatum L.) extract rich in ellagitannins.

PubMed

González-Trujano, María Eva; Pellicer, Francisco; Mena, Pedro; Moreno, Diego A; García-Viguera, Cristina

2015-01-01

Pomegranate (Punica granatum L.) has been used for centuries for the treatment of inflammatory diseases. However, there is a lack of comprehensive information focused on the properties of a certain pomegranate (poly)phenolic profile to cure pain and gastric injury induced by anti-inflammatory drugs. This study investigated the systemic effects of different doses of a HPLC-characterized pomegranate extract on the formalin-induced nociceptive behavior in mice. The effect of the extract against gastric injury caused by non-steroidal anti-inflammatory drugs and ethanol was also assessed. Pomegranate reduced nociception in both phases of the formalin test, suggesting central and peripheral activities to inhibit nociception. Indomethacin-induced gastric injury was not produced in the presence of pomegranate, which also protected against ethanol-induced gastric lesions. The present results reinforce the benefits of pomegranate (poly)phenolics in the treatment of pain as well as their anti-inflammatory properties.

Trauma-induced systemic inflammatory response versus exercise-induced immunomodulatory effects.

PubMed

Fehrenbach, Elvira; Schneider, Marion E

2006-01-01

Accidental trauma and heavy endurance exercise, both induce a kind of systemic inflammatory response, also called systemic inflammatory response syndrome (SIRS). Exercise-related SIRS is conditioned by hyperthermia and concomitant heat shock responses, whereas trauma-induced SIRS manifests concomitantly with tissue necrosis and immune activation, secondarily followed by fever. Inflammatory cytokines are common denominators in both trauma and exercise, although there are marked quantitative differences. Different anti-inflammatory cytokines may be involved in the control of inflammation in trauma- and exercise-induced stress. Exercise leads to a balanced equilibrium between inflammatory and anti-inflammatory responses. Intermittent states of rest, as well as anti-oxidant capacity, are lacking or minor in trauma but are high in exercising individuals. Regular training may enhance immune competence, whereas trauma-induced SIRS often paves the way for infectious complications, such as sepsis.

Pathogenesis and Prediction of Future Rheumatoid Arthritis

DTIC Science & Technology

2014-10-01

characterized by abnormalities of the immune system prior to the onset of the clinically apparent inflammatory joint disease that currently defines RA. The...the clinically apparent inflammatory joint disease that currently defines RA. The primary goal of this project is to investigate this preclinical...environmental exposures such as smoking, periodontal disease were ascertained. Goal 2. Local and governmental IRB approvals, and HRPO approval, were obtained

Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

PubMed

Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

2014-06-15

Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes. Copyright © 2014 Elsevier B.V. All rights reserved.

FBXW7 protein has dual-role as tumor suppressor and inflammatory pathway inhibitor | Center for Cancer Research

Cancer.gov

Toll-like receptors (TLRs) are largely responsible for inducing innate immune responses to infection. TLR4 binds lipopolysaccharide (LPS) from Gram-negative bacteria and initiates a signaling pathway to activate inflammatory responses. TLR4 plays a role in diseases such as sepsis and chronic inflammatory disorders. In tumor cells, TLR4 is involved in dampening immune surveillance, and increasing proliferation, inflammatory cytokine production, and invasive migration. Determining how TLR4 expression and signaling is regulated may enable these adverse conditions to be better managed.

Overlapping gene expression profiles indicative of antigen processing and the interferon pathway characterize inflammatory fibrotic skin diseases.

PubMed

Limpers, Annelies; van Royen-Kerkhof, Annet; van Roon, Joel A G; Radstake, Timothy R D J; Broen, Jasper C A

2014-02-01

Inflammatory fibrotic disorders have been of high interest both for dermatologists and rheumatologists. Although the phenotypic end stage of this group of diseases is ultimately the same, namely fibrosis, patients present with different clinical features and are often treated with distinct therapeutic modalities. This review addresses whether there is evidence for different underlying molecular pathways in the various inflammatory fibrotic diseases such as localized scleroderma, pediatric lichen sclerosus, adult lichen sclerosus, eosinophilic fasciitis and systemic sclerosis. To investigate this, a large number of gene expression microarray studies performed on skin or fibroblasts from patients with these aforementioned diseases were described, (re-)analysed, and compared. As suspected by the heterogeneous phenotype, most diseases showed unique gene expression features. Intriguingly, a clear overlap was observed between adult and pediatric lichen sclerosus and localized scleroderma, in antigen processing and the interferon pathway. Delineating the cause and consequence of these pathways may generate novel tools to better characterize and more effectively treat these patients.

Inflammation, chronic obstructive pulmonary disease and aging.

PubMed

Provinciali, Mauro; Cardelli, Maurizio; Marchegiani, Francesca

2011-12-01

Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal persistent inflammatory response to noxious environmental stimuli, particularly cigarette smoke. The determinants of the dysregulated immune responses, which play a role both in the onset and continuation of COPD, are largely unknown. We examined several molecular mechanisms regulating the inflammatory pathway, such as cytokine polymorphisms, miRNA expression, and DNA methylation in COPD and aging, with the aim to provide evidence supporting the view that aging of the immune system may predispose to COPD. The incidence of COPD increases with age. The pathogenesis of the disease is linked to a chronic inflammation and involves the recruitment and regulation of innate and adaptive immune cells. A chronic systemic inflammation characterizes aging and has been correlated with many diseases, most of them age-related. COPD and aging are associated with significant dysregulation of the immune system that leads to a chronic inflammatory response. The similar molecular mechanisms and the common genetic signature shared by COPD and aging suggest that immunosenescence may contribute to the development of COPD.

Beliefs about personal control and self-management in 30-40 year olds living with Inflammatory Bowel Disease: a qualitative study.

PubMed

Cooper, Joanne M; Collier, Jacqueline; James, Veronica; Hawkey, Christopher J

2010-12-01

Inflammatory Bowel Disease is a collective term for two distinct long term conditions: Ulcerative Colitis and Crohn's disease. There is increasing emphasis on patients taking greater personal control and self-management of this condition, reflecting earlier research into the management of chronic illness. Nurses play a pivotal role in this process, yet how optimal personal control is self-assessed and self-managed in Inflammatory Bowel Disease is poorly understood. This study set out to explore beliefs about personal control and self-management of Inflammatory Bowel Disease. It focused on the role of physical, psychological and socio-economic factors within the individual's life experience. A qualitative approach was used comprising 24, one-to-one, semi-structured interviews with participants aged 30-40 years. Participants with a histological diagnosis of Inflammatory Bowel Disease for at least 12 months were eligible and recruited by gastrointestinal specialist staff from outpatient clinics at a large National Health Service Trust in the United Kingdom. Interviews were transcribed verbatim. Data analysis was informed by existing theories of personal control and used the 'systematic framework analysis' approach. In addition to existing theories of personal control, self-discrepancy theory helped to explain how people viewed the control and self-management of Inflammatory Bowel Disease. One main theme emerged from the findings: 'Reconciliation of the self in IBD', this was supported by three sub-themes and eight basic themes. Some participants found that being unable to control and predict the course of their condition was distressing, however for others this limited control was not viewed as a negative outcome. Being able to share control of IBD with specialist health care staff was beneficial, and participants stated that other priorities in life were as equally important to manage and control. A key barrier to ensuring greater personal control and self-management was a lack of knowledge and awareness by non-specialist health care staff, employers and the wider society. Nurses involved in the care of individuals with Inflammatory Bowel Disease should support and prepare patients for the discrepancies and uncertainties of living with the condition. Greater training about Inflammatory Bowel Disease is recommended, specifically for non-specialist health care staff and employers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.

PubMed

Villa, Valentina; Thellung, Stefano; Corsaro, Alessandro; Novelli, Federica; Tasso, Bruno; Colucci-D'Amato, Luca; Gatta, Elena; Tonelli, Michele; Florio, Tullio

2016-01-01

Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9 microglial cells in vitro. This effect was characterized by cell proliferation arrest and induction of a secretory phenotype, releasing prostaglandin E2 (PGE2) and nitric oxide (NO). Conditioned medium from PrP90-231-treated microglia induced in vitro cytotoxicity of A1 mesencephalic neurons, supporting the notion that soluble mediators released by activated microglia contributes to the neurodegeneration during prion diseases. The neuroinflammatory role of COX activity, and its potential targeting for anti-prion therapies, was tested measuring the effects of ketoprofen and celecoxib (preferential inhibitors of COX1 and COX2, respectively) on PrP90-231-induced microglial activation. Celecoxib, but not ketoprofen significantly reverted the growth arrest as well as NO and PGE2 secretion induced by PrP90-231, indicating that PrP90-231 pro-inflammatory response in microglia is mainly dependent on COX2 activation. Taken together, these data outline the importance of microglia in the neurotoxicity occurring during prion diseases and highlight the potentiality of COX2-selective inhibitors to revert microglia as adjunctive pharmacological approach to contrast the neuroinflammation-dependent neurotoxicity.

Etiopathogenesis, clinical diagnosis and treatment of thromboangiitis obliterans – current practices

PubMed Central

Joviliano, Edwaldo Edner; Dellalibera-Joviliano, Renata; Dalio, Marcelo; Évora, Paulo RB; Piccinato, Carlos E

2009-01-01

Thromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder that affects small- and medium-sized arteries, and arm and leg veins of young smokers. Several different diagnostic criteria have been offered for the diagnosis of TAO. Clinically, it manifests as migratory thrombophlebitis or signs of arterial insufficiency in the extremities. It is characterized by highly cellular and inflammatory occlusive thrombi, primarily of the distal extremities. Thromboses are often occlusive and sometimes display moderate, nonspecific inflammatory infiltrate, consisting mostly of polymorphonuclear leukocytes, mononuclear cells and rare multinuclear giant cells. The immune system appears to play a critical role in the etiology of TAO. However, knowledge about immunological aspects involved in the progression of vascular tissue inflammation, and consequently, the evolution of this disease, is still limited. There are several studies that suggest the involvement of genetic factors and results have shown increasing levels of antiendothelial cell antibodies in patients with active disease. Vasodilation is impaired in patients with TAO. TAO disorder may actually be an autoimmune disorder, probably initiated by an unknown antigen in the vascular endothelium, possibly a component of nicotine. There are various therapies available for treatment of TAO, but the major and indispensable measure is smoking cessation. Except for discontinuation of tobacco use, no forms of therapy are definitive. Sympathectomy, cilostazol and prostaglandin analogues (prostacyclin or prostaglandin E) have been used in specific conditions. Recently, therapeutic angiogenesis with autologous transplantation of bone marrow mononuclear cells has been studied in patients with critical limb ischemia. PMID:22477511

Nanoemulsion-based gel formulations of COX-2 inhibitors for enhanced efficacy in inflammatory conditions

NASA Astrophysics Data System (ADS)

Lala, R. R.; Awari, N. G.

2014-02-01

In the present study, we have investigated the potential of a nanoemulsion (thermodynamically stable transparent dispersions of oil and water having a droplet size <200 nm) formulation for the topical delivery of COX-2 inhibitors using etoricoxib as a model drug. Various oil-in-water nanoemulsions were prepared by the spontaneous emulsification method. The nanoemulsion area was identified by constructing pseudo-ternary phase diagrams. The prepared nanoemulsions were subjected to thermodynamic stability testing. Those that passed these tests were characterized for viscosity, droplet size and differential scanning calorimetry. Topical permeation of etoricoxib through porcine abdominal skin was estimated using the Franz diffusion cell. The ex vivo skin permeation profile of optimized formulations was compared with that of etoricoxib conventional gel. A significant increase in permeability was observed in optimized nanoemulsion formulations consisting of 2 % w/w of etoricoxib, 20 % w/w of Triacetin, 38 % w/w of a surfactant mixture (Cremophor RH 40:Transcutol P), and 42 % w/w of water. The anti-inflammatory effects of this formulation on carrageenan-induced paw edema in rats showed a significant increase in the percent inhibition value (84.61 % with the nanoemulsion gel and 92.30 % with the nanoemulsion) as compared with the conventional gel (69.23 %) after 6 h when compared with etoricoxib conventional gel. These results suggest that nanoemulsions can serve as potential vehicles for improved transdermal delivery of anti-inflammatory agents such as etoricoxib.

[Cytokine dysregulation in children with chronic catarrhal gingivitis living in polluted areas with fluoride and iodine deficiency].

PubMed

Bezvushko, E V; Malko, N V

The aim of the research was to study the state of oral liquid immunity in children with chronic catarrhal gingivitis living in unfavorable environmental conditions. The study included 190 children with chronic catarrhal gingivitis (CCG): 110 children aged 7, 12 and 15 years and residing in ecologically unfavorable areas of Lviv region and 80 children living in 'conditionally clean' region which constituted comparison group. Children with CCG from polluted areas had increased content of pro-inflammatory cytokines and reduction of anti-inflammatory cytokines compared to controls. The level of pro-inflammatory cytokines was age-depended in both groups but in children from ecologically unfavorable region this tendency was more pronounced. Thus, changes of indicators of interleukin spectrum in children with CCG depend not only on age and degree of severity of periodontium pathology but also on ecological living conditions.

Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

PubMed Central

Jope, Richard S.; Yuskaitis, Christopher J.; Beurel, Eléonore

2007-01-01

Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer’s disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions. PMID:16944320

Umbilical Cord Blood Transplantation Corrects Very Early-Onset Inflammatory Bowel Disease in Chinese Patients With IL10RA-Associated Immune Deficiency.

PubMed

Peng, Kaiyue; Qian, Xiaowen; Huang, Zhiheng; Lu, Junping; Wang, Yuhuan; Zhou, Ying; Wang, Huijun; Wu, Bingbing; Wang, Ying; Chen, Lingli; Zhai, Xiaowen; Huang, Ying

2018-05-18

Hematopoietic stem cell transplantation is considered the only curative therapy for very early-onset inflammatory bowel disease with specific immune defects, such as interleukin-10 receptor deficiency. We performed reduced-intensity conditioning before umbilical cord blood transplantation in patients with interleukin-10 receptor-A deficiency. We enrolled 9 very early-onset inflammatory bowel disease patients with typical manifestations. We diagnosed the patients with interleukin-10 receptor-A deficiency by whole-exome sequencing. Umbilical cord blood transplantation was performed in all 9 patients. Eight patients received the reduced-intensity conditioning regimen, and 1 patient received the myeloablative conditioning regimen. All 9 patients received transplantation between the ages of 6 months to 43 months (average, 16.8 months) with body weights ranging from 3 to 10.4 kg (average, 6.6 kg). The patients displayed complete chimerism at 2-8 weeks after transplantation; 6 patients achieved complete remission without evidence of graft-vs-host disease or infections; 1 patient died of chronic lung graft-vs-host disease at 6 months post-transplantation; and the other 2 patients died of sepsis post-transplantation because of unsuccessful engraftments. Severe malnutrition and growth retardation associated with interleukin-10 receptor-A deficiency were significantly improved post-transplantation. We recommend umbilical cord blood transplantation as a potential treatment for very early-onset inflammatory bowel disease with a defined monogenic immunodeficiency, and we suggest that reduced-intensity conditioning chemotherapy is more suitable than myeloablative conditioning for patients with severe malnutrition and bowel disease. We have demonstrated success with reduced-intensity conditioning for interleukin-10 receptor-A deficiency in pediatric patients with severe clinical conditions. 10.1093/ibd/izy028_video1izy028.video15786489183001.

Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis

PubMed Central

Kjelgaard-Petersen, Cecilie; Siebuhr, Anne Sofie; Christiansen, Thorbjørn; Ladel, Christoph; Karsdal, Morten; Bay-Jensen, Anne-Christine

2015-01-01

Abstract Objective: Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium. Methods: Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in the conditioned medium. Results: TNFα significantly increased C1M up to seven-fold (p = 0.0002), C3M up to 24-fold (p = 0.0011), and acMMP3 up to 14-fold (p < 0.0001) in SMEs. IL-1β also significantly increased C1M up to five-fold (p = 0.00094), C3M four-fold (p = 0.007), and acMMP3 18-fold (p < 0.0001) in SMEs. Conclusion: The biomarkers C1M, C3M, and acMMP-3 were synovitis biomarkers ex vivo and provide a translational tool together with the SME model. PMID:26863055

Characterization of kidney CD45intCD11bintF4/80+MHCII+CX3CR1+Ly6C- "intermediate mononuclear phagocytic cells".

PubMed

Lee, Sul A; Noel, Sanjeev; Sadasivam, Mohanraj; Allaf, Mohamad E; Pierorazio, Phillip M; Hamad, Abdel R A; Rabb, Hamid

2018-01-01

Kidney immune cells play important roles in pathogenesis of many diseases, including ischemia-reperfusion injury (IRI) and transplant rejection. While studying murine kidney T cells, we serendipitously identified a kidney mononuclear phagocytic cell (MPC) subset characterized by intermediate surface expression of CD45 and CD11b. These CD45intCD11bint MPCs were further identified as F4/80+MHCII+CX3CR1+Ly6C- cells, comprising ~17% of total CD45+ cells in normal mouse kidney (P < 0.01) and virtually absent from all other organs examined except the heart. Systemic clodronate treatment had more significant depletive effect on the CD45intCD11bint population (77.3%±5.9%, P = 0.03) than on CD45highCD11b+ population (14.8%±16.6%, P = 0.49). In addition, CD45intCD11bint MPCs had higher phagocytic function in the normal kidney (35.6%±3.3% vs. 24.1%±2.2%, P = 0.04), but lower phagocytic capacity in post-ischemic kidney (54.9%±1.0% vs. 67.8%±1.9%, P < 0.01) compared to the CD45highCD11b+ population. Moreover, the CD45intCD11bint population had higher intracellular production of the pro-inflammatory tumor necrosis factor (TNF)-α (58.4%±5.2% vs. 27.3%±0.9%, P < 0.001) after lipopolysaccharide (LPS) stimulation and lower production of the anti-inflammatory interleukin (IL)-10 (7.2%±1.3% vs. 14.9%±2.2%, P = 0.02) following kidney IRI, suggesting a functional role under inflammatory conditions. The CD45intCD11bint cells increased early after IRI, and then abruptly decreased 48h later, whereas CD45highCD11b+ cells steadily increased after IRI before declining at 72h (P = 0.03). We also identified the CD45intCD11bint MPC subtype in human kidney. We conclude that CD45intCD11bint F4/80+MHCII+CX3CR1+Ly6C-population represent a unique subset of MPCs found in both mouse and human kidneys. Future studies will further characterize their role in kidney health and disease.

