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Sample records for inflammation resembling inflammatory

  1. Inflammatory Monocytes Recruited to the Liver within 24 Hours after Virus-Induced Inflammation Resemble Kupffer Cells but Are Functionally Distinct

    PubMed Central

    Movita, Dowty; Biesta, Paula; Kreefft, Kim; Haagmans, Bart; Zuniga, Elina; Herschke, Florence; De Jonghe, Sandra; Janssen, Harry L. A.; Gama, Lucio; Boonstra, Andre

    2015-01-01

    ABSTRACT Due to a scarcity of immunocompetent animal models for viral hepatitis, little is known about the early innate immune responses in the liver. In various hepatotoxic models, both pro- and anti-inflammatory activities of recruited monocytes have been described. In this study, we compared the effect of liver inflammation induced by the Toll-like receptor 4 ligand lipopolysaccharide (LPS) with that of a persistent virus, lymphocytic choriomeningitis virus (LCMV) clone 13, on early innate intrahepatic immune responses in mice. LCMV infection induces a remarkable influx of inflammatory monocytes in the liver within 24 h, accompanied by increased transcript levels of several proinflammatory cytokines and chemokines in whole liver. Importantly, while a single LPS injection results in similar recruitment of inflammatory monocytes to the liver, the functional properties of the infiltrating cells are dramatically different in response to LPS versus LCMV infection. In fact, intrahepatic inflammatory monocytes are skewed toward a secretory phenotype with impaired phagocytosis in LCMV-induced liver inflammation but exhibit increased endocytic capacity after LPS challenge. In contrast, F4/80high-Kupffer cells retain their steady-state endocytic functions upon LCMV infection. Strikingly, the gene expression levels of inflammatory monocytes dramatically change upon LCMV exposure and resemble those of Kupffer cells. Since inflammatory monocytes outnumber Kupffer cells 24 h after LCMV infection, it is highly likely that inflammatory monocytes contribute to the intrahepatic inflammatory response during the early phase of infection. Our findings are instrumental in understanding the early immunological events during virus-induced liver disease and point toward inflammatory monocytes as potential target cells for future treatment options in viral hepatitis. IMPORTANCE Insights into how the immune system deals with hepatitis B virus (HBV) and HCV are scarce due to the lack of

  2. Synthesized enone fatty acids resembling metabolites from gut microbiota suppress macrophage-mediated inflammation in adipocytes.

    PubMed

    Yang, Ha-Eun; Li, Yongjia; Nishimura, Akira; Jheng, Huei-Fen; Yuliana, Ana; Kitano-Ohue, Ryuji; Nomura, Wataru; Takahashi, Nobuyuki; Kim, Chu-Sook; Yu, Rina; Kitamura, Nahoko; Park, Si-Bum; Kishino, Shigenobu; Ogawa, Jun; Kawada, Teruo; Goto, Tsuyoshi

    2017-10-01

    Recent reports indicate that gut microbiota and their metabolites may regulate host inflammatory conditions, including the chronic inflammation of obese adipose tissues. In this study, we investigated whether specific synthesized fatty acids, identical to the metabolites generated by gut microbiota, act as anti-inflammatory factors in obesity-induced inflammation. We first used lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages to examine the anti-inflammatory effect of fatty acids synthesized to resemble representative polyunsaturated fatty acid metabolites from gut microbiota. Fatty acids containing an enone structure showed the most potent anti-inflammatory activity. Enone fatty acids also displayed anti-inflammatory effects on macrophages cocultured with hypertrophied 3T3-L1 or immortalized primary adipocytes; and macrophages stimulated with 3T3-L1 adipocyte conditioned medium. Consistently, the beneficial outcome was revealed in the case of LPS- and obesity-induced inflammatory cytokine stimulation in ex vivo adipose tissues. Furthermore, these fatty acids recovered the suppression of β-adrenergic receptor-stimulated uncoupling protein 1 expression and secretion of adiponectin in C3H10T1/2 and 3T3-L1 adipocytes, respectively, under inflammatory conditions, suggesting that enone fatty acids can ameliorate dysfunctions of adipocytes induced by inflammation. These findings indicate that synthesized enone fatty acids show potent anti-inflammatory effects, leading to the improvement of inflammation-induced dysfunctions in adipocytes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Feline epidermal nevi resembling human inflammatory linear verrucous epidermal nevus.

    PubMed

    Sato, Masafumi; Kariya, Kazuhiro; Matsumoto, Munetaka; Itoh, Miyuki; Kobayashi, Yoshiyasu; Nishifuji, Koji; Kamiie, Junichi; Shirota, Kinji

    2012-10-01

    Multiple, pigmented, verrucous, cutaneous lesions in a 2-year-old female cat were pathologically examined. The lesions were linearly arranged on the right side of the body, and had developed along with moderate pruritus since infancy. Histologically, prominent exophytic, papillomatous outgrowths of the epidermis and acanthosis with intense ortho and parakeratotic hyperkeratosis were characteristic of the lesions. Dermal inflammation with mononuclear cells, neutrophils, and eosinophils was also noted. Inclusion bodies, cellular degeneration, and intranuclear viral particles suggesting papillomavirus infection in the keratinocytes were not observed. Papillomavirus antigen and DNA were not detected in the lesions by immunohistochemistry and polymerase chain reaction, respectively. In accordance with these clinical and histopathological features, the cutaneous lesions of the present cat were diagnosed as epidermal nevi, which were consistent with human inflammatory linear verrucous epidermal nevi.

  4. Aberrant Mucin Assembly in Mice Causes Endoplasmic Reticulum Stress and Spontaneous Inflammation Resembling Ulcerative Colitis

    PubMed Central

    Price, Gareth R; Tauro, Sharyn B; Taupin, Douglas; Thornton, David J; Png, Chin Wen; Crockford, Tanya L; Cornall, Richard J; Adams, Rachel; Kato, Masato; Nelms, Keats A; Hong, Nancy A; Florin, Timothy H. J; Goodnow, Christopher C; McGuckin, Michael A

    2008-01-01

    Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterised the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis. Methods and Findings By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p < 0.01) and chronic diarrhoea. Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1β, TNF-α, and IFN-γ was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-γ, TNF-α, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar

  5. Extracutaneous neutrophilic inflammation in a dog with lesions resembling Sweet's Syndrome.

    PubMed

    Johnson, Charles S; May, Elizabeth R; Myers, Ronald K; Hostetter, Jesse M

    2009-06-01

    A 7-year-old-spayed female standard poodle dog presented to the Iowa State University Veterinary Teaching Hospital with an 8-day history of lethargy, left hind limb lameness, ptyalism and peripheral lymphadenomegaly. On physical examination, the dog was lethargic, febrile (40.5 degrees C) and had multifocal to coalescing erythematous papular to pustular eruptions on the skin of all four limbs, periocularly and on the ventral and lateral thorax and abdomen. Histopathological findings from skin biopsies of the papules revealed a severe diffuse neutrophilic dermatitis with sub- and intra-epithelial pustules. Four days after being admitted the dog died from cardiac and respiratory failure. At necropsy, in addition to the multifocal to coalescing erythematous papules, the skin contained scattered pustules. Additionally, the subcutaneous tissue surrounding the right stifle was diffusely oedematous, and the peripheral and visceral lymph nodes were enlarged. The predominant histologic lesion was neutrophilic inflammation, in the absence of detectable bacteria in the skin, heart, lungs, oesophagus and left tarsus. In the absence of neoplasia or bacteraemia, a syndrome similar to Sweet's Syndrome should be considered as a differential diagnosis in dogs with cutaneous and extracutaneous neutrophilic infiltrates.

  6. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  7. Oral Inflammatory Diseases and Systemic Inflammation: Role of the Macrophage

    PubMed Central

    Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.