Conditioned medium from persistently RSV-infected macrophages alters transcriptional profile and inflammatory response of non-infected macrophages.

PubMed

Rivera-Toledo, Evelyn; Salido-Guadarrama, Iván; Rodríguez-Dorantes, Mauricio; Torres-González, Laura; Santiago-Olivares, Carlos; Gómez, Beatriz

2017-02-15

Cells susceptible to persistent viral infections undergo important changes in their biological functions as a consequence of the expression of viral gene products that are capable of altering the gene expression profile of the host cell. Previously, we reported that persistence of the RSV genome in a mouse macrophage cell line induces important alterations in cell homeostasis, including constitutive expression of IFN-β and other pro-inflammatory cytokines. Here, we postulated that changes in the homeostasis of non-infected macrophages could be induced by soluble factors secreted by persistently RSV- infected macrophages. To test this hypothesis, non-infected mouse macrophages were treated with conditioned medium (CM) collected from cultures of persistently RSV-infected macrophages. Total RNA was extracted and a microarray-based gene expression analysis was performed. Non-infected macrophages, treated under similar conditions with CM obtained from cultures of non-infected macrophages, were used as a control to establish differential gene expression between the two conditions. Results showed that CM from the persistently RSV-infected cultures altered expression of a total of 95 genes in non-infected macrophages, resulting in an antiviral gene-transcription profile along with inhibition of the inflammatory response, since some inflammatory genes were down-regulated, including Nlrp3 and Il-1 β, both related to the inflammasome pathway. However, down-regulation of Nlrp3 and Il-1 β was reversible upon acute RSV infection. Additionally, we observed that the inflammatory response, evaluated by secreted IL-1 β, a final product of the inflammasome activity, was enhanced during acute RSV infection in macrophages treated with CM from persistently RSV-infected cultures, compared to that in macrophages treated with the control CM. This suggests that soluble factors secreted during RSV persistence may induce an exacerbated inflammatory response in non-infected cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.

PubMed

Woo, Hae-Mi; Kang, Ji-Hye; Kawada, Teruo; Yoo, Hoon; Sung, Mi-Kyung; Yu, Rina

2007-02-13

Inflammation plays a key role in obesity-related pathologies such as cardiovascular disease, type II diabetes, and several types of cancer. Obesity-induced inflammation entails the enhancement of the recruitment of macrophages into adipose tissue and the release of various proinflammatory proteins from fat tissue. Therefore, the modulation of inflammatory responses in obesity may be useful for preventing or ameliorating obesity-related pathologies. Some spice-derived components, which are naturally occurring phytochemicals, elicit antiobesity and antiinflammatory properties. In this study, we investigated whether active spice-derived components can be applied to the suppression of obesity-induced inflammatory responses. Mesenteric adipose tissue was isolated from obese mice fed a high-fat diet and cultured to prepare an adipose tissue-conditioned medium. Raw 264.7 macrophages were treated with the adipose tissue-conditioned medium with or without active spice-derived components (i.e., diallyl disulfide, allyl isothiocyanate, piperine, zingerone and curcumin). Chemotaxis assay was performed to measure the degree of macrophage migration. Macrophage activation was estimated by measuring tumor necrosis factor-alpha (TNF-alpha), nitric oxide, and monocyte chemoattractant protein-1 (MCP-1) concentrations. The active spice-derived components markedly suppressed the migration of macrophages induced by the mesenteric adipose tissue-conditioned medium in a dose-dependent manner. Among the active spice-derived components studied, allyl isothiocyanate, zingerone, and curcumin significantly inhibited the cellular production of proinflammatory mediators such as TNF-alpha and nitric oxide, and significantly inhibited the release of MCP-1 from 3T3-L1 adipocytes. Our findings suggest that the spice-derived components can suppress obesity-induced inflammatory responses by suppressing adipose tissue macrophage accumulation or activation and inhibiting MCP-1 release from adipocytes. These spice-derived components may have a potential to improve chronic inflammatory conditions in obesity.

Inflammatory hyperplasia: From diagnosis to treatment

PubMed Central

Shukla, Pradeep; Dahiya, Varun; Kataria, Prerna; Sabharwal, Shreya

2014-01-01

Gingival enlargement, the currently accepted terminology for an increase in the size of the gingiva, is a common feature of gingival disease. Local and systemic factors influence the gingival conditions of the patient. These factors results in a spectrum of diseases that can be developmental, reactive and inflammatory to neoplastic. In this article, the history, etiology, clinical and histopathological features, treatment strategies and preventive protocol of inflammatory hyperplasia are discussed. PMID:24744554

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis.

PubMed

Soendergaard, Christoffer; Kvist, Peter Helding; Thygesen, Peter; Reslow, Mats; Nielsen, Ole Haagen; Kopchick, John Joseph; Holm, Thomas Lindebo

2017-09-23

Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH-insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular mechanisms governing GH resistance was verified. Also, the therapeutic potential of GH on mucosal healing was tested in the PAC model. Inflammation induced intestinal GH resistance in UC and experimental colitis by down-regulating GHR expression and up-regulating suppressor of cytokine signalling (SOCS) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation or mucosal healing. The high transcriptional similarity between UC and experimental colitis accentuates the formation of intestinal GH resistance during inflammation. Inflammation-induced GH resistance not only impairs general growth but induces a state of local resistance, which potentially impairs the actions of GH on mucosal healing during colitis when using long-acting GH therapy.

Characterization of Growth Hormone Resistance in Experimental and Ulcerative Colitis

PubMed Central

Kvist, Peter Helding; Thygesen, Peter; Reslow, Mats; Nielsen, Ole Haagen; Kopchick, John Joseph; Holm, Thomas Lindebo

2017-01-01

Growth hormone (GH) resistance may develop as a consequence of inflammation during conditions such as inflammatory bowel disease, encompassing ulcerative colitis (UC). However, the specific role of the GH–insulin growth factor (IGF)-1-axis and/or the functional consequences of GH resistance in this condition are unclear. In situ hybridization targeting the GH receptor (GHR) and relevant transcriptional analyses were performed in patients with UC and in IL-10 knock-out mice with piroxicam accelerated colitis (PAC). Using cultured primary epithelial cells, the effects of inflammation on the molecular mechanisms governing GH resistance was verified. Also, the therapeutic potential of GH on mucosal healing was tested in the PAC model. Inflammation induced intestinal GH resistance in UC and experimental colitis by down-regulating GHR expression and up-regulating suppressor of cytokine signalling (SOCS) proteins. These effects are driven by pro-inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6) as confirmed using primary epithelial cells. Treatment of experimental colitis with GH increased IGF-1 and body weight of the mice, but had no effects on colonic inflammation or mucosal healing. The high transcriptional similarity between UC and experimental colitis accentuates the formation of intestinal GH resistance during inflammation. Inflammation-induced GH resistance not only impairs general growth but induces a state of local resistance, which potentially impairs the actions of GH on mucosal healing during colitis when using long-acting GH therapy. PMID:28946616

Cutaneous manifestations associated with adult-onset Still's disease: important diagnostic values.

PubMed

Yamamoto, Toshiyuki

2012-08-01

Adult-onset Still's disease (AOSD) is a systemic inflammatory condition, characterized by a high spiking fever, leukocytosis with neutrophilia, arthralgia, and skin rash. Typical skin rash is an evanescent, salmon-pink erythema predominantly involving extremities, which is included as one of the diagnostic criteria; however, recent findings show that not only typical evanescent rash but also various skin lesions are associated with AOSD. The representative characteristic skin lesion among the non-classical skin rash is called persistent pruritic papules and plaques, which presents erythematous, slightly scaly papules with linear configuration on the trunk. Interestingly, persistent pruritic papules and plaques show unique histological features such as peculiar, distinctive distribution of dyskeratotic keratinocytes in the cornified layers as well as in the epidermis. Other non-classical skin lesions include urticaria. Current insights suggest that several inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-18, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) play a pathogenic role in AOSD. In particular, IL-18 is suggested to play a crucial role in activating macrophages, favoring Th1 type cytokine production. IL-18 induces IFN-γ, IL-17, and TNF-α, which may play an important pathogenic role in AOSD. It is important to recognize the common and/or uncommon skin conditions of AOSD for early correct diagnosis. In this review, various skin lesions are introduced, and the complication with histiocytic necrotizing lymphadenitis (Kikuchi disease) is further discussed.

An In Vitro Model of the Blood-Brain Barrier: Naegleria fowleri Affects the Tight Junction Proteins and Activates the Microvascular Endothelial Cells.

PubMed

Coronado-Velázquez, Daniel; Betanzos, Abigail; Serrano-Luna, Jesús; Shibayama, Mineko

2018-04-14

Naegleria fowleri causes a fatal disease known as primary amoebic meningoencephalitis. This condition is characterized by an acute inflammation that originates from the free passage of peripheral blood cells to the central nervous system through the alteration of the blood-brain barrier. In this work, we established models of the infection in rats and in a primary culture of endothelial cells from rat brains with the aim of evaluating the activation and the alterations of these cells by N. fowleri. We proved that the rat develops the infection similar to the mouse model. We also found that amoebic cysteine proteases produced by the trophozoites and the conditioned medium induced cytopathic effect in the endothelial cells. In addition, N. fowleri can decrease the transendothelial electrical resistance by triggering the destabilization of the tight junction proteins claudin-5, occludin, and ZO-1 in a time-dependent manner. Furthermore, N. fowleri induced the expression of VCAM-1 and ICAM-1 and the production of IL-8, IL-1β, TNF-α, and IL-6 as well as nitric oxide. We conclude that N. fowleri damaged the blood-brain barrier model by disrupting the intercellular junctions and induced the presence of inflammatory mediators by allowing the access of inflammatory cells to the olfactory bulbs. © 2018 The Author(s) Journal of Eukaryotic Microbiology © 2018 International Society of Protistologists.

Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines.

PubMed

Horsch, Marion; Aguilar-Pimentel, Juan Antonio; Bönisch, Clemens; Côme, Christophe; Kolster-Fog, Cathrine; Jensen, Klaus T; Lund, Anders H; Lee, Icksoo; Grossman, Lawrence I; Sinkler, Christopher; Hüttemann, Maik; Bohn, Erwin; Fuchs, Helmut; Ollert, Markus; Gailus-Durner, Valérie; de Angelis, Martin Hrabĕ; Beckers, Johannes

2015-01-01

We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype-envirotype interactions for other diseases.

Cox4i2, Ifit2, and Prdm11 Mutant Mice: Effective Selection of Genes Predisposing to an Altered Airway Inflammatory Response from a Large Compendium of Mutant Mouse Lines

PubMed Central

Bönisch, Clemens; Côme, Christophe; Kolster-Fog, Cathrine; Jensen, Klaus T.; Lund, Anders H.; Lee, Icksoo; Grossman, Lawrence I.; Sinkler, Christopher; Hüttemann, Maik; Bohn, Erwin; Fuchs, Helmut; Ollert, Markus; Gailus-Durner, Valérie; Hrabĕ de Angelis, Martin; Beckers, Johannes

2015-01-01

We established a selection strategy to identify new models for an altered airway inflammatory response from a large compendium of mutant mouse lines that were systemically phenotyped in the German Mouse Clinic (GMC). As selection criteria we included published gene functional data, as well as immunological and transcriptome data from GMC phenotyping screens under standard conditions. Applying these criteria we identified a few from several hundred mutant mouse lines and further characterized the Cox4i2tm1Hutt, Ifit2tm1.1Ebsb, and Prdm11tm1.1ahl lines following ovalbumin (OVA) sensitization and repeated OVA airway challenge. Challenged Prdm11tm1.1ahl mice exhibited changes in B cell counts, CD4+ T cell counts, and in the number of neutrophils in bronchoalveolar lavages, whereas challenged Ifit2tm1.1Ebsb mice displayed alterations in plasma IgE, IgG1, IgG3, and IgM levels compared to the challenged wild type littermates. In contrast, challenged Cox4i2tm1Hutt mutant mice did not show alterations in the humoral or cellular immune response compared to challenged wild type mice. Transcriptome analyses from lungs of the challenged mutant mouse lines showed extensive changes in gene expression in Prdm11tm1.1ahl mice. Functional annotations of regulated genes of all three mutant mouse lines were primarily related to inflammation and airway smooth muscle (ASM) remodeling. We were thus able to define an effective selection strategy to identify new candidate genes for the predisposition to an altered airway inflammatory response under OVA challenge conditions. Similar selection strategies may be used for the analysis of additional genotype – envirotype interactions for other diseases. PMID:26263558

COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice

PubMed Central

Vardeh, Daniel; Wang, Dairong; Costigan, Michael; Lazarus, Michael; Saper, Clifford B.; Woolf, Clifford J.; FitzGerald, Garret A.; Samad, Tarek A.

2009-01-01

A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation–induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this. PMID:19127021

Solid-phase microextraction based on an agarose-chitosan-multiwalled carbon nanotube composite film combined with HPLC-UV for the determination of non-steroidal anti-inflammatory drugs in aqueous samples.

PubMed

Wan Ibrahim, Wan Nazihah; Sanagi, Mohd Marsin; Mohamad Hanapi, Nor Suhaila; Kamaruzaman, Sazlinda; Yahaya, Noorfatimah; Wan Ibrahim, Wan Aini

2018-06-07

We describe the preparation, characterization and application of a composite film adsorbent based on blended agarose-chitosan-multi-walled carbon nanotubes for the preconcentration of selected non-steroidal anti-inflammatory drugs in aqueous samples before determination by high-performance liquid chromatography with UV detection. The composite film showed high surface area (4.0258 m 2 /g) and strong hydrogen bonding between multi-walled carbon nanotubes and agarose/chitosan matrix, which prevent adsorbent deactivation and ensure long-term stability. Several parameters, namely, sample pH, addition of salt, extraction time, desorption solvent and concentration of multi-walled carbon nanotubes in the composite film were optimized using a one-factor-at-time approach. The optimum extraction conditions obtained were as follows: isopropanol as conditioning solvent, 10 mL of sample solution at pH 2, extraction time of 30 min, stirring speed of 600 rpm, 100 μL of isopropanol as desorption solvent, desorption time of 5 min under ultrasonication, and 0.4% w/v of composite film. Under optimized conditions, the calibration curved showed good linearity in the range of 1-500 ng/mL (r 2  = 0.997-0.999), good limits of detection (0.89-8.05 ng/mL) were obtained with good relative standard deviations of < 4.59% (n = 3) for the determination of naproxen, diclofenac sodium salt and mefenamic acid drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease

PubMed Central

Zhang, Liping; Rajan, Vik; Lin, Eugene; Hu, Zhaoyong; Han, H. Q.; Zhou, Xiaolan; Song, Yanping; Min, Hosung; Wang, Xiaonan; Du, Jie; Mitch, William E.

2011-01-01

Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC50 ∼1.2 nM) reversed the loss of body weight (≈5–7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38±1.29%; P<0.05), increased protein synthesis in extensor digitorum longus muscles (13.21±1.09%; P<0.05), markedly enhanced satellite cell function, and improved IGF-1 intracellular signaling. In cultured muscle cells, TNF-α increased myostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.—Zhang, L., Rajan, V., Lin, E., Hu, Z., Han, H.Q., Zhou, X., Song, Y., Min, H., Wang, X., Du, J., Mitch, W. E. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. PMID:21282204

Chronic inflammatory disease and osteopathy: a systematic review.

PubMed

Cicchitti, Luca; Martelli, Marta; Cerritelli, Francesco

2015-01-01

Chronic inflammatory diseases (CID) are globally highly prevalent and characterized by severe pathological medical conditions. Several trials were conducted aiming at measuring the effects of manipulative therapies on patients affected by CID. The purpose of this review was to explore the extent to which osteopathic manipulative treatment (OMT) can be benefi-cial in medical conditions also classified as CID. This review included any type of experimental study which enrolled sub-jects with CID comparing OMT with any type of control procedure. The search was conducted on eight databases in January 2014 using a pragmatic literature search approach. Two independent re-viewers conducted study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Heterogeneity was assessed and meta-analysis performed where possible. 10 studies met the inclusion criteria for this review enrolling 386 subjects. The search identified six RCTs, one laboratory study, one cross-over pilot studies, one observation-al study and one case control pilot study. Results suggest a potential effect of osteopathic medicine on patients with medical pathologies associated with CID (in particular Chronic Obstructive Pul-monary Disease (COPD), Irritable Bowel Syndrome, Asthma and Peripheral Arterial Disease) com-pared to no treatment or sham therapy although data remain elusive. Moreover one study showed possible effects on arthritis rat model. Meta-analysis was performed for COPD studies only show-ing no effect of any type of OMT applied versus control. No major side effects were reported by those receiving OMT. The present systematic review showed inconsistent data on the effect of OMT in the treatment of medical conditions potentially associated with CID, however the OMT appears to be a safe approach. Further more robust trials are needed to determine the direction and magnitude of the effect of OMT and to generalize favorable results.

Differential impact of glucose levels and advanced glycation end-products on tubular cell viability and pro-inflammatory/profibrotic functions.

PubMed

Franko, Benoit; Brault, Julie; Jouve, Thomas; Beaumel, Sylvain; Benhamou, Pierre-Yves; Zaoui, Philippe; Stasia, Marie José

2014-09-05

High glucose (HG) or synthetic advanced glycation end-products (AGE) conditions are generally used to mimic diabetes in cellular models. Both models have shown an increase of apoptosis, oxidative stress and pro-inflammatory cytokine production in tubular cells. However, the impact of the two conditions combined has rarely been studied. In addition, the impact of glucose level variation due to cellular consumption is not clearly characterized in such experiments. Therefore, the aim of this study was to compare the effect of HG and AGE separately and of both on tubular cell phenotype changes in the HK2 cell line. Moreover, glucose consumption was monitored every hour to maintain the glucose level by supplementation throughout the experiments. We thus observed a significant decrease of apoptosis and H2O2 production in the HK2 cell. HG or AGE treatment induced an increase of total and mitochondrial apoptosis as well as TGF-β release compared to control conditions; however, AGE or HG led to apoptosis preferentially involving the mitochondria pathway. No cumulative effect of HG and AGE treatment was observed on apoptosis. However, a pretreatment with RAGE antibodies partially abolished the apoptotic effect of HG and completely abolished the apoptotic effect of AGE. In conclusion, tubular cells are sensitive to the lack of glucose as well as to the HG and AGE treatments, the AGE effect being more deleterious than the HG effect. Absence of a potential synergistic effect of HG and AGE could indicate that they act through a common pathway, possibly via the activation of the RAGE receptors. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of novel Cyclooxygenase-2-dependent genes in Helicobacter pylori infection in vivo

PubMed Central

Walduck, Anna K; Weber, Matthias; Wunder, Christian; Juettner, Stefan; Stolte, Manfred; Vieth, Michael; Wiedenmann, Bertram; Meyer, Thomas F; Naumann, Michael; Hoecker, Michael

2009-01-01

Background Helicobacter pylori is a crucial determining factor in the pathogenesis of benign and neoplastic gastric diseases. Cyclooxygenase-2 (Cox-2) is the inducible key enzyme of arachidonic acid metabolism and is a central mediator in inflammation and cancer. Expression of the Cox-2 gene is up-regulated in the gastric mucosa during H. pylori infection but the pathobiological consequences of this enhanced Cox-2 expression are not yet characterized. The aim of this study was to identify novel genes down-stream of Cox-2 in an in vivo model, thereby identifying potential targets for the study of the role of Cox- 2 in H. pylori pathogenesis and the initiation of pre- cancerous changes. Results Gene expression profiles in the gastric mucosa of mice treated with a specific Cox-2 inhibitor (NS398) or vehicle were analysed at different time points (6, 13 and 19 wk) after H. pylori infection. H. pylori infection affected the expression of 385 genes over the experimental period, including regulators of gastric physiology, proliferation, apoptosis and mucosal defence. Under conditions of Cox-2 inhibition, 160 target genes were regulated as a result of H. pylori infection. The Cox-2 dependent subset included those influencing gastric physiology (Gastrin, Galr1), epithelial barrier function (Tjp1, connexin45, Aqp5), inflammation (Icam1), apoptosis (Clu) and proliferation (Gdf3, Igf2). Treatment with NS398 alone caused differential expression of 140 genes, 97 of which were unique, indicating that these genes are regulated under conditions of basal Cox-2 expression. Conclusion This study has identified a panel of novel Cox-2 dependent genes influenced under both normal and the inflammatory conditions induced by H. pylori infection. These data provide important new links between Cox-2 and inflammatory processes, epithelial repair and integrity. PMID:19317916

Analgesic, Anti- inflammatory, Anti- lipoxygenase Activity and Characterization of Three Bioactive Compounds in the Most Active Fraction of Leptadenia reticulata (Retz.)Wight & Arn. – A Valuable Medicinal Plant

PubMed Central

Mohanty, Sudipta Kumar; Swamy, Mallappa Kumara; Middha, Sushil Kumar; Prakash, Lokesh; Subbanarashiman, Balasubramanya; Maniyam, Anuradha

2015-01-01

Leptadenia reticulata was reported to be used for several medicinal purposes. The present study was undertaken to evaluate anti-inflammatory, analgesic and lipid peroxidation inhibition activities of L. reticulata. The anti-inflammatory assay was performed by λ-carrageenan and formalin induced paw edema test. Pro inflammatory mediators (IL2, IL6, TNF-α) in serum of treated and control organism were analyzed by quantitative ELISA. Lipid peroxidation inhibition was measured by thiobarbituric acid reactive substances (TBARS) assay. Analysis of the most active fraction revealed the presence of one phenolic compound (p-coumaric acid), two flavonoids (rutin and quercetin) which also determined quantitatively. The ethyl acetate fraction at 600 mg/Kg significantly inhibited λ-carrageenan and formalin induced paw edema by 60.59% and 59.24% respectively. Notable reduction in percentage of writhing (76.25%), induced by acetic acid signifies the potent analgesic activity. Lower level of pro-inflammatory cytokines (IL-2, IL-6, TNF-α) in serum at the 4th hour of λ-Carrageenan injection indicated the inhibition of cyclooxigenase-2 (Cox-2), Nitric oxide (NO) and release of prostaglandin to prevent inflammation. The study also demonstrated the decrease in malonaldehyde (MDA) concentration which revealed the lipid peroxidation inhibition potential of the plant. Our finding provides evidence for potent biological activities in tested model which is supported by its characterized bioactive compounds and ethnomedicinal relevance. PMID:26330883

Impact of Anesthetics on Immune Functions in a Rat Model of Vagus Nerve Stimulation

PubMed Central

Picq, Chloé A.; Clarençon, Didier; Sinniger, Valérie E.; Bonaz, Bruno L.; Mayol, Jean-François S.

2013-01-01

Vagus nerve stimulation (VNS) has been successfully performed in animals for the treatment of different experimental models of inflammation. The anti-inflammatory effect of VNS involves the release of acetylcholine by vagus nerve efferent fibers inhibiting pro-inflammatory cytokines (e.g. TNF-α) produced by macrophages. Moreover, it has recently been demonstrated that splenic lymphocytic populations may also be involved. As anesthetics can modulate the inflammatory response, the current study evaluated the effect of two different anesthetics, isoflurane and pentobarbital, on splenic cellular and molecular parameters in a VNS rat model. Spleens were collected for the characterization of lymphocytes sub-populations by flow cytometry and quantification of cytokines secretion after in vitro activation. Different results were observed depending on the anesthetic used. The use of isoflurane displayed a non-specific effect of VNS characterized by a decrease of most splenic lymphocytes sub-populations studied, and also led to a significantly lower TNF-α secretion by splenocytes. However, the use of pentobarbital brought to light immune modifications in non-stimulated animals that were not observed with isoflurane, and also revealed a specific effect of VNS, notably at the level of T lymphocytes’ activation. These differences between the two anesthetics could be related to the anti-inflammatory properties of isoflurane. In conclusion, pentobarbital is more adapted than isoflurane in the study of the anti-inflammatory effect of VNS on an anesthetized rat model in that it allows more accurate monitoring of subtle immunomodulatory processes. PMID:23840592

Anti-inflammatory and bronchodilatory constituents of leaf extracts of Anacardium occidentale L. in animal models.

PubMed

Awakan, Oluwakemi Josephine; Malomo, Sylvia Omonirume; Adejare, Abdullahi Adeyinka; Igunnu, Adedoyin; Atolani, Olubunmi; Adebayo, Abiodun Humphrey; Owoyele, Bamidele Victor

2018-01-01

Anacardium occidentale L. leaf is useful in the treatment of inflammation and asthma, but the bioactive constituents responsible for these activities have not been characterized. Therefore, this study was aimed at identifying the bioactive constituent(s) of A. occidentale ethanolic leaf extract (AOEL) and its solvent-soluble portions, and evaluating their effects on histamine-induced paw edema and bronchoconstriction. The bronchodilatory effect was determined by measuring the percentage protection provided by plant extracts in the histamine-induced bronchoconstriction model in guinea pigs. The anti-inflammatory effect of the extracts on histamine-induced paw edema in rats was determined by measuring the increase in paw diameter, after which the percent edema inhibition was calculated. The extracts were analyzed using gas chromatography-mass spectrometry to identify the bioactive constituents. Column chromatography and Fourier transform infrared spectroscopy were used respectively to isolate and characterize the constituents. The bronchodilatory and anti-inflammatory activities of the isolated bioactive constituent were evaluated. Histamine induced bronchoconstriction in the guinea pigs and edema in the rat paw. AOEL, hexane-soluble portion of AOEL, ethyl acetate-soluble portion of AOEL, and chloroform-soluble portion of AOEL significantly increased bronchodilatory and anti-inflammatory activities (P < 0.05). Oleamide (9-octadecenamide) was identified as the most abundant compound in the extracts and was isolated. Oleamide significantly increased bronchodilatory and anti-inflammatory activities by 32.97% and 98.41%, respectively (P < 0.05). These results indicate that oleamide is one of the bioactive constituents responsible for the bronchodilatory and anti-inflammatory activity of A. occidentale leaf, and can therefore be employed in the management of bronchoconstriction and inflammation. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

Anti-inflammatory and anti-bacterial activity, and cytotoxicity of halloysite surfaces.

PubMed

Cervini-Silva, Javiera; Nieto-Camacho, Antonio; Palacios, Eduardo; Montoya, José Ascención; Gómez-Vidales, Virginia; Ramírez-Apán, María Teresa

2013-11-01

Halloysite is a naturally-occurring nanomaterial occurring in the thousands of tons and that serves as biomaterial, with applications in the areas of biotechnology, pharmaceutical, and medical research. This study reports on the anti-inflammatory, cytotoxic, and anti-oxidant activity of halloysite Jarrahdale (collected at ∼ 45 km SE of Perth, Western Australia; JA), Dragon Mine (provided by Natural Nano Inc., Rochester, New York; NA), and Kalgoorie Archean (collected at Siberia, ∼ 85km NW of Kalgoorlie, West Australia; PA). Prior to biological testing, halloysites were characterized by 27Al and 29Si Nuclear Magnetic Resonance Spectroscopy, the anti-inflammatory activity was determined by (a) the mouse ear edema method, using 12-o-tetradecanoylphorbol-13-acetate (TPA) as anti-inflammatory agent; and (b) the myeloperoxidase enzymatic activity method (MPO). Cell viability was determined using the MTT method. Sample characterization by NMR method showed similar symmetry and atomic environments, with no evidence of distortion(s) due to shiftings in atomic ordering or electron density. The anti-inflammatory activity followed the order: PA>JA>NA, and remained invariant with time. Prolonged anti-inflammatory activity related inversely to surface area and lumen space. The low extent of infiltration at shorter reaction times confirmed a limiting number of active surface sites. EPR intensity signals followed the order: JA>NA>PA. The poor stabilization of RO species in PA suspensions was explained by tube alignment provoking occlusion, thus limiting transfer of H(+) or e(-) from-and-to the surface, and decreases in acidity associated to Al(oct). Cell viability (%) varied from one surface to the other, PA(92.3 ± 6.0), JA(84.9 ± 7.8), and NA(78.0 ± 5.6), but related directly to SBET values. Copyright © 2013 Elsevier B.V. All rights reserved.

The use of Brazilian propolis for discovery and development of novel anti-inflammatory drugs.

PubMed

Franchin, Marcelo; Freires, Irlan Almeida; Lazarini, Josy Goldoni; Nani, Bruno Dias; da Cunha, Marcos Guilherme; Colón, David Fernando; de Alencar, Severino Matias; Rosalen, Pedro Luiz

2018-06-10

Anti-Inflammatory drugs have been routinely used in the management of acute and chronic inflammatory conditions. Nevertheless, their undesirable side and adverse effects have encouraged the development of more selective, tolerable and efficacious drugs able to modulate the inflammatory process through distinct mechanisms than those of drugs currently available in the market, for instance, inhibition of leukocyte recruitment (chemotaxis, rolling, adhesion and transmigration). Natural products, including Brazilian propolis, have been considered a rich source of anti-inflammatory molecules due to a very complex phytochemical diversity. Brazil has at least thirteen distinct types of propolis and many bioactive compounds have been isolated therefrom, such as apigenin, artepillin C, vestitol, neovestitol, among others. These molecules were proven to play a significant immunomodulatory role through (i) inhibition of inflammatory cytokines (e.g. TNF-α) and chemokines (CXCL1/KC and CXCL2/MIP2); (ii) inhibition of IκBα, ERK1/2, JNK and p38MAPK phosphorylation; (iii) inhibition of NF-κB activation; and (iv) inhibition of neutrophil adhesion and transmigration (ICAM-1, VCAM-1 and E-selectin expression). In this review, we shed light on the new advances in the research of compounds isolated from Brazilian propolis from Apis mellifera bees as potentially novel anti-inflammatory drugs. The compilation of data and insights presented herein may open further avenues for the pharmacological management of oral and systemic inflammatory conditions. Further research should focus on clinical and acute/chronic toxicological validation of the most promising compounds described in this review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Clinical applications of bioactive milk components

PubMed Central

Newburg, David S.

2015-01-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications. PMID:26011900

Alexithymia and personality traits of patients with inflammatory bowel disease

PubMed Central

La Barbera, D.; Bonanno, B.; Rumeo, M. V.; Alabastro, V.; Frenda, M.; Massihnia, E.; Morgante, M. C.; Sideli, L.; Craxì, A.; Cappello, M.; Tumminello, M.; Miccichè, S.; Nastri, L.

2017-01-01

Psychological factors, specific lifestyles and environmental stressors may influence etiopathogenesis and evolution of chronic diseases. We investigate the association between Chronic Inflammatory Bowel Diseases (IBD) and psychological dimensions such as personality traits, defence mechanisms, and Alexithymia, i.e. deficits of emotional awareness with inability to give a name to emotional states. We analyzed a survey of 100 patients with IBD and a control group of 66 healthy individuals. The survey involved filling out clinical and anamnestic forms and administering five psychological tests. These were then analyzed by using a network representation of the system by considering it as a bipartite network in which elements of one set are the 166 individuals, while the elements of the other set are the outcome of the survey. We then run an unsupervised community detection algorithm providing a partition of the 166 participants into clusters. That allowed us to determine a statistically significant association between psychological factors and IBD. We find clusters of patients characterized by high neuroticism, alexithymia, impulsivity and severe physical conditions and being of female gender. We therefore hypothesize that in a population of alexithymic patients, females are inclined to develop psychosomatic diseases like IBD while males might eventually develop behavioral disorders. PMID:28150800

Clinical applications of bioactive milk components.

PubMed

Hill, David R; Newburg, David S

2015-07-01

Milk represents a unique resource for translational medicine: It contains a rich pool of biologically active molecules with demonstrated clinical benefits. The ongoing characterization of the mechanistic process through which milk components promote development and immunity has revealed numerous milk-derived compounds with potential applications as clinical therapies in infectious and inflammatory disease, cancer, and other conditions. Lactoferrin is an effective antimicrobial and antiviral agent in high-risk patient populations and a potentially potent adjuvant to chemotherapy in lung cancer. Enteric nutrition formulas supplemented with transforming growth factor β, a milk cytokine, have been shown to promote remission in pediatric Crohn's disease. A number of milk glycans, including human milk oligosaccharides, show promise in preclinical studies as antimicrobial and anti-inflammatory agents. While active preclinical investigations of human milk may soon result in large-scale production of human milk molecules, bovine milk components in many instances represent a practical source of bioactive milk compounds for use in clinical trials. This review summarizes current efforts to translate the compounds derived from human and bovine milk into effective clinical therapies. These efforts suggest a common pathway for the translation of milk-derived compounds into clinical applications.

Gastrointestinal Manifestations in X-linked Agammaglobulinemia

PubMed Central

Barmettler, Sara; Otani, Iris M.; Minhas, Jasmit; Abraham, Roshini S.; Chang, Yenhui; Dorsey, Morna J.; Ballas, Zuhair K.; Bonilla, Francisco A.; Ochs, Hans D.; Walter, Jolan E.

2017-01-01

Purpose X-linked agammaglobulinemia is a primary humoral immunodeficiency characterized by hypogammaglobulinemia and increased susceptibility to infection. Although there is increased awareness of autoimmune and inflammatory complications in XLA, the spectrum of gastrointestinal manifestations has not previously been fully explored. Methods We present a case report of a family with two affected patients with XLA. Given the gastrointestinal involvement of the grandfather in this family, we performed a retrospective descriptive analysis of XLA patients with reported diagnoses of GI manifestations and inflammatory bowel disease (IBD) or enteritis registered at the USIDNet, a national registry of primary immunodeficiencies. Results In this cohort of patients with XLA, we found that up to 35% had concurrent gastrointestinal manifestations, and 10% had reported diagnoses of IBD or enteritis. The most commonly reported mutations were missense, which have been associated with a less severe XLA phenotype in the literature. The severity of symptoms were wide-ranging, and management strategies were diverse and mainly experimental. Conclusions Patients with XLA may require close monitoring with particular attention for GI manifestations including IBD and infectious enteritis. Further studies are needed to improve diagnosis and management of GI conditions in XLA patients. PMID:28236219

Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

PubMed Central

Mishra, Gyan P.; Tamboli, Viral; Jwala, Jwala; Mitra, Ashim K.

2011-01-01

Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. PMID:21171952

Mesenchymal Stem Cell Therapy for Inflammatory Skin Diseases: Clinical Potential and Mode of Action.

PubMed

Shin, Tae-Hoon; Kim, Hyung-Sik; Choi, Soon Won; Kang, Kyung-Sun

2017-01-25

Inflammatory skin disorders that cause serious deterioration of the quality of life have become one of the major public concerns. Despite their significance, there is no fundamental cure to date. Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties which make them a promising tool for the treatment of various inflammatory diseases. Our recent preclinical and clinical studies have shown that MSCs can be successfully used for the treatment of atopic dermatitis (AD), one of the major inflammatory skin diseases. This observation along with similar reports from other groups revealed the efficacy and underlying mechanisms of MSCs in inflammatory dermatosis. In addition, it has been proposed that cell priming or gene transduction can be novel strategies for the development of next-generation high-efficacy MSCs for treating inflammatory skin diseases. We discuss here existing evidence that demonstrates the regulatory properties of MSCs on immune responses under inflammatory conditions.