    2012-01-01

    Inflammation is a complex reaction to injurious agents and includes vascular responses, migration, and activation of leukocytes. Inflammation starts with an acute reaction, which evolves into a chronic phase if allowed to persist unresolved. Acute inflammation is a rapid process characterized by fluid exudation and emigration of leukocytes, primarily neutrophils, whereas chronic inflammation extends over a longer time and is associated with lymphocyte and macrophage infiltration, blood vessel proliferation, and fibrosis. Inflammation is terminated when the invader is eliminated, and the secreted mediators are removed; however, many factors modify the course and morphologic appearance as well as the termination pattern and duration of inflammation. Chronic inflammatory illnesses such as diabetes, arthritis, and heart disease are now seen as problems that might have an impact on the periodontium. Reciprocal effects of periodontal diseases are potential factors modifying severity in the progression of systemic inflammatory diseases. Macrophages are key cells for the inflammatory processes as regulators directing inflammation to chronic pathological changes or resolution with no damage or scar tissue formation. As such, macrophages are involved in a remarkably diverse array of homeostatic processes of vital importance to the host. In addition to their critical role in immunity, macrophages are also widely recognized as ubiquitous mediators of cellular turnover and maintenance of extracellular matrix homeostasis. In this review, our objective is to identify macrophage-mediated events central to the inflammatory basis of chronic diseases, with an emphasis on how control of macrophage function can be used to prevent or treat harmful outcomes linked to uncontrolled inflammation. PMID:22623923

  8. Guinea-pig interpubic joint (symphysis pubica) relaxation at parturition: Underlying cellular processes that resemble an inflammatory response

    PubMed Central

    Rodríguez, Horacio A; Ortega, Hugo H; Ramos, Jorge G; Muñoz-de-Toro, Mónica; Luque, Enrique H

    2003-01-01

    Background At term, cervical ripening in coordination with uterine contractions becomes a prerequisite for a normal vaginal delivery. Currently, cervical ripening is considered to occur independently from uterine contractions. Many evidences suggest that cervical ripening resembles an inflammatory process. Comparatively little attention has been paid to the increased flexibility of the pelvic symphysis that occurs in many species to enable safe delivery. The aim of this study was to investigate whether the guinea-pig interpubic joint relaxation process observed during late pregnancy and parturition resembles an inflammatory process. Methods Samples of pubic symphysis were taken from pregnant guinea-pigs sacrificed along gestation, parturition and postpartum. Serial sections of paraffin-embedded tissues were used to measure the interpubic distance on digitalized images, stained with Giemsa to quantify leukocyte infiltration and to describe the vascular area changes, or studied by the picrosirius-polarization method to evaluate collagen remodeling. P4 and E2 serum levels were measured by a sequential immunometric assay. Results Data showed that the pubic relaxation is associated with an increase in collagen remodeling. In addition, a positive correlation between E2 serum levels and the increase in the interpubic distance was found. On the other hand, a leukocyte infiltration in the interpubic tissue around parturition was described, with the presence of almost all inflammatory cells types. At the same time, histological images show an increase in vascular area (angiogenesis). Eosinophils reached their highest level immediately before parturition; whereas for the neutrophilic and mononuclear infiltration higher values were recorded one day after parturition. Correlation analysis showed that eosinophils and mononuclear cells were positively correlated with E2 levels, but only eosinophilic infiltration was associated with collagen remodeling. Additionally, we observed

  9. Role of inflammation and inflammatory mediators in colorectal cancer.

    PubMed

    Dubois, Raymond N

    2014-01-01

    Chronic inflammation is a risk factor for several different cancers including colorectal cancer (CRC). However, the mechanisms underlying the contribution of inflammation to cancer remain elusive. Pro-inflammatory mediators such as cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer progression. Here, we show that COX-2 is an immediate-early response gene induced by growth factors and pro-inflammatory cytokines and its levels are elevated in human CRCs. Furthermore, we show that COX-2-derived PGE2 promotes colonic tumor growth via silencing certain tumor suppressors and DNA repair genes by DNA methylation in colonic epithelial tumor cells. We also report that C-X-C motif chemokine receptor 2 accelerates colonic inflammation and colitis-associated tumorigenesis by mediating myeloid-derived suppressor cell recruitment to the tumor microenvironment. These findings not only support a rationale to target these pro-inflammatory pathways for cancer prevention and treatment but also provide support for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression.

  10. Role of Inflammation and Inflammatory Mediators in Colorectal Cancer

    PubMed Central

    Dubois, Raymond N.

    2014-01-01

    Chronic inflammation is a risk factor for several different cancers including colorectal cancer (CRC). However, the mechanisms underlying the contribution of inflammation to cancer remain elusive. Pro-inflammatory mediators such as cyclooxygenase 2 (COX-2) and prostaglandin E2 (PGE2) contribute to cancer progression. Here, we show that COX-2 is an immediate-early response gene induced by growth factors and pro-inflammatory cytokines and its levels are elevated in human CRCs. Furthermore, we show that COX-2−derived PGE2 promotes colonic tumor growth via silencing certain tumor suppressors and DNA repair genes by DNA methylation in colonic epithelial tumor cells. We also report that C-X-C motif chemokine receptor 2 accelerates colonic inflammation and colitis-associated tumorigenesis by mediating myeloid-derived suppressor cell recruitment to the tumor microenvironment. These findings not only support a rationale to target these pro-inflammatory pathways for cancer prevention and treatment but also provide support for developing new therapeutic approaches to subvert chronic inflammation- and tumor-induced immunosuppression. PMID:25125751

  11. The role of inflammation in inflammatory breast cancer.

    PubMed

    Fouad, Tamer M; Kogawa, Takahiro; Reuben, James M; Ueno, Naoto T

    2014-01-01

    Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Despite extensive study, whether inflammation contributes to the tumorigenicity or aggressiveness of IBC remains largely unknown. In this chapter, we will review the potential role played by inflammation in IBC based on the results of in vitro, in vivo, and patient studies. Current evidence suggests that several major inflammatory signaling pathways are constitutively active in IBC and breast cancer. Among them, the NF-κB, COX-2, and JAK/STAT signaling systems seem to play a major role in the tumorigenesis of IBC. Inflammatory molecules such as interleukin-6, tumor necrosis factor alpha (TNF-α), and gamma interferon have been shown to contribute to malignant transformation in preclinical studies of IBC, while transforming growth factor-β, interleukins 8 and 1β, as well as TNF-α appear to play a role in proliferation, survival, epithelial-mesenchymal transition, invasion, and metastasis. In this chapter, we also describe work thus far involving inhibitors of inflammation in the development of prevention and treatment strategies for IBC.

  12. The inflammation highway: metabolism accelerates inflammatory traffic in obesity.

    PubMed

    Johnson, Amy R; Milner, J Justin; Makowski, Liza

    2012-09-01

    As humans evolved, perhaps the two strongest selection determinants of survival were a robust immune response able to clear bacterial, viral, and parasitic infection and an ability to efficiently store nutrients to survive times when food sources were scarce. These traits are not mutually exclusive. It is now apparent that critical proteins necessary for regulating energy metabolism, such as peroxisome proliferator-activated receptors, Toll-like receptors, and fatty acid-binding proteins, also act as links between nutrient metabolism and inflammatory pathway activation in immune cells. Obesity in humans is a symptom of energy imbalance: the scale has been tipped such that energy intake exceeds energy output and may be a result, in part, of evolutionary selection toward a phenotype characterized by efficient energy storage. As discussed in this review, obesity is a state of low-grade, chronic inflammation that promotes the development of insulin resistance and diabetes. Ironically, the formation of systemic and/or local, tissue-specific insulin resistance upon inflammatory cell activation may actually be a protective mechanism that co-evolved to repartition energy sources within the body during times of stress during infection. However, the point has been reached where a once beneficial adaptive trait has become detrimental to the health of the individual and an immense public health and economic burden. This article reviews the complex relationship between obesity, insulin resistance/diabetes, and inflammation, and although the liver, brain, pancreas, muscle, and other tissues are relevant, we focus specifically on how the obese adipose microenvironment can promote immune cell influx and sustain damaging inflammation that can lead to the onset of insulin resistance and diabetes. Finally, we address how substrate metabolism may regulate the immune response and discuss how fuel uptake and metabolism may be a targetable approach to limit or abrogate obesity

  13. The inflammation highway: metabolism accelerates inflammatory traffic in obesity

    PubMed Central

    Johnson, Amy R.; Milner, J. Justin; Makowski, Liza

    2012-01-01

    Summary As humans evolved, perhaps the two strongest selection determinants of survival were a robust immune response able to clear bacterial, viral, and parasitic infection and an ability to efficiently store nutrients to survive times when food sources were scarce. These traits are not mutually exclusive. It is now apparent that critical proteins necessary for regulating energy metabolism such as peroxisome proliferator-activated receptors (PPARs), Toll-like receptors (TLRs), and fatty acid-binding proteins (FABPs) also act as links between nutrient metabolism and inflammatory pathway activation in immune cells. Obesity in humans is a symptom of energy imbalance: the scale has been tipped such that energy intake exceeds energy output and may be a result, in part, of evolutionary selection toward a phenotype characterized by efficient energy storage. As discussed in this review, obesity is a state of low-grade, chronic inflammation that promotes the development of insulin resistance and diabetes. Ironically, the formation of systemic and/or local, tissue-specific insulin resistance upon inflammatory cell activation may actually be a protective mechanism that co-evolved to repartition energy sources within the body during times of stress during infection. However, the point has been reached where a once beneficial adaptive trait has become detrimental to the health of the individual and an immense public health and economic burden. This article reviews the complex relationship between obesity, insulin resistance/diabetes, and inflammation, and while the liver, brain, pancreas, muscle, and other tissues are relevant, we focus specifically on how the obese adipose microenvironment can promote immune cell influx and sustain damaging inflammation that can lead to the onset of insulin resistance and diabetes. Finally, we address how substrate metabolism may regulate the immune response and discuss how fuel uptake and metabolism may be a targetable approach to limit or