Is depression an inflammatory condition? A review of available evidence.

PubMed

Hashmi, Ali Madeeh; Butt, Zeeshan; Umair, Muhammad

2013-07-01

The current review examines the relationship between depression and the inflammatory immune response. Mood disorders are a significant cause of morbidity and the etiology of depression is still not clearly understood. Many studies have shown links between inflammatory cytokines and mood disorders, including elevated level of cytokines like tumour necrosis factor-alpha (TNF alpha), Interleukins (IL-1,IL-6) and others. Raised levels of cytokines have been shown to increase depressive behaviour in animal models, while many anti-depressants reverse this behaviour alongside reducing the Central Nervous System (CNS) inflammatory response and reduction in the amounts of inflammatory cytokines. Cytokines reduce neurogenesis, Brain Derived Neurotrophic Factor (BDNF) and neuronal plasticity in the CNS, while many anti-depressants have been shown to reverse these processes. The considerations of anti-depressants as anti-inflammatory agents, and implication of other anti-inflammatory therapeutics for the treatment of depression are pointed out.

Successful treatment of generalized refractory chronic periodontitis through discontinuation of waxed or coated dental floss use: A report of 4 cases.

PubMed

Kelekis-Cholakis, Anastasia; Perry, John B; Pfeffer, Lorraine; Millete, Amy

2016-12-01

Generalized refractory chronic periodontitis is a periodontal condition that is resistant to conventional therapy. Management of this condition often is frustrating to both the patient and the clinician. The authors present 4 cases of generalized refractory chronic periodontitis characterized by an inflammatory gingival response and progressive bone loss that did not respond to extensive periodontal treatments and regular periodontal care. Histologic examination of affected gingival tissue revealed an abundance of plasma cells, a feature seen in certain oral contact hypersensitivity reactions. The authors suspected that waxed or coated dental floss was the offending contactant, and its removal from the patients' oral hygiene regimens resulted in a dramatic improvement of the periodontal characteristics. In cases of periodontal disease as described in this report, dental practitioners should consider the possibility of a contact hypersensitivity reaction to waxed or coated dental floss, whereby the floss exacerbates the condition instead of assisting in its resolution. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

A minocycline-releasing PMMA system as a space maintainer for staged bone reconstructions-in vitro antibacterial, cytocompatibility and anti-inflammatory characterization.

PubMed

Silva, Tiago; Grenho, Liliana; Barros, Joana; Silva, José Carlos; Pinto, Rosana V; Matos, Ana; Colaço, Bruno; Fernandes, Maria Helena; Bettencourt, Ana; Gomes, Pedro S

2017-06-06

In the present work, we study the development and biological characterization of a polymethyl methacrylate (PMMA)-based minocycline delivery system, to be used as a space maintainer within craniofacial staged regenerative interventions. The developed delivery systems were characterized regarding solid state characteristics and assayed in vitro for antibacterial and anti-inflammatory activity, and cytocompatibility with human bone cells. A drug release profile allowed for an initial burst release and a more sustained and controlled release over time, with minimum inhibitory concentrations for the assayed and relevant pathogenic bacteria (i.e., Staphylococcus aureus, slime-producer Staphylococcus epidermidis and Escherichia coli) being easily attained in the early time points, and sustained up to 72 h. Furthermore, an improved osteoblastic cell response-with enhancement of cell adhesion and cell proliferation-and increased anti-inflammatory activity were verified in developed systems, compared to a control (non minocycline-loaded PMMA cement). The obtained results converge to support the possible efficacy of the developed PMMA-based minocycline delivery systems for the clinical management of complex craniofacial trauma. Here, biomaterials with space maintenance properties are necessary for the management of staged reconstructive approaches, thus minimizing the risk of peri-operative infections and enhancing the local tissue healing and early stages of regeneration.

Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

PubMed

Tyler, Andrea D; Kirsch, Richard; Milgrom, Raquel; Stempak, Joanne M; Kabakchiev, Boyko; Silverberg, Mark S

2016-04-01

Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis. Microbial 16S rRNA was sequenced using the Illumina MiSeq platform. We observed a great deal of variability in the microbiome characterizing different sampling locations. Samples from pouch and afferent limb were comparable in microbial composition. When comparing sigmoid and terminal ileum samples, more differences were observed. The greatest number of differentially abundant microbes was observed when comparing either pouch or afferent limb samples to sigmoid or terminal ileum. Despite these differences, we were able to observe modest microbial variability between inflammatory bowel disease phenotypes and HCs, even when controlling for sampling location and additional experimental factors. Most detected associations were observed between HCs and Crohn's disease, with decreases in specific genera in the families Ruminococcaceae and Lachnospiraceae characterizing tissue samples from individuals with Crohn's disease. This study highlights important considerations when analyzing the composition of the microbiome and also provides useful insight into differences in the microbiome characterizing these seemingly related phenotypes.

Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atay, Safinur; Gercel-Taylor, Cicek; Kesimer, Mehmet

Exosomes represent an important intercellular communication vehicle, mediating events essential for the decidual microenvironment. While we have demonstrated exosome induction of pro-inflammatory cytokines, to date, no extensive characterization of trophoblast-derived exosomes has been provided. Our objective was to provide a morphologic and proteomic characterization of these exosomes. Exosomes were isolated from the conditioned media of Swan71 human trophoblast cells by ultrafiltration and ultracentrifugation. These were analyzed for density (sucrose density gradient centrifugation), morphology (electron microscopy), size (dynamic light scattering) and protein composition (Ion Trap mass spectrometry and western immunoblotting). Based on density gradient centrifugation, microvesicles from Sw71 cells exhibit amore » density between 1.134 and 1.173 g/ml. Electron microscopy demonstrated that microvesicles from Sw71 cells exhibit the characteristic cup-shaped morphology of exosomes. Dynamic light scattering showed a bell-shaped curve, indicating a homogeneous population with a mean size of 165 nm {+-} 0.5 nm. Ion Trap mass spectrometry demonstrated the presence of exosome marker proteins (including CD81, Alix, cytoskeleton related proteins, and Rab family). The MS results were confirmed by western immunoblotting. Based on morphology, density, size and protein composition, we defined the release of exosomes from extravillous trophoblast cells and provide their first extensive characterization. This characterization is essential in furthering our understanding of 'normal' early pregnancy.« less

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

PubMed Central

Jison, Maria L.; Munson, Peter J.; Barb, Jennifer J.; Suffredini, Anthony F.; Talwar, Shefali; Logun, Carolea; Raghavachari, Nalini; Beigel, John H.; Shelhamer, James H.; Danner, Robert L.; Gladwin, Mark T.

2016-01-01

In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury. PMID:15031206

A review of the application of inflammatory biomarkers in epidemiologic cancer research

PubMed Central

Brenner, Darren R.; Scherer, Dominique; Muir, Kenneth; Schildkraut, Joellen; Boffetta, Paolo; Spitz, Margaret R.; LeMarchand, Loic; Chan, Andrew T.; Goode, Ellen L.; Ulrich, Cornelia M.; Hung, Rayjean J.

2014-01-01

Inflammation is a facilitating process for multiple cancer types. It is believed to affect cancer development and progression through several etiologic pathways including increased levels of DNA adduct formation, increased angiogenesis and altered anti-apoptotic signaling. This review highlights the application of inflammatory biomarkers in epidemiologic studies and discusses the various cellular mediators of inflammation characterizing the innate immune system response to infection and chronic insult from environmental factors. Included is a review of six classes of inflammation-related biomarkers: cytokines/chemokines, immune-related effectors, acute phase proteins, reactive oxygen and nitrogen species, prostaglandins and cyclooxygenase-related factors, and mediators such as transcription factors and growth factors. For each of these biomarkers we provide a brief overview of the etiologic role in the inflammation response and how they have been related to cancer etiology and progression within the literature. We provide a discussion of the common techniques available for quantification of each marker including strengths, weaknesses and potential pitfalls. Subsequently, we highlight a few under-studied measures to characterize the inflammatory response and their potential utility in epidemiologic studies of cancer. Finally, we suggest integrative methods for future studies to apply multi-faceted approaches to examine the relationship between inflammatory markers and their roles in cancer development. PMID:24962838

Cytotoxic and Inflammatory Potential of Air Samples from Occupational Settings with Exposure to Organic Dust

PubMed Central

Viegas, Susana; Caetano, Liliana Aranha; Korkalainen, Merja; Faria, Tiago; Pacífico, Cátia; Carolino, Elisabete; Quintal Gomes, Anita; Viegas, Carla

2017-01-01

Organic dust and related microbial exposures are the main inducers of several respiratory symptoms. Occupational exposure to organic dust is very common and has been reported in diverse settings. In vitro tests using relevant cell cultures can be very useful for characterizing the toxicity of complex mixtures present in the air of occupational environments such as organic dust. In this study, the cell viability and the inflammatory response, as measured by the production of pro-inflammatory cytokines tumor necrosis factor-α (TNFα) and interleukin-1 β (IL-1β), were determined in human macrophages derived from THP-1 monocytic cells. These cells were exposed to air samples from five occupational settings known to possess high levels of contamination of organic dust: poultry and swine feed industries, waste sorting, poultry production and slaughterhouses. Additionally, fungi and particle contamination of those settings was studied to better characterize the organic dust composition. All air samples collected from the assessed workplaces caused both cytotoxic and pro-inflammatory effects. The highest responses were observed in the feed industry, particularly in swine feed production. This study emphasizes the importance of measuring the organic dust/mixture effects in occupational settings and suggests that differences in the organic dust content may result in differences in health effects for exposed workers. PMID:29051440

"Characterization of the immune reagent chicken IL-16"

USDA-ARS?s Scientific Manuscript database

Interleukin-16 has been characterized as a pro-inflammatory cytokine that mediates an immune response in human and mouse monocytes and peripheral blood mononuclear cells (PBMC), and it plays a role in proliferating B-cells and myelomas. The function of chicken IL-16 ortholog (ch-IL-16) is far less u...

Berberine Improves Intestinal Motility and Visceral Pain in the Mouse Models Mimicking Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D) Symptoms in an Opioid-Receptor Dependent Manner

PubMed Central

Pan, Qiuhui; Fichna, Jakub; Zheng, Lijun; Wang, Kesheng; Yu, Zhen; Li, Yongyu; Li, Kun; Song, Aihong; Liu, Zhongchen; Song, Zhenshun; Kreis, Martin

2015-01-01

Background and Aims Berberine and its derivatives display potent analgesic, anti-inflammatory and anticancer activity. Here we aimed at characterizing the mechanism of action of berberine in the gastrointestinal (GI) tract and cortical neurons using animal models and in vitro tests. Methods The effect of berberine was characterized in murine models mimicking diarrhea-predominant irritable bowel syndrome (IBS-D) symptoms. Then the opioidantagonists were used to identify the receptors involved. Furthermore, the effect of berberineon opioid receptors expression was established in the mouse intestine and rat fetal cortical neurons. Results In mouse models, berberine prolonged GI transit and time to diarrhea in a dose-dependent manner, and significantly reduced visceral pain. In physiological conditions the effects of berberine were mediated by mu- (MOR) and delta- (DOR) opioidreceptors; hypermotility, excessive secretion and nociception were reversed by berberine through MOR and DOR-dependent action. We also found that berberine increased the expression of MOR and DOR in the mouse bowel and rat fetal cortical neurons. Conclusion Berberine significantly improved IBS-D symptoms in animal models, possibly through mu- and delta- opioid receptors. Berberine may become a new drug candidate for the successful treatment of IBS-D in clinical conditions. PMID:26700862

Human conditions of insulin-like growth factor-I (IGF-I) deficiency

PubMed Central

2012-01-01

Insulin-like growth factor I (IGF-I) is a polypeptide hormone produced mainly by the liver in response to the endocrine GH stimulus, but it is also secreted by multiple tissues for autocrine/paracrine purposes. IGF-I is partly responsible for systemic GH activities although it possesses a wide number of own properties (anabolic, antioxidant, anti-inflammatory and cytoprotective actions). IGF-I is a closely regulated hormone. Consequently, its logical therapeutical applications seems to be limited to restore physiological circulating levels in order to recover the clinical consequences of IGF-I deficiency, conditions where, despite continuous discrepancies, IGF-I treatment has never been related to oncogenesis. Currently the best characterized conditions of IGF-I deficiency are Laron Syndrome, in children; liver cirrhosis, in adults; aging including age-related-cardiovascular and neurological diseases; and more recently, intrauterine growth restriction. The aim of this review is to summarize the increasing list of roles of IGF-I, both in physiological and pathological conditions, underlying that its potential therapeutical options seem to be limited to those proven states of local or systemic IGF-I deficiency as a replacement treatment, rather than increasing its level upper the normal range. PMID:23148873

Surface Acoustic Wave (SAW) Resonators for Monitoring Conditioning Film Formation

PubMed Central

Hohmann, Siegfried; Kögel, Svea; Brunner, Yvonne; Schmieg, Barbara; Ewald, Christina; Kirschhöfer, Frank; Brenner-Weiß, Gerald; Länge, Kerstin

2015-01-01

We propose surface acoustic wave (SAW) resonators as a complementary tool for conditioning film monitoring. Conditioning films are formed by adsorption of inorganic and organic substances on a substrate the moment this substrate comes into contact with a liquid phase. In the case of implant insertion, for instance, initial protein adsorption is required to start wound healing, but it will also trigger immune reactions leading to inflammatory responses. The control of the initial protein adsorption would allow to promote the healing process and to suppress adverse immune reactions. Methods to investigate these adsorption processes are available, but it remains difficult to translate measurement results into actual protein binding events. Biosensor transducers allow user-friendly investigation of protein adsorption on different surfaces. The combination of several transduction principles leads to complementary results, allowing a more comprehensive characterization of the adsorbing layer. We introduce SAW resonators as a novel complementary tool for time-resolved conditioning film monitoring. SAW resonators were coated with polymers. The adsorption of the plasma proteins human serum albumin (HSA) and fibrinogen onto the polymer-coated surfaces were monitored. Frequency results were compared with quartz crystal microbalance (QCM) sensor measurements, which confirmed the suitability of the SAW resonators for this application. PMID:26007735

Emotional Processes in Patients Undergoing Coronary Artery Bypass Graft Surgeries with Extracorporeal Circulation in View of Selected Indicators of the Inflammatory Condition

PubMed Central

Płotek, Włodzimierz; Pielok, Joanna; Cybulski, Marcin; Samborska, Regina

2015-01-01

Background The aim of this study was to describe positive and negative emotions in patients undergoing coronary artery bypass graft (CABG) surgeries with extracorporeal circulation and the correlations between emotions and basic indicators of the inflammatory condition: C-reactive protein (CRP) concentration, body temperature, and leukocyte count. Material/Methods Standardized tools were used to select 52 patients (aged 47–63 years, 6 women – 11.5% and 46 men – 88.5%) without dementia or depression. The Positive and Negative Affect Schedule (PANAS) was used to examine positive affect (PA) and negative affect (NA) and the State-Trait Anxiety Inventory (STAI X1 and X2) was used to examine the anxiety level. The patients underwent CABG surgery according to a common anesthesia protocol and for 5 consecutive days they were observed in the ward, where selected indicators of the inflammatory condition were monitored. Results A detailed description of the results of examinations of emotions was presented. The patients with low PA-trait level, high NA-trait level, and high anxiety-trait level (STAI X2) exhibited statistically significantly higher body temperatures than the other patients in the postoperative period. The patients with high NA-trait and anxiety-state levels (STAI X1) had statistically significantly lower CRP levels in the postoperative period than the patients with low NA-trait and anxiety-state levels (STAI X1). Conclusions Patients undergoing CABG operations express both positive and negative affects. The changes in the inflammatory markers are expressed mostly by CRP concentration. There exist relationships between the result of tests assessing emotions and the markers of the inflammatory condition. PMID:25573296

Burden of major musculoskeletal conditions.

PubMed Central

Woolf, Anthony D.; Pfleger, Bruce

2003-01-01

Musculoskeletal conditions are a major burden on individuals, health systems, and social care systems, with indirect costs being predominant. This burden has been recognized by the United Nations and WHO, by endorsing the Bone and Joint Decade 2000-2010. This paper describes the burden of four major musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, osteoporosis, and low back pain. Osteoarthritis, which is characterized by loss of joint cartilage that leads to pain and loss of function primarily in the knees and hips, affects 9.6% of men and 18% of women aged > 60 years. Increases in life expectancy and ageing populations are expected to make osteoarthritis the fourth leading cause of disability by the year 2020. Joint replacement surgery, where available, provides effective relief. Rheumatoid arthritis is an inflammatory condition that usually affects multiple joints. It affects 0.3-1.0% of the general population and is more prevalent among women and in developed countries. Persistent inflammation leads to joint destruction, but the disease can be controlled with drugs. The incidence may be on the decline, but the increase in the number of older people in some regions makes it difficult to estimate future prevalence. Osteoporosis, which is characterized by low bone mass and microarchitectural deterioration, is a major risk factor for fractures of the hip, vertebrae, and distal forearm. Hip fracture is the most detrimental fracture, being associated with 20% mortality and 50% permanent loss in function. Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at some point in time and about 4-33% of the population at any given point. Cultural factors greatly influence the prevalence and prognosis of low back pain. PMID:14710506

Pinosylvin and monomethylpinosylvin, constituents of an extract from the knot of Pinus sylvestris, reduce inflammatory gene expression and inflammatory responses in vivo.

PubMed

Laavola, Mirka; Nieminen, Riina; Leppänen, Tiina; Eckerman, Christer; Holmbom, Bjarne; Moilanen, Eeva

2015-04-08

Scots pine (Pinus sylvestris) is known to be rich in phenolic compounds, which may have anti-inflammatory properties. The present study investigated the anti-inflammatory effects of a knot extract from P. sylvestris and two stilbenes, pinosylvin and monomethylpinosylvin, isolated from the extract. Inflammation is characterized by increased release of pro-inflammatory and regulatory mediators including nitric oxide (NO) produced by the inducible nitric oxide synthase (iNOS) pathway. The knot extract (EC50 values of 3 and 3 μg/mL) as well as two of its constituents, pinosylvin (EC50 values of 13 and 15 μM) and monomethylpinosylvin (EC50 values of 8 and 12 μM), reduced NO production and iNOS expression in activated macrophages. They also inhibited the production of inflammatory cytokines IL-6 and MCP-1. More importantly, pinosylvin and monomethylpinosylvin exerted a clear anti-inflammatory effect (80% inhibition at the dose of 100 mg/kg) in the standard in vivo model, carrageenan-induced paw inflammation in the mouse, with the effect being comparable to that of a known iNOS inhibitor L-NIL. The results reveal that the Scots pine stilbenes pinosylvin and monomethylpinosylvin are potential anti-inflammatory compounds.

Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

PubMed Central

Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

2015-01-01

Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease. PMID:26247971

Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

PubMed

Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

2015-08-04

Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

Evaluation of the effect of the degree of acetylation on the inflammatory response to 3D porous chitosan scaffolds.

PubMed

Barbosa, Judite N; Amaral, Isabel F; Aguas, Artur P; Barbosa, Mário A

2010-04-01

The effect of the degree of acetylation (DA) of 3D chitosan (Ch) scaffolds on the inflammatory reaction was investigated. Chitosan porous scaffolds with DAs of 4 and 15% were implanted using a subcutaneous air-pouch model of inflammation. The initial acute inflammatory response was evaluated 24 and 48 h after implantation. To characterize the initial response, the recruitment and adhesion of inflammatory cells to the implant site was studied. The fibrous capsule formation and the infiltration of inflammatory cells within the scaffolds were evaluated for longer implantation times (2 and 4 weeks). Chitosan with DA 15% attracted the highest number of leukocytes to the implant site. High numbers of adherent inflammatory cells were also observed in this material. For longer implantation periods Ch scaffolds with a DA of 15% induced the formation of a thick fibrous capsule and a high infiltration of inflammatory cells within the scaffold. Our results indicate that the biological response to implanted Ch scaffolds was influenced by the DA. Chitosan with a DA of 15% induce a more intense inflammatory response when compared with DA 4% Ch. Because inflammation and healing are interrelated, this result may provide clues for the relative importance of acetyl and amine functional groups in tissue repair and regeneration.

Extracorporeal membrane oxygenation and cytokine adsorption

PubMed Central

Träger, Karl

2018-01-01

Extracorporeal membrane oxygenation (ECMO) is an increasingly used technology for mechanical support of respiratory and cardio-circulatory failure. Excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. The overwhelming inflammatory response is characterized by highly elevated pro- and anti-inflammatory cytokine levels. The excessive cytokine release during the overwhelming inflammatory response may result in multiple organ damage and failure. During ECMO therapy activation of complement and contact systems occur which may be followed by cytokine release. Controlling excessively increased cytokines may be considered as a valuable treatment option. Hemoadsorption therapy may be used to decrease cytokine levels in case of excessive inflammatory response and due to its unspecific adsorptive characteristics also substances like myoglobin, free hemoglobin or bilirubin. Controlling pro-inflammatory response with hemoadsorption may have positive impact on the endothelial glycocalix and also may be advantageous for maintenance of the vascular barrier function which plays a pivotal role in the development of tissue edema and oxygen mismatch. Hemoadsorption therapy seems to offer a promising new option for the treatment of patients with overwhelming inflammatory response leading to faster hemodynamic and metabolic stabilization finally resulting in preserved organ functions. PMID:29732183

Extracorporeal membrane oxygenation and cytokine adsorption.

PubMed

Datzmann, Thomas; Träger, Karl

2018-03-01

Extracorporeal membrane oxygenation (ECMO) is an increasingly used technology for mechanical support of respiratory and cardio-circulatory failure. Excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. The overwhelming inflammatory response is characterized by highly elevated pro- and anti-inflammatory cytokine levels. The excessive cytokine release during the overwhelming inflammatory response may result in multiple organ damage and failure. During ECMO therapy activation of complement and contact systems occur which may be followed by cytokine release. Controlling excessively increased cytokines may be considered as a valuable treatment option. Hemoadsorption therapy may be used to decrease cytokine levels in case of excessive inflammatory response and due to its unspecific adsorptive characteristics also substances like myoglobin, free hemoglobin or bilirubin. Controlling pro-inflammatory response with hemoadsorption may have positive impact on the endothelial glycocalix and also may be advantageous for maintenance of the vascular barrier function which plays a pivotal role in the development of tissue edema and oxygen mismatch. Hemoadsorption therapy seems to offer a promising new option for the treatment of patients with overwhelming inflammatory response leading to faster hemodynamic and metabolic stabilization finally resulting in preserved organ functions.

Molecular inflammation as an underlying mechanism of the aging process and age-related diseases.

PubMed

Chung, H Y; Lee, E K; Choi, Y J; Kim, J M; Kim, D H; Zou, Y; Kim, C H; Lee, J; Kim, H S; Kim, N D; Jung, J H; Yu, B P

2011-07-01

Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism's pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.

Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis.

PubMed

Bermudez, Maria A; Sendon-Lago, Juan; Seoane, Samuel; Eiro, Noemi; Gonzalez, Francisco; Saa, Jorge; Vizoso, Francisco; Perez-Fernandez, Roman

2016-08-01

The aim of the present study was to evaluate the effect of conditioned medium from human uterine cervical stem cells (CM-hUCESCs) in uveitis. To do that, uveitis was induced in rats after footpad injection of Escherichia coli lipopolysaccaride (LPS). Human retinal pigment epithelial (ARPE-19) cells after LPS challenge were used to test anti-inflammatory effect of CM-hUCESCs 'ìn vitro'. Real-time PCR was used to evaluate mRNA expression levels of the pro-inflammatory cytokines interkeukin-6, interkeukin-8, macrophage inflammatory protein-1 alpha, tumor necrosis factor alpha, and the anti-inflammatory interkeukin-10. Leucocytes from aqueous humor (AqH) were quantified in a Neubauer chamber, and eye histopathological analysis was done with hematoxylin-eosin staining. Additionally, using a human cytokine antibody array we evaluated CM-hUCESCs to determine mediating proteins. Results showed that administration of CM-hUCESCs significantly reduced LPS-induced pro-inflammatory cytokines both 'in vitro' and 'in vivo', and decreased leucocytes in AqH and ocular tissues. High levels of cytokines with anti-inflammatory effects were found in CM-hUCESCs, suggesting a possible role of these factors in reducing intraocular inflammation. In summary, treatment with CM-hUCESCs significantly reduces inflammation in uveitis. Our data indicate that CM-hUCESCs could be regarded as a potential therapeutic agent for patients suffering from ocular inflammation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spondias tuberosa (Anacardiaceae) leaves: profiling phenolic compounds by HPLC-DAD and LC-MS/MS and in vivo anti-inflammatory activity.

PubMed

da Silva Siqueira, Emerson Michell; Félix-Silva, Juliana; de Araújo, Lorena Maria Lima; Fernandes, Julia Morais; Cabral, Bárbara; Gomes, Jacyra Antunes Dos Santos; de Araújo Roque, Alan; Tomaz, José Carlos; Lopes, Norberto Peporine; de Freitas Fernandes-Pedrosa, Matheus; Giordani, Raquel Brandt; Zucolotto, Silvana Maria

2016-10-01

Spondias tuberosa is a medicinal plant used by several local communities in northeast Brazil to treat infections, digestive disorders and inflammatory conditions. The study aimed to identify and quantify the major phenolic in hydroethanolic extract of leaves from S. tuberosa and to evaluate its anti-inflammatory potential. The chemical profile of extract was analyzed by HPLC-DAD and HPLC-MS. The in vivo anti-inflammatory activity was investigated in carrageenan-induced hind paw edema and peritonitis models in mice. Identified and quantified through HPLC-DAD or HPLC-MS analyses of S. tuberosa extract were the following compounds: chlorogenic acid, caffeic acid, rutin and isoquercitrin. The inflammatory response to carrageenan was significantly reduced in both models by S. tuberosa extract. In hind paw edema, the edematogenic response was reduced by up to 63.6% and the myeloperoxidase activity was completely inhibited. In the peritonitis model, the total cell migration into the peritoneal cavity was reduced by up to 65%. The results obtained give evidence of the anti-inflammatory action of S. tuberosa and suggest the potential therapeutic benefit of this plant on inflammatory conditions. The chlorogenic acid, caffeic acid, rutin and isoquercitrin identified and quantified in S. tuberosa leaves enable us to suggest that these compounds could be used as chemical markers for quality control of derivative products from this species. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

CC-chemokine class inhibition attenuates pathological angiogenesis while preserving physiological angiogenesis.

PubMed

Ridiandries, Anisyah; Tan, Joanne T M; Ravindran, Dhanya; Williams, Helen; Medbury, Heather J; Lindsay, Laura; Hawkins, Clare; Prosser, Hamish C G; Bursill, Christina A

2017-03-01

Increasing evidence shows that CC-chemokines promote inflammatory-driven angiogenesis, with little to no effect on hypoxia-mediated angiogenesis. Inhibition of the CC-chemokine class may therefore affect angiogenesis differently depending on the pathophysiological context. We compared the effect of CC-chemokine inhibition in inflammatory and physiological conditions. In vitro , the broad-spectrum CC-chemokine inhibitor "35K" inhibited inflammatory-induced endothelial cell proliferation, migration, and tubulogenesis, with more modest effects in hypoxia. In vivo , adenoviruses were used to overexpress 35K (Ad35K) and GFP (AdGFP, control virus). Plasma chemokine activity was suppressed by Ad35K in both models. In the periarterial femoral cuff model of inflammatory-driven angiogenesis, overexpression of 35K inhibited adventitial neovessel formation compared with control AdGFP-infused mice. In contrast, 35K preserved neovascularization in the hindlimb ischemia model and had no effect on physiological neovascularization in the chick chorioallantoic membrane assay. Mechanistically, 2 key angiogenic proteins (VEGF and hypoxia-inducible factor-1α) were conditionally regulated by 35K, such that expression was inhibited in inflammation but was unchanged in hypoxia. In conclusion, CC-chemokine inhibition by 35K suppresses inflammatory-driven angiogenesis while preserving physiological ischemia-mediated angiogenesis via conditional regulation of VEGF and hypoxia-inducible factor-1α. CC-chemokine inhibition may be an alternative therapeutic strategy for suppressing diseases associated with inflammatory angiogenesis without inducing the side effects caused by global inhibition.- Ridiandries, A., Tan, J. T. M., Ravindran, D., Williams, H., Medbury, H. J., Lindsay, L., Hawkins, C., Prosser, H. C. G., Bursill, C. A. CC-chemokine class inhibition attenuates pathological angiogenesis while preserving physiological angiogenesis. © FASEB.

Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation.

PubMed

Iwamoto, Tatsushige; Takasugi, Yoshihiro; Higashino, Hideaki; Ito, Hiroyuki; Koga, Yoshihisa; Nakao, Shinichi

2011-02-01

Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition. In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60 min after drug injection, the effective dose required to produce 50% response (ED(50)) of each drug was derived. Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED(50s) of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED(50s) of 1.006 pmol in intact rats and 0.310 pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats. These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats.

[Update on the use of PET radiopharmaceuticals in inflammatory disease].

PubMed

Martínez-Rodríguez, I; Carril, J M

2013-01-01

The use of molecular imaging with PET/CT technology using different radiotracers, especially the (18)F-FDG is currently spreading beyond the area of oncology, the most interest being placed on inflammatory and infectious diseases. This article presents a review of its contribution in different inflammatory conditions in the context of structural and conventional nuclear medicine imaging. Special emphasis is placed on the more significant diseases such as large-vessel vasculitis, sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of the atheroma plaque. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

[Immunometabolism of exercise and sedentary lifestyle].

PubMed

Moreno-Eutimio, Mario Adán; Acosta-Altamirano, Gustavo

2014-01-01

Sedentary lifestyle leads to the accumulation of visceral fat. This is accompanied by the infiltration of immune cells with pro-inflammatory characteristics in adipose tissue, causing an increased release of cytokines and generating a low-grade inflammatory state. It has been associated with the development of insulin resistance, atherosclerosis, neurodegeneration, and development of tumors. Exercise can be used as a treatment to improve symptoms of many of these conditions because it promotes an anti-inflammatory effect. In this review we analyze the pro-inflammatory factors present in obesity and the induction of antiinflammatory factors that occur with exercise.

Alternative RNA splicing of leucocyte tissue transglutaminase in coeliac disease.

PubMed

Arbildi, P; Sóñora, C; Del Río, N; Marqués, J M; Hernández, A

2018-05-01

Tissue transglutaminase is a ubiquitous and multifunctional protein that contributes to several processes such as apoptosis/survival, efferocytosis, inflammation and tissue repairing under physiological and pathological conditions. Several activities can be associated with well-established functional domains; in addition, four RNA alternative splice variants have been described, characterized by sequence divergences and residues deletion at the C-terminal domains. Tissue transglutaminase is recognized as the central player in the physiopathology of coeliac disease (CD) mainly through calcium-dependent enzymatic activities. It can be hypothesized that differential regulation of tissue transglutaminase splice variants expression in persons with CD contributes to pathology by altering the protein functionality. We characterized the expression pattern of RNA alternative splice variants by RT-PCR in peripheral cells from patients with CD under free gluten diet adhesion; we considered inflammatory parameters and specific antibodies as markers of the stage of disease. We found significant higher expression of both the full length and the shortest C-truncated splice variants in leucocytes from patients with CD in comparison with healthy individuals. As tissue transglutaminase expression and canonical enzymatic activity are linked to inflammation, we studied the RNA expression of inflammatory cytokines in peripheral leucocytes of persons with CD in relation with splice variants expression; interestingly, we found that recently diagnosed patients showed significant correlation between both the full length and the shortest alternative spliced variants with IL-1 expression. Our results points that regulation of alternative splicing of tissue transglutaminase could account for the complex physiopathology of CD. © 2018 The Foundation for the Scandinavian Journal of Immunology.

In vitro characterization of cutaneous immunotoxicity of immortalized human keratinocytes (HaCaT) exposed to reactive and disperse textile dyes.

PubMed

Leme, Daniela Morais; Sehr, Andrea; Grummt, Tamara; Gonçalves, Jenifer Pendiuk; Jacomasso, Thiago; Winnischofer, Sheila Maria Brochado; Potrich, Francine Bittencourt; Oliveira, Carolina Camargo de; Trindade, Edvaldo da Silva; de Oliveira, Danielle Palma

2018-05-01

Several synthetic dyes are used by textile industry for supplying the market of colored clothes. However, these chemicals have been associated with a variety of adverse human health effects, including textile dermatitis. Thus, there is a growing concern to identify textile dyes potentially as skin immunotoxicants. The aim of this in vitro study was to characterize the immunotoxic potential of reactive (Reactive Green 19 [RG19], Reactive Blue 2 [RB2], Reactive Black 5 [RB5]) and disperse (Disperse Red 1 [DR1]) textile dyes using a dermal cell line. For this purpose, a cell-based approach was conducted with immortalized human keratinocytes (KC) (HaCaT) using selected biomarkers of cutaneous inflammation including modulation of matrix metalloproteinases (MMP), oxidative stress such as reactive oxygen species (ROS) generation, and inflammatory cytokine profile. DR1 was the only dye able to trigger an immune response such as release of IL-12 cytokine, a potent co-stimulator of T helper 1 cell, which may be considered as a skin immunotoxicant. The reactive dyes including RB5 that were previously reported as skin sensitizers failed to induce inflammatory reactions under the conditions tested. The reactive dyes studied may pose a risk to human KC by induction of effects related to modulation of MMP-2 (RB5) and -9 (RB5 and RB2) and generation of ROS (RG19 and RB2). Thus, all these dyes need to be used with caution to avoid undesirable effects to consumers who may be exposed dermally.

Novel catalase loaded nanocores for the treatment of inflammatory bowel diseases.

PubMed

Parihar, Arun K S; Srivastava, Shikha; Patel, Satish; Singh, Manju R; Singh, Deependra

2017-08-01

Inflammatory bowel disease (IBD) is an inflammatory disorder of the digestive tract reported to be primarily caused by oxidative stress. In this study, alginate encapsulated nanoceramic carriers were designed to deliver acid labile antioxidant enzyme catalase orally. Complete system was characterized for size, loading efficiency, in vitro antioxidant assay and in vitro release. The prepared nanoceramic system was found to be spherical with diameter of 925 ± 6.81 nm. The in vitro release data followed the Higuchi model in acidic buffer whereas in alkaline pH sustained and almost first order release of enzyme was observed up to 6 h.

Dramatic response to alectinib in inflammatory myofibroblastic tumor with anaplastic lymphoma kinase fusion gene.

PubMed

Saiki, Masafumi; Ohyanagi, Fumiyoshi; Ariyasu, Ryo; Koyama, Junji; Sonoda, Tomoaki; Nishikawa, Shingo; Kitazono, Satoru; Yanagitani, Noriko; Horiike, Atsushi; Ninomiya, Hironori; Ishikawa, Yuichi; Nishio, Makoto

2017-12-01

Inflammatory myofibroblastic tumor (IMT) is a neoplasm characterized by the proliferaton of myofibroblasts with the infiltration of inflammatory cells. There is no standard treatment for patients with recurrent or metastatic IMT. We describe here a patient with hyper-progressive IMT with an anaplastic lymphoma kinase (ALK) fusion gene that dramatically responded to alectinib without adverse events. His dramatic and enduring response supports the observation that alectinib may be considered a good treatment option for rare aggressive ALK-positive tumors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain and Peripheral Atypical Inflammatory Mediators Potentiate Neuroinflammation and Neurodegeneration.