  14. Relationship between methylation and colonic inflammation in inflammatory bowel disease

    PubMed Central

    Lobatón, Triana; Azuara, Daniel; Rodríguez-Moranta, Francisco; Loayza, Carolina; Sanjuan, Xavier; de Oca, Javier; Fernández-Robles, Ana; Guardiola, Jordi; Capellá, Gabriel

    2014-01-01

    AIM: To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients. METHODS: We evaluated the methylation status of 2 genes (SLIT2 and TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative colitis and 9 Crohn’s colitis) using methylation-specific melting curve analysis. The relationships between methylation status and clinical, biological, endoscopic and histological activities were evaluated. Twenty-three of the 38 patients had a second colonoscopy and were included in a longitudinal analysis. Numerical results were given as the means ± SD of the sample and range, except when specified. Student t analysis, U Mann Whitney and ANOVA factor were used to compare the means. Qualitative results were based on the χ2 test. RESULTS: SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher in samples with acute inflammation (56.5%) than in samples with chronic (24%) or absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was only significant with endoscopic activity. Methylation was higher in the distal colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the multivariate analysis, only inflammation status (and not disease duration or extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI: 1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of endoscopic remission was protective for methylation. CONCLUSION: Endoscopic and histological inflammation are predictive for SLIT2 methylation. PMID:25132780

  15. Relationship between methylation and colonic inflammation in inflammatory bowel disease.

    PubMed

    Lobatón, Triana; Azuara, Daniel; Rodríguez-Moranta, Francisco; Loayza, Carolina; Sanjuan, Xavier; de Oca, Javier; Fernández-Robles, Ana; Guardiola, Jordi; Capellá, Gabriel

    2014-08-14

    To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients. We evaluated the methylation status of 2 genes (SLIT2 and TGFB2) in 226 biopsies taken from 62 colonoscopies of 38 patients (29 ulcerative colitis and 9 Crohn's colitis) using methylation-specific melting curve analysis. The relationships between methylation status and clinical, biological, endoscopic and histological activities were evaluated. Twenty-three of the 38 patients had a second colonoscopy and were included in a longitudinal analysis. Numerical results were given as the means ± SD of the sample and range, except when specified. Student t analysis, U Mann Whitney and ANOVA factor were used to compare the means. Qualitative results were based on the χ(2) test. SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission (55% vs 18%, P < 0.001). SLIT2 methylation was also higher in samples with acute inflammation (56.5%) than in samples with chronic (24%) or absent inflammation (15%) (P < 0.001). For TGFB2 methylation, the correlation was only significant with endoscopic activity. Methylation was higher in the distal colon for both genes (P < 0.001 for SLIT2 and P = 0.022 for TGFB2). In the multivariate analysis, only inflammation status (and not disease duration or extension) was independently associated with SLIT2 methylation [OR = 6.6 (95%CI: 1.65-27.36), P = 0.009]. In the longitudinal analysis, the maintenance of endoscopic remission was protective for methylation. Endoscopic and histological inflammation are predictive for SLIT2 methylation.

  16. Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

    PubMed Central

    Adán, Norma; Guzmán-Morales, Jessica; Ledesma-Colunga, Maria G.; Perales-Canales, Sonia I.; Quintanar-Stéphano, Andrés; López-Barrera, Fernando; Méndez, Isabel; Moreno-Carranza, Bibiana; Triebel, Jakob; Binart, Nadine; Martínez de la Escalera, Gonzalo; Thebault, Stéphanie; Clapp, Carmen

    2013-01-01

    Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3–dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor–null (Prlr–/–) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA. PMID:23908112

  17. Mapping inflammation onto mood: Inflammatory mediators of anhedonia.

    PubMed

    Swardfager, Walter; Rosenblat, Joshua D; Benlamri, Meriem; McIntyre, Roger S

    2016-05-01

    Evidence supports inflammatory involvement in mood and cognitive symptoms across psychiatric, neurological and medical disorders; however, inflammation is not a sensitive or specific characteristic of these diagnoses. The National Institute of Mental Health Research Domain Criteria (RDoC) ask for a shift away from symptom-based diagnoses toward a transdiagnostic neurobiological focus in the study of brain illnesses. The RDoC matrix may provide a useful framework for integrating the effects of inflammation on brain function. Based on preclinical and clinical findings, relevant relationships span negative and positive valence systems, cognitive systems, systems for social processes and arousal/regulatory systems. As an exemplar, we consider the psychopathological domain of anhedonia, conceptualizing the relevance of inflammation (e.g., cellular immunity) and downstream processes (e.g., indoleamine 2,3-dioxygenase activation and oxidative inactivation of tetrahydrobiopterin) across RDoC units of analysis (e.g., catecholamine neurotransmitter molecules, nucleus accumbens medium spiny neuronal cells, dopaminergic mesolimbic and mesocortical reward circuits, animal paradigms, etc.). We discuss implications across illnesses affecting the brain, including infection, major depressive disorder, stroke, Alzheimer's disease and type 2 diabetes.

  18. Specialised pro-resolving mediators of inflammation in inflammatory arthritis.

    PubMed

    Barden, Anne E; Moghaddami, Mahin; Mas, Emilie; Phillips, Michael; Cleland, Leslie G; Mori, Trevor A

    2016-04-01

    Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA. Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2.4g/day) for 4 weeks were studied. SPM in synovial fluid and plasma were measured by liquid chromatography-tandem mass spectrometry included 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of the E-series SPM (RvE1, RvE2, RvE3, 18R-RvE3), and 17-hydroxydocosahexaenoic acid (17-HDHA), the precursor of the D-series SPM (RvD1, 17R-RvD1, RvD2). Other SPM included protectin D1 (PD1), 10S,17S-dihydroxydocosahexaenoic acid (10,17S-DHDHA), maresin-1 (MaR-1) and 14-hydroxydocosahexaenoic acid (14-HDHA) derived from docosahexaenoic acid (DHA). E- and D-series SPM and the precursors 18-HEPE and 17-HDHA were present in synovial fluid and plasma of the patients with inflammatory arthritis. Plasma SPM were negatively related to erythrocyte sedimentation rate in arthritis patients (P<0.01) and synovial fluid RvE2 was negatively associated with pain score (P=0.02). Conversion from 18-HEPE and 17-HDHA to E- and D-series SPM was greater in synovial fluid (P<0.01). Most plasma SPM in arthritis patients were elevated (P<0.05) compared with healthy volunteers, and conversion to E- and D-series SPM was greater (P<0.01). SPM are present in chronic knee effusions and although the levels are lower than in plasma, the association between synovial fluid RvE2 and reduced pain scores suggests that synthesis of SPM at the site of inflammation is a relevant mechanism by which n-3FA alleviate the symptoms of arthritis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Resolving an inflammatory concept: The importance of inflammation and resolution in tendinopathy

    PubMed Central

    Dakin, Stephanie G.; Dudhia, Jayesh; Smith, Roger K.W.

    2014-01-01

    Injuries to the superficial digital flexor tendon (SDFT) are an important cause of morbidity and mortality in equine athletes, but the healing response is poorly understood. One important drive for the healing of connective tissues is the inflammatory cascade, but the role of inflammation in tendinopathy has been contentious in the literature. This article reviews the processes involved in the healing of tendon injuries in natural disease and experimental models. The importance of inflammatory processes known to be active in tendon disease is discussed with particular focus on recent findings related specifically to the horse. Whilst inflammation is necessary for debridement after injury, persistent inflammation is thought to drive fibrosis, a perceived adverse consequence of tendon healing. Therefore the ability to resolve inflammation by the resident cell populations in tendons at an appropriate time would be crucial for successful outcome. This review summarises new evidence for the importance of resolution of inflammation after tendon injury. Given that many anti-inflammatory drugs suppress both inflammatory and resolving components of the inflammatory response, prolonged use of these drugs may be contraindicated as a therapeutic approach. We propose that these findings have profound implications not only for current treatment strategies but also for the possibility of developing novel therapeutic approaches involving modulation of the inflammatory process. PMID:24556326

  20. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease.

    PubMed

    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

    2015-01-01

    To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study. Copyright © 2015 by the American College of Rheumatology.

  1. 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

  2. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus.

    PubMed

    Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis; Serafín-López, Jeanet; Estrada-García, Iris; Estrada-Parra, Sergio; Flores-Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

    2015-01-01

    Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice.

  3. Nonbilayer Phospholipid Arrangements Are Toll-Like Receptor-2/6 and TLR-4 Agonists and Trigger Inflammation in a Mouse Model Resembling Human Lupus

    PubMed Central

    Wong-Baeza, Carlos; Tescucano, Alonso; Astudillo, Horacio; Reséndiz, Albany; Landa, Carla; España, Luis; Serafín-López, Jeanet; Estrada-García, Iris; Estrada-Parra, Sergio; Flores-Romo, Leopoldo; Wong, Carlos; Baeza, Isabel

    2015-01-01

    Systemic lupus erythematosus is characterized by dysregulated activation of T and B cells and autoantibodies to nuclear antigens and, in some cases, lipid antigens. Liposomes with nonbilayer phospholipid arrangements induce a disease resembling human lupus in mice, including IgM and IgG antibodies against nonbilayer phospholipid arrangements. As the effect of these liposomes on the innate immune response is unknown and innate immune system activation is necessary for efficient antibody formation, we evaluated the effect of these liposomes on Toll-like receptor (TLR) signaling, cytokine production, proinflammatory gene expression, and T, NKT, dendritic, and B cells. Liposomes induce TLR-4- and, to a lesser extent, TLR-2/TLR-6-dependent signaling in TLR-expressing human embryonic kidney (HEK) cells and bone marrow-derived macrophages. Mice with the lupus-like disease had increased serum concentrations of proinflammatory cytokines, C3a and C5a; they also had more TLR-4-expressing splenocytes, a higher expression of genes associated with TRIF-dependent TLR-4-signaling and complement activation, and a lower expression of apoptosis-related genes, compared to healthy mice. The percentage of NKT and the percentage and activation of dendritic and B2 cells were also increased. Thus, TLR-4 and TLR-2/TLR-6 activation by nonbilayer phospholipid arrangements triggers an inflammatory response that could contribute to autoantibody production and the generation of a lupus-like disease in mice. PMID:26568960

  4. Is Alzheimer's Disease Autoimmune Inflammation of the Brain That Can be Treated With Nasal Nonsteroidal Anti-Inflammatory Drugs?

    PubMed

    Lehrer, Steven; Rheinstein, Peter H

    2015-05-01

    The Alzheimer's Association recently reported that a woman's estimated lifetime risk of developing Alzheimer's at age 65 is 1 in 6, compared to nearly 1 in 11 for a man (ie, female to male ratio 1.8). Based on female to male ratio, Alzheimer's disease could well be an autoimmune disorder. Like Alzheimer's, multiple sclerosis, an autoimmune inflammation of the central nervous system, has a female to male ratio of 2.3. Also based on female to male ratio, Alzheimer's resembles the autoimmune inflammatory disease rheumatoid arthritis, which has a female to male ratio of 2.7. The reasons for the female preponderance in autoimmune disease are unclear, but nonsteroidal anti-inflammatory drugs (NSAIDs) are widely and successfully employed to treat autoimmune anti-inflammatory disease and dramatically relieve symptoms. Moreover, oral NSAIDs consistently reduce the risk of Alzheimer's disease, although they have been totally ineffective as a treatment in multiple failed clinical trials. A basis for this failure might well be that the brain dose after oral administration is too small and not sufficiently early in the pathogenesis of the disorder. But NSAID brain dose could be significantly increased by delivering the NSAIDs intranasally.

  5. Therapeutics targeting inflammation in the immune reconstitution inflammatory syndrome.

    PubMed

    Shahani, Lokesh; Hamill, Richard J

    2016-01-01

    Immune reconstitution inflammatory syndrome (IRIS) is characterized by improvement in a previously incompetent human immune system manifesting as worsening of clinical symptoms secondary to the ability of the immune system to now mount a vigorous inflammatory response. IRIS was first recognized in the setting of human immunodeficiency virus, and this clinical setting continues to be where it is most frequently encountered. Hallmarks of the pathogenesis of IRIS, independent of the clinical presentation and the underlying pathogen, include excessive activation of the immune system, with increased circulating effector memory T cells, and elevated levels of serum cytokines and inflammatory markers. Patients with undiagnosed opportunistic infections remain at risk for unmasking IRIS at the time of active antiretroviral therapy (ART) initiation. Systematic screening for opportunistic infections before starting ART is a key element to prevent this phenomenon. Appropriate management of IRIS requires prompt recognition of the syndrome and exclusion of alternative diagnoses, particularly underlying infections and drug resistance. Controlled studies supporting the use of pharmacologic interventions in IRIS are scare, and recommendations are based on case series and expert opinions. The only controlled trial published to date, showed reduction in morbidity in patients with paradoxical tuberculosis-related IRIS with the use of oral corticosteroids. There are currently limited data to recommend other anti-inflammatory or immunomodulatory therapies that are discussed in this review, and further research is needed. Ongoing research regarding the immune pathogenesis of IRIS will likely direct future rational therapeutic approaches and clinical trials. Published by Elsevier Inc.

  6. The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro.

    PubMed

    Kasper, Jennifer Y; Hermanns, Maria Iris; Cavelius, Christian; Kraegeloh, Annette; Jung, Thomas; Danzebrink, Rolf; Unger, Ronald E; Kirkpatrick, Charles James

    The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease. We monitored the inflammatory responsiveness of the cells (release of IL-8, soluble intercellular adhesion molecule 1, and soluble E-selectin) after exposure to inflammatory stimuli (lipopolysaccharide, TNF-α, INF-γ, IL1-β) and a nanoparticle (Ba/Gd: coprecipitated BaSO4 and Gd(OH)3), generally used as contrast agents. The barrier integrity of the coculture was evaluated via the determination of transepithelial electrical resistance and the apparent permeability coefficient (Papp) of NaFITC. The behavior of the coculture Caco-1/ISO-HAS-1 was compared to the respective monocultures Caco-2 and ISO-HAS-1. Based on transepithelial electrical resistance, the epithelial barrier integrity of the coculture remained stable during incubation with all stimuli, whereas the Papp decreased after exposure to the cytokine mixture (TNF-α, INF-γ, IL1-β, and Ba/Gd). Both the endothelial and epithelial monocultures showed a high inflammatory response in both the upper and lower transwell-compartments. However, in the coculture, inflammatory mediators were only detected on the epithelial side and not on the endothelial side. Thus in the coculture, based on the Papp, the epithelial barrier appears to prevent a potential inflammatory overreaction in the underlying endothelial cells

  7. The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro

    PubMed Central

    Kasper, Jennifer Y; Hermanns, Maria Iris; Cavelius, Christian; Kraegeloh, Annette; Jung, Thomas; Danzebrink, Rolf; Unger, Ronald E; Kirkpatrick, Charles James

    2016-01-01

    The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease. We monitored the inflammatory responsiveness of the cells (release of IL-8, soluble intercellular adhesion molecule 1, and soluble E-selectin) after exposure to inflammatory stimuli (lipopolysaccharide, TNF-α, INF-γ, IL1-β) and a nanoparticle (Ba/Gd: coprecipitated BaSO4 and Gd(OH)3), generally used as contrast agents. The barrier integrity of the coculture was evaluated via the determination of transepithelial electrical resistance and the apparent permeability coefficient (Papp) of NaFITC. The behavior of the coculture Caco-1/ISO-HAS-1 was compared to the respective monocultures Caco-2 and ISO-HAS-1. Based on transepithelial electrical resistance, the epithelial barrier integrity of the coculture remained stable during incubation with all stimuli, whereas the Papp decreased after exposure to the cytokine mixture (TNF-α, INF-γ, IL1-β, and Ba/Gd). Both the endothelial and epithelial monocultures showed a high inflammatory response in both the upper and lower transwell-compartments. However, in the coculture, inflammatory mediators were only detected on the epithelial side and not on the endothelial side. Thus in the coculture, based on the Papp, the epithelial barrier appears to prevent a potential inflammatory overreaction in the underlying endothelial cells

  8. Haemostatic system in inflammatory bowel diseases: New players in gut inflammation

    PubMed Central

    Scaldaferri, Franco; Lancellotti, Stefano; Pizzoferrato, Marco; Cristofaro, Raimondo De

    2011-01-01

    Inflammation and coagulation constantly influence each other and are constantly in balance. Emerging evidence supports this statement in acute inflammatory diseases, such as sepsis, but it also seems to be very important in chronic inflammatory settings, such as inflammatory bowel disease (IBD). Patients with Crohn’s disease and ulcerative colitis have an increased risk of thromboembolic events, and several abnormalities concerning coagulation components occur in the endothelial cells of intestinal vessels, where most severe inflammatory abnormalities occur. The aims of this review are to update and classify the type of coagulation system abnormalities in IBD, and analyze the strict and delicate balance between coagulation and inflammation at the mucosal level. Recent studies on possible therapeutic applications arising from investigations on coagulation abnormalities associated with IBD pathogenesis will also be briefly presented and critically reviewed. PMID:21350708

  9. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators

    PubMed Central

    Serhan, Charles N.; Chiang, Nan; Van Dyke, Thomas E.