PubMed

Kempuraj, Duraisamy; Thangavel, Ramasamy; Selvakumar, Govindhasamy P; Zaheer, Smita; Ahmed, Mohammad E; Raikwar, Sudhanshu P; Zahoor, Haris; Saeed, Daniyal; Natteru, Prashant A; Iyer, Shankar; Zaheer, Asgar

2017-01-01

Neuroinflammatory response is primarily a protective mechanism in the brain. However, excessive and chronic inflammatory responses can lead to deleterious effects involving immune cells, brain cells and signaling molecules. Neuroinflammation induces and accelerates pathogenesis of Parkinson's disease (PD), Alzheimer's disease (AD) and Multiple sclerosis (MS). Neuroinflammatory pathways are indicated as novel therapeutic targets for these diseases. Mast cells are immune cells of hematopoietic origin that regulate inflammation and upon activation release many proinflammatory mediators in systemic and central nervous system (CNS) inflammatory conditions. In addition, inflammatory mediators released from activated glial cells induce neurodegeneration in the brain. Systemic inflammation-derived proinflammatory cytokines/chemokines and other factors cause a breach in the blood brain-barrier (BBB) thereby allowing for the entry of immune/inflammatory cells including mast cell progenitors, mast cells and proinflammatory cytokines and chemokines into the brain. These peripheral-derived factors and intrinsically generated cytokines/chemokines, α-synuclein, corticotropin-releasing hormone (CRH), substance P (SP), beta amyloid 1-42 (Aβ1-42) peptide and amyloid precursor proteins can activate glial cells, T-cells and mast cells in the brain can induce additional release of inflammatory and neurotoxic molecules contributing to chronic neuroinflammation and neuronal death. The glia maturation factor (GMF), a proinflammatory protein discovered in our laboratory released from glia, activates mast cells to release inflammatory cytokines and chemokines. Chronic increase in the proinflammatory mediators induces neurotoxic Aβ and plaque formation in AD brains and neurodegeneration in PD brains. Glial cells, mast cells and T-cells can reactivate each other in neuroinflammatory conditions in the brain and augment neuroinflammation. Further, inflammatory mediators from the brain can also enter into the peripheral system through defective BBB, recruit immune cells into the brain, and exacerbate neuroinflammation. We suggest that mast cell-associated inflammatory mediators from systemic inflammation and brain could augment neuroinflammation and neurodegeneration in the brain. This review article addresses the role of some atypical inflammatory mediators that are associated with mast cell inflammation and their activation of glial cells to induce neurodegeneration.

Coating and release of an anti-inflammatory hormone from PLGA microspheres for tissue engineering.

PubMed

Go, Dewi P; Palmer, Jason A; Gras, Sally L; O'Connor, Andrea J

2012-02-01

Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone α-melanocyte stimulating hormone (α-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory responses to this material. The stability and adsorption isotherm of peptide binding were characterized. The peptide secondary structure was not perturbed by the adsorption and subsequent desorption process. The α-MSH payload was released over 72 h and reduced the expression of the inflammatory cytokine, Tumor necrosis factor-α (TNF-α) in lipopolysaccharide activated RAW 264.7 macrophage cells, indicating that the biological activity of α-MSH was preserved. α-MSH coated PLGA microspheres also appeared to reduce the influx of inflammatory cells in a subcutaneous implantation model in rats. This study demonstrates the potential of α-MSH coatings for anti-inflammatory delivery and this approach may be applied to other tissue engineering applications. Copyright © 2011 Wiley Periodicals, Inc.

Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

PubMed

Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

2015-08-01

Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

Inflammatory signaling in human tuberculosis granulomas is spatially organized.

PubMed

Marakalala, Mohlopheni J; Raju, Ravikiran M; Sharma, Kirti; Zhang, Yanjia J; Eugenin, Eliseo A; Prideaux, Brendan; Daudelin, Isaac B; Chen, Pei-Yu; Booty, Matthew G; Kim, Jin Hee; Eum, Seok Yong; Via, Laura E; Behar, Samuel M; Barry, Clifton E; Mann, Matthias; Dartois, Véronique; Rubin, Eric J

2016-05-01

Granulomas are the pathological hallmark of tuberculosis (TB). However, their function and mechanisms of formation remain poorly understood. To understand the role of granulomas in TB, we analyzed the proteomes of granulomas from subjects with tuberculosis in an unbiased manner. Using laser-capture microdissection, mass spectrometry and confocal microscopy, we generated detailed molecular maps of human granulomas. We found that the centers of granulomas have a pro-inflammatory environment that is characterized by the presence of antimicrobial peptides, reactive oxygen species and pro-inflammatory eicosanoids. Conversely, the tissue surrounding the caseum has a comparatively anti-inflammatory signature. These findings are consistent across a set of six human subjects and in rabbits. Although the balance between systemic pro- and anti-inflammatory signals is crucial to TB disease outcome, here we find that these signals are physically segregated within each granuloma. From the protein and lipid snapshots of human and rabbit lesions analyzed here, we hypothesize that the pathologic response to TB is shaped by the precise anatomical localization of these inflammatory pathways during the development of the granuloma.

NSAIDs and Musculoskeletal Treatment: What is the Clinical Evidence?

ERIC Educational Resources Information Center

Stovitz, Steven D.; Johnson, Robert J.

2003-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for musculoskeletal injuries because the conditions are considered inflammatory in nature. However, because inflammation is a necessary component in healing, decreasing inflammation may be counterproductive. Also, many tendon injuries are, in fact, degenerative and not…

Blood vessel control of macrophage maturation promotes arteriogenesis in ischemia.

PubMed

Krishnasamy, Kashyap; Limbourg, Anne; Kapanadze, Tamar; Gamrekelashvili, Jaba; Beger, Christian; Häger, Christine; Lozanovski, Vladimir J; Falk, Christine S; Napp, L Christian; Bauersachs, Johann; Mack, Matthias; Haller, Hermann; Weber, Christian; Adams, Ralf H; Limbourg, Florian P

2017-10-16

Ischemia causes an inflammatory response that is intended to restore perfusion and homeostasis yet often aggravates damage. Here we show, using conditional genetic deletion strategies together with adoptive cell transfer experiments in a mouse model of hind limb ischemia, that blood vessels control macrophage differentiation and maturation from recruited monocytes via Notch signaling, which in turn promotes arteriogenesis and tissue repair. Macrophage maturation is controlled by Notch ligand Dll1 expressed in vascular endothelial cells of arteries and requires macrophage canonical Notch signaling via Rbpj, which simultaneously suppresses an inflammatory macrophage fate. Conversely, conditional mutant mice lacking Dll1 or Rbpj show proliferation and transient accumulation of inflammatory macrophages, which antagonizes arteriogenesis and tissue repair. Furthermore, the effects of Notch are sufficient to generate mature macrophages from monocytes ex vivo that display a stable anti-inflammatory phenotype when challenged with pro-inflammatory stimuli. Thus, angiocrine Notch signaling fosters macrophage maturation during ischemia.Molecular mechanisms of macrophage-mediated regulation of artery growth in response to ischemia are poorly understood. Here the authors show that vascular endothelium controls macrophage maturation and differentiation via Notch signaling, which in turn promotes arteriogenesis and ischemic tissue recovery.

Sustained, neuron-specific IKK/NF-κB activation generates a selective neuroinflammatory response promoting local neurodegeneration with aging

PubMed Central

2013-01-01

Background Increasing evidence indicates that neuroinflammation is a critical factor contributing to the progression of various neurodegenerative diseases. The IKK/NF-κB signalling system is a central regulator of inflammation, but it also affects neuronal survival and differentiation. A complex interplay between different CNS resident cells and infiltrating immune cells, which produce and respond to various inflammatory mediators, determines whether neuroinflammation is beneficial or detrimental. The IKK/NF-κB system is involved in both production of and responses to these mediators, although the precise contribution depends on the cell type as well as the cellular context, and is only partially understood. Here we investigated the specific contribution of neuronal IKK/NF-κB signalling on the regulation of neuroinflammatory processes and its consequences. To address this issue, we established and analysed a conditional gain-of-function mouse model that expresses a constitutively active allele of IKK2 in principal forebrain neurons (IKK2nCA). Proinflammatory gene and growth factor expression, histopathology, microgliosis, astrogliosis, immune cell infiltration and spatial learning were assessed at different timepoints after persistent canonical IKK2/NF-κB activation. Results In contrast to other cell types and organ systems, chronic IKK2/NF-κB signalling in forebrain neurons of adult IKK2nCA animals did not cause a full-blown inflammatory response including infiltration of immune cells. Instead, we found a selective inflammatory response in the dentate gyrus characterized by astrogliosis, microgliosis and Tnf-α upregulation. Furthermore, downregulation of the neurotrophic factor Bdnf correlated with a selective and progressive atrophy of the dentate gyrus and a decline in hippocampus-dependent spatial learning. Neuronal degeneration was associated with increased Fluoro-jade staining, but lacked activation of apoptosis. Remarkably, neuronal loss could be partially reversed when chronic IKK2/NF-κB signalling was turned off and Bdnf expression was restored. Conclusion Our results demonstrate that persistent IKK2/NF-κB signalling in forebrain neurons does not induce overall neuroinflammation, but elicits a selective inflammatory response in the dentate gyrus accompanied by decreased neuronal survival and impaired learning and memory. Our findings further suggest that chronic activation of neuronal IKK2/NF-κB signalling, possibly as a consequence of neuroinflammatory conditions, is able to induce apoptosis-independent neurodegeneration via paracrine suppression of Bdnf synthesis. PMID:24119288

Regioselective reaction: synthesis, characterization and pharmacological activity of some new Mannich and Schiff bases containing sydnone.

PubMed

Nithinchandra; Kalluraya, B; Aamir, S; Shabaraya, A R

2012-08-01

A novel series of 1-substituted aminomethyl-3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino-1,2,4-triazol-5-thiones (9), was prepared from the 3-[1-(4-isobutylphenyl)ethyl]-4-(3-aryl-4-sydnonylidene) amino 5-mercapto-1,2,4-triazoles (8) by aminomethylation with formaldehyde and secondary amine. The structures of Schiff bases (8) and Mannich bases (9) were characterized on the basis of IR, NMR, mass spectra1 data and elemental analysis. The newly synthesized compounds were screened for their anti-inflammatory and analgesic activities. Mannich bases (9) carrying piperidine and morpholine residues showed promising anti-inflammatory and analgesic activity. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pro-Inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents: A Review.

PubMed

Miłkowska, Paulina; Popko, Katarzyna; Demkow, Urszula; Wolańczyk, Tomasz

2017-04-30

Cytokines are a large group of small proteins which play a significant role in cell signaling and regulate a variety of processes in organisms, including proliferation and differentiation of many cells, mediation in defense reactions and regulation of hematopoiesis. Cytokines can be divided into those with pro- and those with anti-inflammatory properties. In the group of pro-inflammatory cytokines the most important are: IL-1 beta, IL-6, TNF-alpha, and IFN-gamma. Pro-inflammatory cytokines might be involved in the pathophysiology of many psychiatric conditions in adults, but their role in children and adolescents is less clear. The aim of this article is to demonstrate the patterns of pro-inflammatory cytokines in children and adolescents.

Pro-inflammatory Cytokines in Psychiatric Disorders in Children and Adolescents: A Review.

PubMed

Miłkowska, Paulina; Popko, Katarzyna; Demkow, Urszula; Wolańczyk, Tomasz

2017-01-01

Cytokines are a large group of small proteins which play a significant role in cell signaling and regulate a variety of processes in organisms, including proliferation and differentiation of many cells, mediation in defense reactions and regulation of hematopoiesis. Cytokines can be divided into those with pro- and those with anti-inflammatory properties. In the group of pro-inflammatory cytokines the most important are: IL-1 beta, IL-6, TNF-alpha, and IFN-gamma. Pro-inflammatory cytokines might be involved in the pathophysiology of many psychiatric conditions in adults, but their role in children and adolescents is less clear. The aim of this article is to demonstrate the patterns of pro-inflammatory cytokines in children and adolescents.

Potential Use of Food Protein-Derived Peptides in the Treatment of Inflammatory Diseases.

PubMed

Santiago-Lopez, Lourdes; Gonzalez-Cordova, Aaron F; Hernandez-Mendoza, Adrian; Vallejo-Cordoba, Belinda

2017-01-01

In recent years, major developments in the field of inflammatory pathophysiology have clearly shown that arthritis, diabetes, intestinal bowel diseases, and obesity, which affect many people around the world, are essentially inflammatory in nature. Different anti-inflammatory drugs have been used to treat these conditions. Some people are able to take these drugs without difficulty, yet others experience negative side effects. Hence, the search for new, natural anti-inflammatory alternatives has rapidly increased in recent years. Evidence has shown that food protein-derived peptides may be one alternative for treating inflammatory diseases. Peptides are encrypted in food proteins, can be released under hydrolysis conditions, and do not cause adverse effects. Despite limited information on the mechanism of action of peptides, in vitro and animal model studies have demonstrated their potential anti-inflammatory activity. Several in vitro studies have demonstrated that peptides can inhibit different pathways of inflammation processes such as that of the nuclear factor kappalight- chain of activated B cells (NF-κB). They can also induce the production of nitric oxide synthase (iNOs) and c-Jun N-terminal kinases (JNK) as well as influence PepT1 and CaRS, the transporters of peptides to the gastrointestinal tract that are responsible for the absorption of dietary peptides in the intestine. However, contradictory evidence has been reported in clinical assays. Hence, in this review, we present the latest research on the anti-inflammatory activity of food protein-derived peptides and provide future perspectives on the use of peptides as potential natural sources of therapeutic treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Groin pain and iliopsoas bursitis: always a cause-effect relationship?

PubMed

Di Sante, Luca; Paoloni, Marco; De Benedittis, Stefano; Tognolo, Lucrezia; Santilli, Valter

2014-01-01

Iliopsoas bursitis (IB) is characterized by inflammation and enlargement of the iliopsoas bursa. Although this condition is often associated with degenerative or inflammatory arthritis, infections, trauma, overuse and impingement syndromes, osteonecrosis and hip replacement, the pathogenesis of IB remains uncertain. We present a case report of IB associated with moderate hip osteoarthritis (HOA). We present a case report of a 73-year-old man with chronic left hip pain that did not respond to conservative treatments. An ultrasonography examination of the left hip revealed fluid-induced distension of the iliopsoas bursa, which was treated with aspiration followed by a corticosteroid-anesthetic injection. At the 30-day follow-up, despite an initial improvement in the patient's symptoms, both the pain and functional limitation returned, though not in association with bursa distension. The patient therefore underwent a total hip arthroplasty, which fully relieved the symptoms. We hypothesize that iliopsoas bursitis may, when associated with other pathological conditions, not be the only source of pain. It should, nevertheless, be considered for differential diagnosis purposes.

Penile Mondor's disease in a patient treated with radical chemoradiation for anal cancer

PubMed Central

Pittaka, Maria; Fotiou, Eleni; Dionysiou, Margarita; Polyviou, Petros; Eracleous, Eleni; Andreopoulos, Demetris

2017-01-01

Abstract Penile Mondor's disease is a rare condition characterized by sclerosing thrombophlebitis of the superficial dorsal penile vein. Usually its causes are benign, but it is also evident in cancer patients. We report the case of a 62-year-old man with a cT4 anal cancer (infiltration of corpora spongiosa and penile bulb), associated with extensive loco-regional lymphadenopathy, who developed painful lumps in the midline of the anterior penile surface while receiving radical chemoradiotherapy. Physical examination revealed two palpable cord-like swellings located 2 cm from the pubic symphysis. Color Doppler ultrasound established the diagnosis of Mondor's disease. The patient was successfully managed with non-steroidal anti-inflammatory drugs. The causative factors were pelvic malignancy and radiotherapy. The diagnosis was challenging since Mondor's disease is a rare condition and the differential diagnosis included malignancy progression. This is the first case report describing penile Mondor's disease in a patient with anal cancer under chemoradiotherapy. PMID:29383260

Pharmaceuticals and Stem Cells in Autism Spectrum Disorders: Wishful Thinking?

PubMed

Sivanesan, Senthilkumar; Tan, Aaron; Jeyaraj, Rebecca; Lam, James; Gole, Monica; Hardan, Antonio; Ashkan, Keyoumars; Rajadas, Jayakumar

2017-02-01

We provide a contemporary account of the key pathologic events pertaining to autism: the theory of oxidative stress and inflammatory causes, ideas of immune dysfunction, the probable biomarkers that can be used for diagnostics, and the use of pharmaceuticals and stem cells as possible candidates for the treatment of autism spectrum disorders (ASDs). ASDs are a group of complex neurodevelopmental conditions characterized by abnormal patterns of attention and impaired social and communication skills. ASDs are also associated with numerous functional challenges and potentially harmful deficits, including restricted and repetitive behaviors, anxiety, irritability, seizures, and self-harm. Although the exact causes of ASDs are unknown, it is suggested that genetic, epigenetic, and environmental factors play critical roles. More recent findings support evidence for synaptic defects and impairments in brain information processing that are linked to social and perceptual skills. Owing to the clinical heterogeneity and lack of precise diagnostic tools, current therapeutic approaches aimed at managing ASD-associated conditions are not definitive. Copyright © 2016 Elsevier Inc. All rights reserved.

When is irritable bowel syndrome not irritable bowel syndrome? Diagnosis and treatment of chronic functional abdominal pain.

PubMed

Grover, Madhusudan

2012-08-01

Functional abdominal pain syndrome (FAPS) is a distinct chronic gastrointestinal (GI) pain disorder characterized by the presence of constant or frequently recurring abdominal pain that is not associated with eating, change in bowel habits, or menstrual periods. The pain experience in FAPS is predominantly centrally driven as compared to other chronic painful GI conditions such as inflammatory bowel disease and chronic pancreatitis where peripherally acting factors play a major role in driving the pain. Psychosocial factors are often integrally associated with the disorder and can pose significant challenges to evaluation and treatment. Patients suffer from considerable loss of function, which can drive health care utilization. Treatment options are limited at best with most therapeutic regimens extrapolated from pain management of other functional GI disorders and chronic pain conditions. A comprehensive approach to management using a biopsychosocial construct and collaboration with pain specialists and psychiatry is most beneficial to the management of this disorder.

Monogenic Auto-inflammatory Syndromes: A Review of the Literature.

PubMed

Azizi, Gholamreza; Khadem Azarian, Shahin; Nazeri, Sepideh; Mosayebian, Ali; Ghiasy, Saleh; Sadri, Ghazal; Mohebi, Ali; Khan Nazer, Nikoo Hossein; Afraei, Sanaz; Mirshafiey, Abbas

2016-12-01

Auto-inflammatory syndromes are a new group of distinct hereditable disorders characterized by episodes of seemingly unprovoked inflammation (most commonly in skin, joints, gut, and eye), the absence of a high titer of auto-antibodies or auto-reactive T cells, and an inborn error of innate immunity. A narrative literature review was carried out of studies related to auto-inflammatory syndromes to discuss the pathogenesis and clinical manifestation of these syndromes. This review showed that the main monogenic auto-inflammatory syndromes are familial Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), Blau syndrome, TNF receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndrome (CAPS), and pyogenic arthritis with pyoderma gangrenosum and acne (PAPA). The data suggest that correct diagnosis and treatment of monogenic auto-inflammatory diseases relies on the physicians' awareness. Therefore, understanding of the underlying pathogenic mechanisms of auto-inflammatory syndromes, and especially the fact that these disorders are mediated by IL-1 secretion stimulated by monocytes and macrophages, facilitated significant progress in patient management.

In vitro and in vivo evaluation of the inflammatory potential of various nanoporous hydroxyapatite biomaterials.

PubMed

Velard, Frédéric; Schlaubitz, Silke; Fricain, Jean-Christophe; Guillaume, Christine; Laurent-Maquin, Dominique; Möller-Siegert, Janina; Vidal, Loïc; Jallot, Edouard; Sayen, Stéphanie; Raissle, Olivier; Nedelec, Jean-Marie; Vix-Guterl, Cathie; Anselme, Karine; Amédée, Joëlle; Laquerrière, Patrice

2015-01-01

To discriminate the most important physicochemical parameters for bone reconstruction, the inflammatory potential of seven nanoporous hydroxyapatite powders synthesized by hard or soft templating was evaluated both in vitro and in vivo. After physical and chemical characterization of the powders, we studied the production of inflammatory mediators by human primary monocytes after 4 and 24 h in contact with powders, and the host response after 2 weeks implantation in a mouse critical size defect model. In vitro results highlighted increases in the secretion of TNF-α, IL-1, -8, -10 and proMMP-2 and -9 and decreases in the secretion of IL-6 only for powders prepared by hard templating. In vivo observations confirmed an extensive inflammatory tissue reaction and a strong resorption for the most inflammatory powder in vitro. These findings highlight that the most critical physicochemical parameters for these nanoporous hydroxyapatite are, the crystallinity that controls dissolution potential, the specific surface area and the size and shape of crystallites.

Insights into Neuroinflammation in Parkinson's Disease: From Biomarkers to Anti-Inflammatory Based Therapies.

PubMed

Rocha, Natália Pessoa; de Miranda, Aline Silva; Teixeira, Antônio Lúcio

2015-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide, being characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Among several putative factors that may contribute to PD pathogenesis, inflammatory mechanisms may play a pivotal role. The involvement of microglial activation as well as of brain and peripheral immune mediators in PD pathophysiology has been reported by clinical and experimental studies. These inflammatory biomarkers evaluated by imaging techniques and/or by biological sample analysis have become valuable tools for PD diagnosis and prognosis. Regardless of the significant increase in the number of people suffering from PD, there are still no established disease-modifying or neuroprotective therapies for it. There is growing evidence of protective effect of anti-inflammatory drugs on PD development. Herein, we reviewed the current literature regarding the central nervous system and peripheral immune biomarkers in PD and advances in diagnostic and prognostic tools as well as the neuroprotective effects of anti-inflammatory therapies.

Conserved gene regulation during acute inflammation between zebrafish and mammals

PubMed Central

Forn-Cuní, G.; Varela, M.; Pereiro, P.; Novoa, B.; Figueras, A.

2017-01-01

Zebrafish (Danio rerio), largely used as a model for studying developmental processes, has also emerged as a valuable system for modelling human inflammatory diseases. However, in a context where even mice have been questioned as a valid model for these analysis, a systematic study evaluating the reproducibility of human and mammalian inflammatory diseases in zebrafish is still lacking. In this report, we characterize the transcriptomic regulation to lipopolysaccharide in adult zebrafish kidney, liver, and muscle tissues using microarrays and demonstrate how the zebrafish genomic responses can effectively reproduce the mammalian inflammatory process induced by acute endotoxin stress. We provide evidence that immune signaling pathways and single gene expression is well conserved throughout evolution and that the zebrafish and mammal acute genomic responses after lipopolysaccharide stimulation are highly correlated despite the differential susceptibility between species to that compound. Therefore, we formally confirm that zebrafish inflammatory models are suited to study the basic mechanisms of inflammation in human inflammatory diseases, with great translational impact potential. PMID:28157230

Natural Products: Insights into Leishmaniasis Inflammatory Response

PubMed Central

Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

2015-01-01

Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

[Dermatological features of auto-inflammatory recurrent fevers].

PubMed

Escudier, A; Mauvais, F-X; Bastard, P; Boussard, C; Jaoui, A; Koskas, V; Lecoq, E; Michel, A; Orcel, M-C; Truelle, P-E; Wohrer, D; Piram, M

2018-02-01

Auto-inflammatory diseases are characterized by unexplained and recurrent attacks of systemic inflammation often involving the skin, joints, or serosal membranes. They are due to a dysfunction or dysregulation of the innate immunity, which is the first line of defense against pathogens. Early recognition of these diseases by the clinician, especially by pediatricians encountering such pathologies in pediatric patients, is primordial to avoid complications. Skin manifestations, common in most auto-inflammatory diseases, are helpful for prompt diagnosis. After a brief physiopathological review, we will describe auto-inflammatory recurrent fevers by their main dermatological presentations: urticarial lesions, neutrophilic dermatoses, panniculitis, other maculopapular eruptions, dyskeratosis, skin vasculitis, and oral aphthous. We finally suggest a decision tree to help clinicians better target genetic exams in patients with recurrent fevers and dermatological manifestations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dehydrated Basella alba Fruit Juice as a Novel Natural Colorant: Pigment Stability, In Vivo Food Safety Evaluation and Anti-Inflammatory Mechanism Characterization.

PubMed

Huang, Fu-Long; Chiou, Robin Y-Y; Chen, Wei-Cheng; Ko, Huey-Jiun; Lai, Li-Jung; Lin, Shu-Mei

2016-09-01

Flesh of Basella alba L. mature fruits bearing deep-violet juice provides a novel and potential source of natural colorant. To minimize the pigment purification process and warrant safety acceptability, B. alba colorant powder (BACP) was prepared using mature fruits through a practical batch preparation and subjected to fundamental pigment characterization, food safety assessment and bio-function evaluation. Yield of the dehydrated B. alba colorant powder (BACP) was 37 g/kg fresh fruits. Reconstituted aqueous solution of the BACP exhibited an identical visible spectrum (400-700 nm) as that of fresh juice. Color of the solution (absorbance at 540 nm) was stable in a broad pH ranged from 3 to 8 and enhanced by co-presence of calcium and magnesium ions, while was rapidly bleached by ferrous and ferric ions. For in vivo food safety evaluation, ICR mice were daily gavage administered with BACP up to 1000 mg/kg body weight for 28 days. Organ weight determination, serum biochemical analysis and histopathological examination of hearts, livers, lungs and kidneys revealed no obvious health hazard. In vitro anti-inflammatory activity of BACP was characterized in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. BACP exerted potent anti-inflammatory activity by down-regulation of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), TNF-α, IL-1β, IL-6 and IL-12 and the blockage of IκB kinase (IKK)/IκB/nuclear factor-κ B (NFκB) activation cascade. These results supported that BACP may serve as a beneficial alternative of natural food colorant.

Poly(anhydride-co-imides): in vivo biocompatibility in a rat model.

PubMed

Ibim, S M; Uhrich, K E; Bronson, R; El-Amin, S F; Langer, R S; Laurencin, C T

1998-05-01

The degradation and tissue compatibility characteristics of a novel class of biodegradable poly(anhydride-co-imide) polymers: poly[trimellitylimidoglycine-co-1,6-bis(carboxyphenoxy)hexan e] (TMA-gly: CPH) (in 10:90; 30:70 and 50: 50 molar ratios) and poly[pyromellitylimidoalanine-co-1,6-bis(carboxyphenoxy)hexa ne] (PMA-ala:CPH) (in 10:90 and 30:70 molar ratios) were investigated and compared with control poly(lactic acid/glycolic acid) (PLAGA in 50:50 molar ratio) matrices, a well-characterized biocompatible polymer, in rat subcutaneous tissues for 60 days. Polymers were compression-molded into circular discs of 14 mm x 1 mm in diameter. On post-operative days 7, 14, 28 and 60, histological tissue samples were removed, prepared by fixation and staining, and analyzed by light microscopy. PLAGA matrices produced mild inflammatory reactions and were completely degraded at the end of 60 days, leaving implant tissues that were similar to surgical wounds without implants. TMA-gly:CPH (10:90 and 30:70) matrices produced mild inflammatory reactions by the end of 60 days, similar to those seen with PLAGA. TMA-gly: CPH (50: 50) produced moderate inflammatory reactions characterized by macrophages and edema. PMA-ala:CPH matrices elicited minimal inflammatory reactions that were characterized by fibrous encapsulation by the end of 60 days. In vivo degradation rates of poly(anhydride-co-imides) were similar to PLAGA. Both PMA-ala:CPH and TMA-gly: CPH matrices maintained their shapes and degraded at a constant rate over the period of two months. These polymers, possessing good mechanical properties and tissue compatibility, may be useful in weight-bearing applications in bone.

Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernandes, Claudia A.; Fievez, Laurence; Neyrinck, Audrey M.

Highlights: Black-Right-Pointing-Pointer Lipopolysaccharide-stimulated macrophages were treated with cambinol and sirtinol. Black-Right-Pointing-Pointer Cambinol and sirtinol decreased lipopolysaccharide-induced cytokines. Black-Right-Pointing-Pointer Cambinol decreased NF-{kappa}B activity but had no impact on p38 MAPK activation. Black-Right-Pointing-Pointer Sirtuins are an interesting target for the treatment of inflammatory diseases. -- Abstract: In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact ofmore » sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-{alpha}) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-{kappa}B) activity and inhibitor kappa B alpha (I{kappa}B{alpha}) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions.« less

Cold Condition Influence on the Pulmonary Function in Smoking Military Men

DTIC Science & Technology

2002-04-01

abundance, allergy and frequent airways acute inflammatory diseases in anamnesis and have been made routine clinical examination. 23-3 During...physical exercise, emotional stress etc.; and have in anamnesis (during last 2 year) 3-4 times and over acute airway inflammatory diseases: 17 persons

Pelvic Inflammatory Disease (PID)

MedlinePlus

... a serious condition, in women. 1 in 8 women with a history of PID experience difficulties getting pregnant. You can prevent PID if you know how to protect yourself. What is PID? Pelvic inflammatory disease is an infection of a woman’s reproductive organs. It is a complication often caused ...

Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation.

PubMed

Rayssiguier, Yves; Libako, Patrycja; Nowacki, Wojciech; Rock, Edmond

2010-06-01

Magnesium (Mg) intake is inadequate in the western diet and metabolic syndrome is highly prevalent in populations around the world. Epidemiological studies suggest that high Mg intake may reduce the risk but the possibility of confounding factors exists, given the strong association between Mg and other beneficial nutriments (vegetables, fibers, cereals). The concept that metabolic syndrome is an inflammatory condition may explain the role of Mg.Mg deficiency results in a stress effect and increased susceptibility to physiological damage produced by stress. Stress activates the hypothalamic-pituitary-adrenal axis (HPA) axis and the sympathetic nervous system. The activation of the renin-angiotensin-aldosterone system is a factor in the development of insulin resistance by increasing oxidative stress. In both humans and rats, aldosteronism results in an immunostimulatory state and leads to an inflammatory phenotype. Stress response induces the release of large quantities of excitatory amino acids and activates the nuclear factor NFkappaB, promoting translation of molecules involved in cell regulation, metabolism and apoptosis. The rise in neuropeptides is also well documented. Stress-induced HPA activation has been identified to play an important role in the preferential body fat accumulation but evidence that Mg is involved in body weight regulation is lacking. One of the earliest events in the acute response to stress is endothelial dysfunction. Endothelial cells actively contribute to inflammation by elaborating cytokines, synthesizing chemical mediators and expressing adhesion molecules. Experimental Mg deficiency in rats induces a clinical inflammatory syndrome characterized by leukocyte and macrophage activation, synthesis of inflammatory cytokines and acute phase proteins, extensive production of free radicals. An increase in extracellular Mg concentration decreases inflammatory effects, while reduction in extracellular Mg results in cell activation. The effect of Mg deficiency in the development of insulin resistance in the rat model is well documented. Inflammation occurring during experimental Mg deficiency is the mechanism that induces hypertriglyceridemia and pro-atherogenic changes in lipoprotein metabolism. The presence of endothelial dysfunction and dyslipidemia triggers platelet aggregability, thus increasing the risk of thrombotic events. Oxidative stress contributes to the elevation of blood pressure. The inflammatory syndrome induces activation of several factors, which are dependent on cytosolic Ca activation. Recent findings support the hypothesis that the Mg effect on intracellular Ca2+ homeostasis may be a common link between stress, inflammation and a possible relationship to metabolic syndrome.

Cytokine production in vitro and in rat model of colitis in response to Lactobacillus plantarum LS/07.

PubMed

Štofilová, Jana; Langerholc, Tomaž; Botta, Cristian; Treven, Primož; Gradišnik, Lidija; Salaj, Rastislav; Šoltésová, Alena; Bertková, Izabela; Hertelyová, Zdenka; Bomba, Alojz

2017-10-01

Over the past decade, it has become clear that specific probiotic lactobacilli are valuable in the prevention and treatment of infectious and inflammatory diseases of gastrointestinal tract but their successful application would benefit greatly from a better understanding of the mechanisms of individual strains. Hence, each probiotic strain should be characterized for their immune activity before being proposed for clinical applications. The aim of the study was to characterize the immunomodulatory activity of the strain Lactobacillus (L.) plantarum LS/07 in vitro using functional gut model and to study its anti-inflammatory potential in dextran sulphate sodium (DSS)-induced colitis in rats. We showed that L. plantarum LS/07 induced production of IL-10 in macrophages derived from blood monocytes as well as monocyte/macrophages cell line stimulated indirectly via enterocytes in vitro. In rat model of colitis, L. plantarum LS/07 attenuated the DSS-induced signs of inflammatory process in colon such as weight loss, diarrhoea, infiltration of inflammatory cells associated with decreased colon weight/length ratio, inhibited gut mucosa destruction and depletion of goblet cells. Moreover, the strain increased the concentration of anti-inflammatory cytokine IL-10 in mucosal tissue. In conclusion, the protective effects of L. plantarum LS/07 in the DSS-induced colitis model seem to be related to the stimulation of IL-10 and the restoration of goblet cells and indicate it as a good candidate to prevent and treat diseases associated with inflammation. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Vaccine against autoimmune disease: can helminths or their products provide a therapy?

PubMed

Zaccone, Paola; Cooke, Anne

2013-06-01

There is an increasing interest in exploiting the immunomodulatory effects of helminths and their products in treatment of diseases such as allergy, autoimmunity and inflammatory bowel disease. Detailed examination of the ways in which helminth derived products interact with the host immune system and with host physiology has revealed that these may be multifaceted and have almost certainly arisen following co-evolution of helminths and their hosts. Clinical trials have been initiated with encouraging results in the treatment of inflammatory bowel disease and also Multiple Sclerosis. Identification of key pathways that are manipulated by helminths to ameliorate ongoing inflammatory conditions increases the prospect of developing novel therapies for the treatment and possible prevention of a range of debilitating and life threatening conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Anti-inflammatory effect of the Salvia sclarea L. ethanolic extract on lipopolysaccharide-induced periodontitis in rats.

PubMed

Kostić, Milica; Kitić, Dušanka; Petrović, Milica B; Jevtović-Stoimenov, Tatjana; Jović, Marko; Petrović, Aleksandar; Živanović, Slavoljub

2017-03-06

Salvia sclarea L., clary, is an aromatic plant traditionally used in folk medicine for the treatment of various diseases and conditions. Although it has been primarily used as a stomachic, there are data on traditional use of S. sclarea as an agent against gingivitis, stomatitis and aphthae. The aim of the study was to examine the effect of the S. sclarea ethanolic extract on the lipopolysaccharide (LPS)-induced periodontitis in rats from the immunological and histopathological standpoint. Periodontal inflammation in rats was induced by repeated injections of LPS from Escherichia coli into the interdental papilla between the first and second right maxillary molars. The extract was administered two times a day by oral gavage (200mg/kg body weight). The inflammatory status was assessed by the measurements of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) of gingival tissues and descriptive analysis of histological sections of periodontium. Chemical characterization of the extract was determined using high performance liquid chromatography system (HPLC). Antioxidant activity of the extract was estimated with two in vitro complementary methods: 2,2-diphenyl-1-picrylhydrazyl and β-carotene/linoleic acid models. Treatment with S. sclarea extract, compared to the untreated group of the rats, significantly diminished the process of inflammation decreasing the levels of IL-1β, IL-6 and TNF-α, reducing the gingival tissue lesions and preserving bone alveolar resorption. Considerably smaller number of inflammatory cells and larger number of fibroblasts was noticed. The administration of the extract three days earlier did not have significant preventive effects. Rosmarinic acid was the predominant compound in the extract. The extract showed strong antioxidant effects in both test systems. S. sclarea extract manifested anti-inflammatory effect in LPS-induced periodontitis suggesting that it may have a role as a therapeutic agent in periodontal diseases. Having in mind that overproduction of reactive oxygen species is connected to periodontitis, the strong antioxidant capacity may be contributable to anti-inflammatory properties of the extract. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Monoethylhexyl Phthalate Elicits an Inflammatory Response in Adipocytes Characterized by Alterations in Lipid and Cytokine Pathways.