    2009-01-01

    Preface Active resolution of acute inflammation is a previously unrecognized interface between innate and adaptive immunity. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programmes that enable inflamed tissues to return to homeostasis. This Review presents newly uncovered cellular and molecular mechanisms for the resolution of inflammation, revealing key roles for eicosanoids, such as lipoxins, and new families of endogenous chemical mediators, termed resolvins and protectins. These mediators carry antiinflammatory and pro-resolution properties with leukocytes, protect organs and stimulate mucosal antimicrobial defence and clearance. Together, they control local inflammatory responses at multiple levels to stimulate resolution. PMID:18437155

  10. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation

    PubMed Central

    Schumacher, Michael A; Hedl, Matija; Abraham, Clara; Bernard, Jessica K; Lozano, Patricia R; Hsieh, Jonathan J; Almohazey, Dana; Bucar, Edie B; Punit, Shivesh; Dempsey, Peter J; Frey, Mark R

    2017-01-01

    Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process. In vitro, pro-inflammatory activation of cultured murine and human macrophages induced ErbB4 expression; in contrast, other ErbB family members were not induced in pro-inflammatory cells, and other innate immune lineages (dendritic cells, neutrophils) did not express detectable ErbB4 levels. Treatment of activated pro-inflammatory macrophages with the ErbB4 ligand neuregulin-4 (NRG4) induced apoptosis. ErbB4 localized to the mitochondria in these cells. Apoptosis was accompanied by loss of mitochondrial membrane potential, and was dependent upon the proteases that generate the cleaved ErbB4 intracellular domain fragment, suggesting a requirement for this fragment and mitochondrial pathway apoptosis. In vivo, ErbB4 was highly expressed on pro-inflammatory macrophages but not neutrophils during experimental DSS colitis in C57Bl/6 mice. Active inflammation in this model suppressed NRG4 expression, which may allow for macrophage persistence and ongoing inflammation. Consistent with this notion, NRG4 levels rebounded during the recovery phase, and administration of exogenous NRG4 during colitis reduced colonic macrophage numbers and ameliorated inflammation. These data define a novel role for ErbB4 in macrophage apoptosis, and outline a mechanism of feedback inhibition that may promote resolution of colitis. PMID:28230865

  11. A rapid and transient peripheral inflammatory response precedes brain inflammation after experimental stroke.

    PubMed

    Chapman, Katie Z; Dale, Verity Q; Dénes, Adám; Bennett, Gavin; Rothwell, Nancy J; Allan, Stuart M; McColl, Barry W

    2009-11-01

    Increasing evidence suggests that peripheral inflammatory responses to stroke and other brain injuries have an important role in determining neurological outcome. The mediators of this response and the temporal relationships between peripheral and central inflammatory alterations are poorly understood. In this study, we show that experimental stroke in mice induces a peripheral inflammatory response that peaks 4 h after stroke, and precedes the peak in brain inflammation 24 h after stroke. This peripheral response is dominated by the induction of the chemokine CXCL-1 and the proinflammatory cytokine interleukin-6 and could serve as an accessible target for therapy and as a source of biomarkers predictive of prognosis.

  12. Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases?

    PubMed

    Becker, Julien; Delayre-Orthez, Carine; Frossard, Nelly; Pons, Françoise

    2006-10-01

    Lung inflammatory diseases, such as acute lung injury (ALI), asthma, chronic obstructive pulmonary disease (COPD) and lung fibrosis, represent a major health problem worldwide. Although glucocorticoids are the most potent anti-inflammatory drug in asthma, they exhibit major side effects and have poor activity in lung inflammatory disorders such as ALI or COPD. Therefore, there is growing need for the development of alternative or new therapies to treat inflammation in the lung. Peroxisome proliferator-activated receptors (PPARs), including the three isotypes PPARalpha, PPARbeta (or PPARdelta) and PPARgamma, are transcription factors belonging to the nuclear hormone receptor superfamily. PPARs, and in particular PPARalpha and PPARgamma, are well known for their critical role in the regulation of energy homeostasis by controlling expression of a variety of genes involved in lipid and carbohydrate metabolism. Synthetic ligands of the two receptor isotypes, the fibrates and the thiazolidinediones, are clinically used to treat dyslipidaemia and type 2 diabetes, respectively. Recently however, PPARalpha and PPARgamma have been shown to exert a potent anti-inflammatory activity, mainly through their ability to downregulate pro-inflammatory gene expression and inflammatory cell functions. The present article reviews the current knowledge of the role of PPARalpha and PPARgamma in controlling inflammation, and presents different findings suggesting that PPARalpha and PPARgamma activators may be helpful in the treatment of lung inflammatory diseases.

  13. Thioredoxin Ameliorates Cutaneous Inflammation by Regulating the Epithelial Production and Release of Pro-Inflammatory Cytokines

    PubMed Central

    Tian, Hai; Matsuo, Yoshiyuki; Fukunaga, Atsushi; Ono, Ryusuke; Nishigori, Chikako; Yodoi, Junji

    2013-01-01

    Human thioredoxin-1 (TRX) is a 12-kDa protein with redox-active dithiol in the active site -Cys-Gly-Pro-Cys-. It has been demonstrated that systemic administration and transgenic overexpression of TRX ameliorate inflammation in various animal models, but its anti-inflammatory mechanism is not well characterized. We investigated the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX) in a murine irritant contact dermatitis (ICD) induced by croton oil. Topically applied rhTRX was distributed only in the skin tissues under both non-inflammatory and inflammatory conditions, and significantly suppressed the inflammatory response by inhibiting the production of cytokines and chemokines, such as TNF-α, Il-1β, IL-6, CXCL-1, and MCP-1. In an in vitro study, rhTRX also significantly inhibited the formation of cytokines and chemokines produced by keratinocytes after exposure to croton oil and phorbol 12-myristate 13-acetate. These results indicate that TRX prevents skin inflammation via the inhibition of local formation of inflammatory cytokines and chemokines. As a promising new approach, local application of TRX may be useful for the treatment of various skin and mucosal inflammatory disorders. PMID:24058364

  14. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

    PubMed Central

    Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis. PMID:26691857

  15. Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis.

    PubMed

    Affò, Silvia; Rodrigo-Torres, Daniel; Blaya, Delia; Morales-Ibanez, Oriol; Coll, Mar; Millán, Cristina; Altamirano, José; Arroyo, Vicente; Caballería, Joan; Bataller, Ramón; Ginès, Pere; Sancho-Bru, Pau

    2015-01-01

    Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4+ cells and a reduction in Th17 (CD4+IL17+) and mature dendritic (MHCII+CD11c+) cells recruitment. Clodronate depletion of macrophages in Ccr6-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.

  16. Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects.

    PubMed

    Kim, Chaekyun; Cha, Young-Nam

    2014-01-01

    Taurine is one of the most abundant non-essential amino acid in mammals and has many physiological functions in the nervous, cardiovascular, renal, endocrine, and immune systems. Upon inflammation, taurine undergoes halogenation in phagocytes and is converted to taurine chloramine (TauCl) and taurine bromamine. In the activated neutrophils, TauCl is produced by reaction with hypochlorite (HOCl) generated by the halide-dependent myeloperoxidase system. TauCl is released from activated neutrophils following their apoptosis and inhibits the production of inflammatory mediators such as, superoxide anion, nitric oxide, tumor necrosis factor-α, interleukins, and prostaglandins in inflammatory cells at inflammatory tissues. Furthermore, TauCl increases the expressions of antioxidant proteins, such as heme oxygenase 1, peroxiredoxin, thioredoxin, glutathione peroxidase, and catalase in macrophages. Thus, a central role of TauCl produced by activated neutrophils is to trigger the resolution of inflammation and protect macrophages and surrounding tissues from being damaged by cytotoxic reactive oxygen metabolites overproduced during inflammation. This is achieved by attenuating further production of proinflammatory cytokines and reactive oxygen metabolites and also by increasing the levels of antioxidant proteins that are able to scavenge and diminish the production of cytotoxic oxygen metabolites. These findings suggest that TauCl released from activated neutrophils may be involved in the recovery processes of cells affected by inflammatory oxidative stresses and thus TauCl could be used as a potential physiological agent to control pathogenic symptoms of chronic inflammatory diseases.

  17. Inflammatory Mechanisms Associated with Prostatic Inflammation and Lower Urinary Tract Symptoms

    PubMed Central

    St. Sauver, Jennifer L.; Jacobsen, Steven J.

    2009-01-01

    Inflammation is a common finding in histologic prostate specimens obtained from aging men, and accumulating data suggest that inflammation may play an important role in the development of benign prostatic hyperplasia (BPH), and the development and progression of lower urinary tract symptoms (LUTS). Inflammatory processes may contribute to prostatic enlargement directly through stimulation of prostate growth, or, alternatively, through decreasing prostatic apoptosis. Additionally, inflammatory processes may impact other components of the urogenital tract, such as the bladder, and contribute to the LUTS that may be experienced both in the presence and in the absence of prostate enlargement. Current research therefore offers clues about converging inflammatory pathways which may be targeted to improve treatment of BPH and/or LUTS as well as identifying potential targets for prevention of these syndromes. PMID:19809538

  18. Impact of physical activity on inflammation: effects on cardiovascular disease risk and other inflammatory conditions

    PubMed Central

    Cicero, Arrigo

    2012-01-01

    Since the 19th century, many studies have enlightened the role of inflammation in atherosclerosis, changing our perception of “vessel plaque due to oxidized lipoproteins”, similar to a “rusted pipe”, towards a disease with involvement of many cell types and cytokines with more complex mechanisms. Although “physical activity” and “physical exercise” are two terms with some differences in meaning, compared to sedentary lifestyle, active people have lower cardiovascular risk and lower inflammatory markers. Activities of skeletal muscle reveal “myokines” which have roles in both the immune system and adipose tissue metabolism. In vitro and ex-vivo studies have shown beneficial effects of exercise on inflammation markers. Meanwhile in clinical studies, some conflicting results suggested that type of activity, exercise duration, body composition, gender, race and age may modulate anti-inflammatory effects of physical exercise. Medical data on patients with inflammatory diseases have shown beneficial effects of exercise on disease activity scores, patient well-being and inflammatory markers. Although the most beneficial type of activity and the most relevant patient group for anti-inflammatory benefits are still not clear, studies in elderly and adult people generally support anti-inflammatory effects of physical activity and moderate exercise could be advised to patients with cardiovascular risk such as patients with metabolic syndrome. PMID:23185187

  19. Autophagy, inflammation and innate immunity in inflammatory myopathies.

    PubMed

    Cappelletti, Cristina; Galbardi, Barbara; Kapetis, Dimos; Vattemi, Gaetano; Guglielmi, Valeria; Tonin, Paola; Salerno, Franco; Morandi, Lucia; Tomelleri, Giuliano; Mantegazza, Renato; Bernasconi, Pia

    2014-01-01

    Autophagy has a large range of physiological functions and its dysregulation contributes to several human disorders, including autoinflammatory/autoimmune diseases such as inflammatory myopathies (IIMs). In order to better understand the pathogenetic mechanisms of these muscular disorders, we sought to define the role of autophagic processes and their relation with the innate immune system in the three main subtypes of IIM, specifically sporadic inclusion body myositis (sIBM), polymyositis (PM), dermatomyositis (DM) and juvenile dermatomyositis (JDM). We found that although the mRNA transcript levels of the autophagy-related genes BECN1, ATG5 and FBXO32 were similar in IIM and controls, autophagy activation in all IIM subgroups was suggested by immunoblotting results and confirmed by immunofluorescence. TLR4 and TLR3, two potent inducers of autophagy, were highly increased in IIM, with TLR4 transcripts significantly more expressed in PM and DM than in JDM, sIBM and controls, and TLR3 transcripts highly up-regulated in all IIM subgroups compared to controls. Co-localization between autophagic marker, LC3, and TLR4 and TLR3 was observed not only in sIBM but also in PM, DM and JDM muscle tissues. Furthermore, a highly association with the autophagic processes was observed in all IIM subgroups also for some TLR4 ligands, endogenous and bacterial HSP60, other than the high-mobility group box 1 (HMGB1). These findings indicate that autophagic processes are active not only in sIBM but also in PM, DM and JDM, probably in response to an exogenous or endogenous 'danger signal'. However, autophagic activation and regulation, and also interaction with the innate immune system, differ in each type of IIM. Better understanding of these differences may lead to new therapies for the different IIM types.

  20. Anti-inflammatory modulation of chronic airway inflammation in the murine house dust mite model.

    PubMed

    Ulrich, Kristina; Hincks, Jennifer S; Walsh, Roddy; Wetterstrand, E M Caroline; Fidock, Mark D; Sreckovic, Sasha; Lamb, David J; Douglas, Garry J; Yeadon, Michael; Perros-Huguet, Christelle; Evans, Steven M

    2008-08-01

    Asthma affects 300 million people worldwide and continues to be a major cause of morbidity and mortality. Disease relevant animal models of asthma are required for benchmarking of novel therapeutic mechanisms in comparison to established clinical approaches. We demonstrate that chronic exposure of mice to house dust mite (HDM) extract results in allergic airway inflammation, that can be significantly attenuated by therapeutic intervention with phosphodiesterase 4 inhibition and corticosteroid treatment. Female BALB/c mice were administered intranasally with HDM (Dermatophagoides pteronyssinus) extract daily for five weeks, and therapeutic intervention with anti-inflammatory treatment (dexamethasone 1 mg/kg subcutaneous once daily, prednisolone 10mg/kg orally twice daily, fluticasone 3, 10 and 30 microg intranasally twice daily, roflumilast 10 mg/kg orally twice daily and intranasally 10 and 30 microg twice daily) was initiated after three weeks of exposure. Chronic HDM extract exposure resulted in significant airway inflammation, demonstrated by bronchoalveolar lavage cell infiltration and lung tissue inflammatory gene expression by TaqMan low density array. Chronic steroid treatment significantly inhibited these parameters. In addition, roflumilast caused a significant reduction in airway inflammatory cell infiltration. We have demonstrated that chronic HDM-induced allergic inflammation can be significantly ameliorated by steroid treatment, and that phosphodiesterase 4 inhibition modulates inflammatory cell infiltration. Therefore, the murine HDM model may be a useful tool for evaluating new targets for the treatment of asthma.

  1. Acacia ferruginea inhibits inflammation by regulating inflammatory iNOS and COX-2.

    PubMed

    Sakthivel, Kunnathur Murugesan; Guruvayoorappan, Chandrasekaran

    2016-01-01

    Inflammation is a local defensive reaction of a host to cellular injury or infection. Prolonged inflammation can contribute to pathogenesis of many disorders. Identification of naturally occurring phytoconstituents that can suppress inflammatory mediators can lead to the discovery of anti-inflammatory therapeutics. Acacia ferruginea is used traditionally to treat numerous ailments including hemorrhage, irritable bowel syndrome and leprosy. The present study evaluated the anti-inflammatory activity of A. ferruginea extract against acute (carrageenan) and chronic (formaldehyde) inflammation in Balb/c mice. Pre-treatment with A. ferruginea extract (10 mg/kg BW) for 5 consecutive days via intraperitonial (IP) administration significantly inhibited subsequent induction of paw edema in both models; the effects were comparable to that of the standard drug indomethacin. The results also showed the A. ferruginea extract significantly inhibited nitric oxide (NO) synthesis and iNOS expression (as measured in serum), diminished inflammation in - and neutrophil infiltration to - the paw tissues and led to a reduction in the number of COX-2(+) immunoreative cells (as evidenced by histologic and immunohistochemical analyses) in the paws relative to those in paws of mice that received the irritants only. Further, in vitro studies showed the extract could significantly scavenge free radicals generated as in DPPH and NO radical generating assays. Taken together, the results showed that A. ferruginea extract imparted potent anti-oxidant and -inflammatory effects, in part by maintaining oxidative homeostasis, inhibiting NO synthesis and suppressing iNOS and COX-2 expression and so could potentially be exploited as a potential plant-based medication against inflammatory disorders.