PubMed

Manteiga, Sara; Lee, Kyongbum

2017-04-01

A growing body of evidence links endocrine-disrupting chemicals (EDCs) with obesity-related metabolic diseases. While it has been shown that EDCs can predispose individuals toward adiposity by affecting developmental processes, little is known about the chemicals' effects on adult adipose tissue. Our aim was to study the effects of low, physiologically relevant doses of EDCs on differentiated murine adipocytes. We combined metabolomics, proteomics, and gene expression analysis to characterize the effects of mono-ethylhexyl phthalate (MEHP) in differentiated adipocytes. Repeated exposure to MEHP over several days led to changes in metabolite and enzyme levels indicating elevated lipogenesis and lipid oxidation. The chemical exposure also increased expression of major inflammatory cytokines, including chemotactic factors. Proteomic and gene expression analysis revealed significant alterations in pathways regulated by peroxisome proliferator activated receptor-γ (PPARγ). Inhibiting the nuclear receptor's activity using a chemical antagonist abrogated not only the alterations in PPARγ-regulated metabolic pathways, but also the increases in cytokine expression. Our results show that MEHP can induce a pro-inflammatory state in differentiated adipocytes. This effect is at least partially mediated PPARγ.

Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model

NASA Astrophysics Data System (ADS)

Wang, Xueding; Rajian, Justin; Shao, Xia; Chamberland, David L.; Girish, Gandikota

2014-03-01

Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.

Immunomodulatory effect of CD200-positive human placenta-derived stem cells in the early phase of stroke

PubMed Central

Kong, TaeHo; Park, Ji-Min; Jang, Ji Hyon; Kim, C-Yoon; Bae, Sang-Hun; Choi, Yuri; Jeong, Yun-Hwa; Kim, Chul; Chang, Sung Woon; Kim, Joopyung; Moon, Jisook

2018-01-01

Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs. The AMSCs transplanted into the ischemic rat model of stroke dramatically inhibited the expression of pro-inflammatory cytokines and up-regulated CD200, as compared with the levels in the sham-treated group. Moreover, decreased microglia activation in the boundary region and improvements in behavior were confirmed in AMSC-treated ischemic rats. The results suggested that the highly expressed CD200 from the AMSCs in a hypoxic environment modulates levels of inflammatory cytokines and microglial activation, thus increasing the therapeutic recovery potential after hypoxic-ischemic brain injury, and further demonstrated the immunomodulatory function of AMSCs in a stroke model. PMID:29328072

Effects of a Cognitive Behavioral Therapy Intervention Trial to Improve Disease Outcomes in Children with Inflammatory Bowel Disease.

PubMed

Levy, Rona L; van Tilburg, Miranda A L; Langer, Shelby L; Romano, Joan M; Walker, Lynn S; Mancl, Lloyd A; Murphy, Tasha B; Claar, Robyn L; Feld, Shara I; Christie, Dennis L; Abdullah, Bisher; DuPen, Melissa M; Swanson, Kimberly S; Baker, Melissa D; Stoner, Susan A; Whitehead, William E

2016-09-01

Studies testing the efficacy of behavioral interventions to modify psychosocial sequelae of inflammatory bowel disease in children are limited. This report presents outcomes through a 6-month follow-up from a large randomized controlled trial testing the efficacy of a cognitive behavioral intervention for children with inflammatory bowel disease and their parents. One hundred eighty-five children aged 8 to 17 years with a diagnosis of Crohn's disease or ulcerative colitis and their parents were randomized to one of two 3-session conditions: (1) a social learning and cognitive behavioral therapy condition or (2) an education support condition designed to control for time and attention. There was a significant overall treatment effect for school absences due to Crohn's disease or ulcerative colitis (P < 0.05) at 6 months after treatment. There was also a significant overall effect after treatment for child-reported quality of life (P < 0.05), parent-reported increases in adaptive child coping (P < 0.001), and reductions in parents' maladaptive responses to children's symptoms (P < 0.05). Finally, exploratory analyses indicated that for children with a higher level of flares (2 or more) prebaseline, those in social learning and cognitive behavioral therapy condition experienced a greater reduction in flares after treatment. This trial suggests that a brief cognitive behavioral intervention for children with inflammatory bowel disease and their parents can result in improved child functioning and quality of life, and for some children may decrease disease activity.

Deacylation of Purified Lipopolysaccharides by Cellular and Extracellular Components of a Sterile Rabbit Peritoneal Inflammatory Exudate

PubMed Central

Weinrauch, Yvette; Katz, Seth S.; Munford, Robert S.; Elsbach, Peter; Weiss, Jerrold

1999-01-01

The extent to which the mammalian host is capable of enzymatic degradation and detoxification of bacterial lipopolysaccharides (LPS) is still unknown. Partial deacylation of LPS by the enzyme acyloxyacyl hydrolase (AOAH) provides such a mechanism, but its participation in the disposal of LPS under physiological conditions has not been established. In this study, deacylation of isolated radiolabeled LPS by both cellular and extracellular components of a sterile inflammatory peritoneal exudate elicited in rabbits was examined ex vivo. AOAH-like activity, tested under artificial conditions (pH 5.4, 0.1% Triton X-100), was evident in all components of the exudate (mononuclear cells [MNC] > polymorphonuclear leukocytes [PMN] > inflammatory [ascitic] fluid [AF]). Under more physiological conditions, in a defined medium containing purified LPS-binding protein, the LPS-deacylating activity of MNC greatly exceeded that of PMN. In AF, MNC (but not PMN) also produced rapid and extensive CD14-dependent LPS deacylation. Under these conditions, almost all MNC-associated LPS underwent deacylation within 1 h, a rate greatly exceeding that previously found in any cell type. The remaining extracellular LPS was more slowly subject to CD14-independent deacylation in AF. Quantitative analysis showed a comparable release of laurate and myristate but no release of 3-hydroxymyristate, consistent with an AOAH-like activity. These findings suggest a major role for CD14+ MNC and a secondary role for AF in the deacylation of cell-free LPS at extravascular inflammatory sites. PMID:10377115

Prevalence of foot problems in people with inflammatory arthritis in Singapore.

PubMed

Carter, K; Lahiri, M; Cheung, P P; Santosa, A; Rome, K

2016-01-01

Foot problems are highly prevalent in people with inflammatory arthritis reported from studies in the UK, Europe and New Zealand, but there is limited evidence from Southeast Asia. The study aim was to evaluate the prevalence of foot problems in people with inflammatory arthritis in Singapore. People with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a tertiary hospital in Singapore. Disease and clinical characteristics included age, sex, disease duration, current blood tests and medications. The Leeds Foot Impact Scale was used to evaluate foot impairment/disability and the Modified Health Assessment Questionnaire was used to assess global function. We recruited 101 people with inflammatory arthritis, of which 50 % were female. The majority of participants were Chinese (70 %). The mean (SD) age was 52 (15) years, and the mean (SD) disease duration was 9.3 (0.3) years. The most commonly reported inflammatory arthritic conditions were rheumatoid arthritis (46), gout (31) and spondyloarthritis (15 %). The mean (SD) of the total Leeds Foot Impact Scale was 17 (13) indicating moderate to severe levels of foot impairment and activity limitation. Over 80 of participants reported foot pain during the course of their condition, and 48 % reported current foot pain. Despite the high prevalence of foot pain, only 21 participants (21 %) had been referred to a podiatrist. This is the first study to investigate the prevalence of foot problems in people with inflammatory arthritis from Singapore. The majority of the participants reported foot problems, but had not been referred to a podiatry service.

Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases.

PubMed

Coudriet, Gina M; He, Jing; Trucco, Massimo; Mars, Wendy M; Piganelli, Jon D

2010-11-02

The generation of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β fuel the acute phase response (APR). To maintain body homeostasis, the increase of inflammatory proteins is resolved by acute phase proteins via presently unknown mechanisms. Hepatocyte growth factor (HGF) is transcribed in response to IL-6. Since IL-6 production promotes the generation of HGF and induces the APR, we posited that accumulating HGF might be a likely candidate for quelling excess inflammation under non-pathological conditions. We sought to assess the role of HGF and how it influences the regulation of inflammation utilizing a well-defined model of inflammatory activation, lipopolysaccharide (LPS)-stimulation of bone marrow derived macrophages (BMM). BMM were isolated from C57BL6 mice and were stimulated with LPS in the presence or absence of HGF. When HGF was present, there was a decrease in production of the pro-inflammatory cytokine IL-6, along with an increase in the anti-inflammatory cytokine IL-10. Altered cytokine production correlated with an increase in phosphorylated GSK3β, increased retention of the phosphorylated NFκB p65 subunit in the cytoplasm, and an enhanced interaction between CBP and phospho-CREB. These changes were a direct result of signaling through the HGF receptor, MET, as effects were reversed in the presence of a selective inhibitor of MET (SU11274) or when using BMM from macrophage-specific conditional MET knockout mice. Combined, these data provide compelling evidence that under normal circumstances, HGF acts to suppress the inflammatory response.

Non-infectious inflammatory genital lesions.

PubMed

Andreassi, Lucio; Bilenchi, Roberta

2014-01-01

The genitalia may be the site of non-infectious inflammatory lesions that are generally manifested as balanoposthitis and vulvovaginitis. In men, these forms constitute 50% of all balanoposthitis forms, and in women, vulvovaginitis frequency is even higher. They consist of genital locations of general skin diseases, such as psoriasis, lichen planus, lichen sclerosus, and other clinical entities with their own physiognomy, such as Zoon's balanitis-vulvitis. Diagnosis of genital non-infectious inflammatory lesions is usually made on clinical criteria. A biopsy is only necessary for the identification of clinical conditions that may simulate inflammatory form but are actually premalignant processes. © 2014 Elsevier Inc. All rights reserved.

Predictors of Aggressive Inflammatory Bowel Disease

PubMed Central

Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.

2011-01-01

Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958

Release of cystic fibrosis airway inflammatory markers from Pseudomonas aeruginosa-stimulated human neutrophils involves NADPH oxidase-dependent extracellular DNA trap formation.

PubMed

Yoo, Dae-goon; Winn, Matthew; Pang, Lan; Moskowitz, Samuel M; Malech, Harry L; Leto, Thomas L; Rada, Balázs

2014-05-15

Cystic fibrosis (CF) airways are characterized by bacterial infections, excess mucus production, and robust neutrophil recruitment. The main CF airway pathogen is Pseudomonas aeruginosa. Neutrophils are not capable of clearing the infection. Neutrophil primary granule components, myeloperoxidase (MPO) and human neutrophil elastase (HNE), are inflammatory markers in CF airways, and their increased levels are associated with poor lung function. Identifying the mechanism of MPO and HNE release from neutrophils is of high clinical relevance for CF. In this article, we show that human neutrophils release large amounts of neutrophil extracellular traps (NETs) in the presence of P. aeruginosa. Bacteria are entangled in NETs and colocalize with extracellular DNA. MPO, HNE, and citrullinated histone H4 are all associated with DNA in Pseudomonas-triggered NETs. Both laboratory standard strains and CF isolates of P. aeruginosa induce DNA, MPO, and HNE release from human neutrophils. The increase in peroxidase activity of neutrophil supernatants after Pseudomonas exposure indicates that enzymatically active MPO is released. P. aeruginosa induces a robust respiratory burst in neutrophils that is required for extracellular DNA release. Inhibition of the cytoskeleton prevents Pseudomonas-initiated superoxide production and DNA release. NADPH oxidase inhibition suppresses Pseudomonas-induced release of active MPO and HNE. Blocking MEK/ERK signaling results in only minimal inhibition of DNA release induced by Pseudomonas. Our data describe in vitro details of DNA, MPO, and HNE release from neutrophils activated by P. aeruginosa. We propose that Pseudomonas-induced NET formation is an important mechanism contributing to inflammatory conditions characteristic of CF airways.

Effects of the antirheumatic remedy hox alpha--a new stinging nettle leaf extract--on matrix metalloproteinases in human chondrocytes in vitro.

PubMed

Schulze-Tanzil, G; de, Souza P; Behnke, B; Klingelhoefer, S; Scheid, A; Shakibaei, M

2002-04-01

Inflammatory joint diseases are characterized by enhanced extracellular matrix degradation which is predominantly mediated by cytokine-stimulated upregulation of matrix metalloproteinase (MMP) expression. Besides tumour necrosis factor-alpha (TNF-alpha), Interleukin-1beta (IL-1beta) produced by articular chondrocytes and synovial macrophages, is the most important cytokine stimulating MMP expression under inflammatory conditions. Blockade of these two cytokines and their downstream effectors are suitable molecular targets of antirheumatic therapy. Hox alpha is a novel stinging nettle (Urtica dioica/Urtica urens) leaf extract used for treatment of rheumatic diseases. The aim of the present study was to clarify the effects of Hox alpha and the monosubstance 13-HOTrE (13-Hydroxyoctadecatrienic acid) on the expression of matrix metalloproteinase-1, -3 and -9 proteins (MMP-1, -3, -9). Human chondrocytes were cultured on collagen type-II-coated petri dishes, exposed to IL-1beta and treated with or without Hox alpha and 13-HOTrE. A close analysis by immunofluorescence microscopy and western blot analysis showed that Hox alpha and 13-HOTrE significantly suppressed IL-1beta-induced expression of matrix metalloproteinase-1, -3 and -9 proteins on the chondrocytes in vitro. The potential of Hox alpha and 13-HOTrE to suppress the expression of matrix metalloproteinases may explain the clinical efficacy of stinging nettle leaf extracts in treatment of rheumatoid arthritis. These results suggest that the monosubstance 13-HOTrE is one of the more active antiinflammatory substances in Hox alpha and that Hox alpha may be a promising remedy for therapy of inflammatory joint diseases.

Role of Nonneuronal TRPV4 Signaling in Inflammatory Processes.

PubMed

Rajasekhar, Pradeep; Poole, Daniel P; Veldhuis, Nicholas A

2017-01-01

Transient receptor potential (TRP) ion channels are important signaling components in nociceptive and inflammatory pathways. This is attributed to their ability to function as polymodal sensors of environmental stimuli (chemical and mechanical) and as effector molecules in receptor signaling pathways. TRP vanilloid 4 (TRPV4) is a nonselective cation channel that is activated by multiple endogenous stimuli including shear stress, membrane stretch, and arachidonic acid metabolites. TRPV4 contributes to many important physiological processes and dysregulation of its activity is associated with chronic conditions of metabolism, inflammation, peripheral neuropathies, musculoskeletal development, and cardiovascular regulation. Mechanosensory and receptor- or lipid-mediated signaling functions of TRPV4 have historically been attributed to central and peripheral neurons. However, with the development of potent and selective pharmacological tools, transgenic mice and improved molecular and imaging techniques, many new roles for TRPV4 have been revealed in nonneuronal cells. In this chapter, we discuss these recent findings and highlight the need for greater characterization of TRPV4-mediated signaling in nonneuronal cell types that are either directly associated with neurons or indirectly control their excitability through release of sensitizing cellular factors. We address the integral role of these cells in sensory and inflammatory processes as well as their importance when considering undesirable on-target effects that may be caused by systemic delivery of TRPV4-selective pharmaceutical agents for treatment of chronic diseases. In future, this will drive a need for targeted drug delivery strategies to regulate such a diverse and promiscuous protein. © 2017 Elsevier Inc. All rights reserved.

Splanchnic-aortic inflammatory axis in experimental portal hypertension

PubMed Central

Aller, Maria-Angeles; de las Heras, Natalia; Nava, Maria-Paz; Regadera, Javier; Arias, Jaime; Lahera, Vicente

2013-01-01

Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension. PMID:24307792

Correlation between clinical and histopathological diagnoses in periapical inflammatory lesions.

PubMed

Diegues, Liliane Lopes; Colombo Robazza, Carlos Roberto; Costa Hanemann, João Adolfo; Costa Pereira, Alessandro Antônio; Silva, Cléverson O

2011-08-01

  The purpose of the present study was to evaluate the correlation between clinical and histopathological diagnoses of periapical inflammatory lesions, focusing mainly on cystic conditions.   Files dating from 1998 to 2006 at the Oral Pathology Laboratory, School of Dentistry, Alfenas Federal University, Brazil, were reviewed to identify cases with histopathological diagnoses of periapical inflammatory lesions. A total of 1788 files were analyzed, and 255 cases were identified with clinical diagnoses of periapical inflammatory lesions.   The most prevalent clinical diagnosis was apical periodontal cyst (59%), followed by periapical granuloma (20%), and dentoalveolar abscess (2%). After histopathological analysis, 53% of the cases represented apical periodontal cyst, 42% periapical granuloma, and 5% dentoalveolar abscess.   The outcomes of the present study show a high prevalence of periapical cysts among periapical inflammatory lesions. Moreover, this study highlights the importance of histopathological evaluation for the correct diagnosis of periapical inflammatory lesions. © 2011 Blackwell Publishing Asia Pty Ltd.