  2. The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease.

    PubMed

    Targownik, Laura E; Sexton, Kathryn A; Bernstein, Matthew T; Beatie, Brooke; Sargent, Michael; Walker, John R; Graff, Lesley A

    2015-07-01

    Previous studies have demonstrated that stress is associated with increased disease activity in individuals with inflammatory bowel disease (IBD). The association between perceived stress and gastrointestinal inflammation is not well described. Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn's disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen's Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity. Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03-1.10 and 1.03-1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65-9.43), but not in CD (OR 0.98, 95% CI 0.51-1.88). Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

  3. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both.

    PubMed

    Koschmieder, S; Mughal, T I; Hasselbalch, H C; Barosi, G; Valent, P; Kiladjian, J-J; Jeryczynski, G; Gisslinger, H; Jutzi, J S; Pahl, H L; Hehlmann, R; Maria Vannucchi, A; Cervantes, F; Silver, R T; Barbui, T

    2016-05-01

    The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.

  4. The biochemical origin of pain: the origin of all pain is inflammation and the inflammatory response. Part 2 of 3 - inflammatory profile of pain syndromes.

    PubMed

    Omoigui, Sota

    2007-01-01

    Every pain syndrome has an inflammatory profile consisting of the inflammatory mediators that are present in the pain syndrome. The inflammatory profile may have variations from one person to another and may have variations in the same person at different times. The key to treatment of Pain Syndromes is an understanding of their inflammatory profile. Pain syndromes may be treated medically or surgically. The goal should be inhibition or suppression of production of the inflammatory mediators and inhibition, suppression or modulation of neuronal afferent and efferent (motor) transmission. A successful outcome is one that results in less inflammation and thus less pain. We hereby briefly describe the inflammatory profile for several pain syndromes including arthritis, back pain, neck pain, fibromyalgia, interstitial cystitis, migraine, neuropathic pain, complex regional pain syndrome/reflex sympathetic dystrophy (CRPS/RSD), bursitis, shoulder pain and vulvodynia. These profiles are derived from basic science and clinical research performed in the past by numerous investigators and serve as a foundation to be built upon by other researchers and will be updated in the future by new technologies such as magnetic resonance spectroscopy. Our unifying theory or law of pain states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain

  5. Anti-inflammatory effect of Ulmus davidiana Planch (Ulmaceae) on collagen-induced inflammation in rats.

    PubMed

    Song, In-Kwang; Kim, Kap-Sung; Suh, Seok-Jong; Kim, Myung-Sunny; Kwon, Dae Young; Kim, Sun-Lim; Kim, Cheorl-Ho

    2007-01-01

    Ulmus davidiana Planch (Ulmaceae) extract (UD) has long been known to have anti-inflammatory and anticancer activities. UD has been also known to have protective effects on damaged tissue, inflammation and bone among other functions. Effects of UD on inflammatory and immune responses and its mechanisms in collagen-induced inflammation (CII) rat were studied. Hind paw volumes of rats were measured by volume meter; lymphocyte proliferation, interleukin (IL)-1, IL-2, tumor necrosis factor (TNF)-α level was determined by 3-(4,5-2dimethylthiazal-2yl)2,5-diphenyltetrazoliumbromide assay. Antibodies to collagen type II (BC-II) were determined by enzyme-linked immunosorbent assay. There was a marked secondary inflammatory response in CII model, which accompanied with the decrease of body weight and the weight of immune organs simultaneously. The administration of UD (20, 80, 150mg/kg, intragastrically×10 days) inhibited the inflammatory response and restored body weight and the weight of immune organs of CII rats. Lymphocyte proliferation and IL-2 production of CII rats increases, together with IL-1 and TNF-α in peritoneal macrophages and synoviocytes. The administration of UD (20, 80, 150mg/kg, 10 days) reduced above changes significantly. UD had no effect on the concentration of antibodies to BC-II. From the results, it was concluded that UD possesses anti-inflammatory and immunoregulatory activities and has a therapeutic effect on CII rats.

  6. Anti-inflammatory effects of Asparagus cochinchinensis extract in acute and chronic cutaneous inflammation.

    PubMed

    Lee, Do Yeon; Choo, Byung Kil; Yoon, Taesook; Cheon, Myeong Sook; Lee, Hye Won; Lee, A Yeong; Kim, Ho Kyoung

    2009-01-12

    Although Asparagus cochinchinensis Merrill (Liliaceae) has long been used in traditional Korean and Chinese medicine to treat inflammatory diseases, the underlying mechanism(s) by which these effects are induced remains to be defined. We investigated the effects of 70% ethanolic extract from Asparagus cochinchinensis Merrill (ACE) on skin inflammation in mice. Production of pro-inflammatory cytokines (tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta), activation of myeloperoxidase, and histological assessment were examined in acute and chronic skin inflammation using 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear edema. We also performed acetic acid-induced vascular permeability test. ACE inhibited topical edema in the mouse ear, following administration at 200mg/kg (i.p.), leading to substantial reductions in skin thickness and tissue weight, inflammatory cytokine production, neutrophil-mediated myeloperoxidase (MPO) activity, and various histopathological indicators. Furthermore, ACE was effective at reducing inflammatory damage induced by chronic TPA exposure and evoked a significant inhibition of vascular permeability induced by acetic acid in mice. These results demonstrate that ACE is an effective anti-inflammatory agent in murine phorbol ester-induced dermatitis, and suggest that the compound may have therapeutic potential in a variety of immune-related cutaneous diseases.

  7. Interferons as components of the complex web of reactions sustaining inflammation in idiopathic inflammatory myopathies.

    PubMed

    De Paepe, Boel

    2015-07-01

    Evidence accumulates implicating interferons (IFNs) in the chronic inflammation associated with the idiopathic inflammatory mypathies (IM). Dermatomyositis in particular appears to display a strong IFN type 1 signature. Proposed pathogenic actions of IFNs include the upregulation of major histocompatibility complex class I on muscle fibres, and the induction of a plethora of pro-inflammatory factors, including cytokines and chemokines. This review brings together findings on IFNs and IFN-induced factors, sketching their roles in IM immunopathogenesis in general and dermatomyositis in particular, and offering a basis for exploring their potential therapeutic relevance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Anti-inflammatory effect of selenium nanoparticles on the inflammation induced in irradiated rats.

    PubMed

    El-Ghazaly, M A; Fadel, N; Rashed, E; El-Batal, A; Kenawy, S A

    2017-02-01

    Selenium (Se) has been reported to possess anti-inflammatory properties, but its bioavailability and toxicity are considerable limiting factors. The present study aimed to investigate the possible anti-inflammatory and analgesic effects of selenium nanoparticles (Nano-Se) on inflammation induced in irradiated rats. Paw volume and nociceptive threshold were measured in carrageenan-induced paw edema and hyperalgesia model. Leukocytic count, tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), thiobarbituric acid reactive substances (TBAR), and total nitrate/nitrite (NOx) were estimated in the exudate collected from 6 day old air pouch model. Irradiated rats were exposed to 6 Gy gamma (γ)-irradiation. Nano-Se were administered orally in a dose of 2.55 mg/kg once before carrageenan injection in the first model and twice in the second model. The paw volume but not the nociceptive response produced by carrageenan in irradiated rats was higher than that induced in non-irradiated rats. Nano-Se were effective in reducing the paw volume in non-irradiated and irradiated rats but it did not alter the nociceptive threshold. The inflammation induced in irradiated rats increased all the estimated parameters in the exudate whereas; Nano-Se decreased their elevation in non-irradiated and irradiated rats. Nano-Se possess a potential anti-inflammatory activity on inflammation induced in irradiated rats.

  9. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype.

    PubMed

    Chung, Sangwoon; Lee, Tae Jin; Reader, Brenda F; Kim, Ji Young; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Ballinger, Megan N; Qian, Feng; Rusu, Luiza; Chung, Hae Young; Unterman, Terry G; Croce, Carlo M; Christman, John W

    2016-04-05

    Inflammatory monocyte and tissue macrophages influence the initiation, progression, and resolution of type 2 immune responses, and alveolar macrophages are the most prevalent immune-effector cells in the lung. While we were characterizing the M1- or M2-like macrophages in type 2 allergic inflammation, we discovered that FoxO1 is highly expressed in alternatively activated macrophages. Although several studies have been focused on the fundamental role of FoxOs in hematopoietic and immune cells, the exact role that FoxO1 plays in allergic asthmatic inflammation in activated macrophages has not been investigated. Growing evidences indicate that FoxO1 acts as an upstream regulator of IRF4 and could have a role in a specific inflammatory phenotype of macrophages. Therefore, we hypothesized that IRF4 expression regulated by FoxO1 in alveolar macrophages is required for established type 2 immune mediates allergic lung inflammation. Our data indicate that targeted deletion of FoxO1 using FoxO1-selective inhibitor AS1842856 and genetic ablation of FoxO1 in macrophages significantly decreases IRF4 and various M2 macrophage-associated genes, suggesting a mechanism that involves FoxO1-IRF4 signaling in alveolar macrophages that works to polarize macrophages toward established type 2 immune responses. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, macrophage specific FoxO1 overexpression is associated with an accentuation of asthmatic lung inflammation, whereas pharmacologic inhibition of FoxO1 by AS1842856 attenuates the development of asthmatic lung inflammation. Thus, our study identifies a role for FoxO1-IRF4 signaling in the development of alternatively activated alveolar macrophages that contribute to type 2 allergic airway inflammation.

  10. FoxO1 regulates allergic asthmatic inflammation through regulating polarization of the macrophage inflammatory phenotype

    PubMed Central

    Chung, Sangwoon; Lee, Tae Jin; Reader, Brenda F.; Kim, Ji Young; Lee, Yong Gyu; Park, Gye Young; Karpurapu, Manjula; Ballinger, Megan N.; Qian, Feng; Rusu, Luiza; Chung, Hae Young; Unterman, Terry G.; Croce, Carlo M.; Christman, John W.

    2016-01-01

    Inflammatory monocyte and tissue macrophages influence the initiation, progression, and resolution of type 2 immune responses, and alveolar macrophages are the most prevalent immune-effector cells in the lung. While we were characterizing the M1- or M2-like macrophages in type 2 allergic inflammation, we discovered that FoxO1 is highly expressed in alternatively activated macrophages. Although several studies have been focused on the fundamental role of FoxOs in hematopoietic and immune cells, the exact role that FoxO1 plays in allergic asthmatic inflammation in activated macrophages has not been investigated. Growing evidences indicate that FoxO1 acts as an upstream regulator of IRF4 and could have a role in a specific inflammatory phenotype of macrophages. Therefore, we hypothesized that IRF4 expression regulated by FoxO1 in alveolar macrophages is required for established type 2 immune mediates allergic lung inflammation. Our data indicate that targeted deletion of FoxO1 using FoxO1-selective inhibitor AS1842856 and genetic ablation of FoxO1 in macrophages significantly decreases IRF4 and various M2 macrophage-associated genes, suggesting a mechanism that involves FoxO1-IRF4 signaling in alveolar macrophages that works to polarize macrophages toward established type 2 immune responses. In response to the challenge of DRA (dust mite, ragweed, and Aspergillus) allergens, macrophage specific FoxO1 overexpression is associated with an accentuation of asthmatic lung inflammation, whereas pharmacologic inhibition of FoxO1 by AS1842856 attenuates the development of asthmatic lung inflammation. Thus, our study identifies a role for FoxO1-IRF4 signaling in the development of alternatively activated alveolar macrophages that contribute to type 2 allergic airway inflammation. PMID:27007158

  11. Progression of perianeurysmal inflammation after endovascular aneurysm repair for inflammatory abdominal aortic and bilateral common iliac artery aneurysms.

    PubMed

    Igari, Kimihiro; Kudo, Toshifumi; Uchiyama, Hidetoshi; Toyofuku, Takahiro; Inoue, Yoshinori

    2015-02-01

    The use of endovascular aneurysm repair (EVAR) to treat inflammatory abdominal aortic aneurysms (IAAAs) has been reported, and this procedure appears to be preferable to open surgical repair because of intraoperative difficulties related to inflammation. We herein report a case of IAAA and bilateral inflammatory common iliac artery aneurysms that was successfully treated with bifurcated stent grafting. The perianeurysmal inflammation worsened postoperatively, requiring the placement of a ureteric stent. EVAR is feasible in cases of inflammatory aneurysms; however, the potential for an inflammatory response should be taken into account when considering the application of EVAR in patients with IAAA.

  12. IL-32: A Novel Pluripotent Inflammatory Interleukin, towards Gastric Inflammation, Gastric Cancer, and Chronic Rhino Sinusitis

    PubMed Central

    2016-01-01

    A vast variety of nonstructural proteins have been studied for their key roles and involvement in a number of biological phenomenona. Interleukin-32 is a novel cytokine whose presence has been confirmed in most of the mammals except rodents. The IL-32 gene was identified on human chromosome 16 p13.3. The gene has eight exons and nine splice variants, namely, IL-32α, IL-32β, IL-32γ, IL-32δ, IL-32ε, IL-32ζ, IL-32η, IL-32θ, and IL-32s. It was found to induce the expression of various inflammatory cytokines including TNF-α, IL-6, and IL-1β as well as macrophage inflammatory protein-2 (MIP-2) and has been reported previously to be involved in the pathogenesis and progression of a number of inflammatory disorders, namely, inflammatory bowel disease (IBD), gastric inflammation and cancer, rheumatoid arthritis, and chronic obstructive pulmonary disease (COPD). In the current review, we have highlighted the involvement of IL-32 in gastric cancer, gastric inflammation, and chronic rhinosinusitis. We have also tried to explore various mechanisms suspected to induce the expression of this extraordinary cytokine as well as various mechanisms of action employed by IL-32 during the mediation and progression of the above said problems. PMID:27143819

  13. The role of chronic inflammation in the development of gastrointestinal cancers: reviewing cancer prevention with natural anti-inflammatory intervention.

    PubMed

    Lee, Ho-Jae; Park, Jong-Min; Han, Young Min; Gil, Hong Kwon; Kim, Jinhyung; Chang, Ji Young; Jeong, Migyeong; Go, Eun-Jin; Hahm, Ki Baik

    2016-01-01

    Inflammatory mediators alter the local environment of tumors, known as the tumor microenvironment. Mechanistically, chronic inflammation induces DNA damage, but understanding this hazard may help in the search for new chemopreventive agents for gastrointestinal (GI) cancer which attenuate inflammation. In the clinic, GI cancer still remains a major cause of cancer-associated mortality, chemoprevention with anti-inflammatory agents is thought to be a realistic approach to reduce GI cancer. Proton pump inhibitors, monoclonal antibodies targeting tumor necrosis factor-alpha, anti-sense targeted smad7 and non-steroidal anti-inflammatory agents have been investigated for their potential to prevent inflammation-based GI cancer. Besides these, a wide variety of natural products have also shown potential for the prevention of GI cancer. In this review, the authors will provide insights to explain the mechanistic connection between inflammation and GI cancer, as well as describe a feasible cancer prevention strategy based on anti-inflammatory treatments.

  14. MODEL OF COLONIC INFLAMMATION: IMMUNE MODULATORY MECHANISMS IN INFLAMMATORY BOWEL DISEASE

    PubMed Central

    Wendelsdorf, Katherine; Bassaganya-Riera, Josep; Hontecillas, Raquel; Eubank, Stephen

    2010-01-01

    Inflammatory Bowel Disease (IBD) is an immunoinflammatory illness of the gut initiated by an immune response to bacteria in the microflora. The resulting immunopathogenesis leads to lesions in epithelial lining of the colon through which bacteria may infiltrate the tissue causing recurring bouts of diarrhea, rectal bleeding, and mal-nutrition. In healthy individuals such immunopathogenesis is avoided by the presence of regulatory cells that inhibit the inflammatory pathway. Highly relevant to the search for treatment strategies is the identification of components of the inflammatory pathway that allow regulatory mechanisms to be overridden and immunopathogenesis to proceed. In vitro techniques have identified cellular interactions involved in inflammation-regulation crosstalk. However, tracing immunological mechanisms discovered at the cellular level confidently back to an in vivo context of multiple, simultaneous interactions has met limited success. To explore the impact of specific interactions, we have constructed a system of 29 ordinary differential equations representing different phenotypes of T-cells, macrophages, dendritic cells, and epithelial cells as they move and interact with bacteria in the lumen, lamina propria, and lymphoid tissue of the colon. Simulations revealed the positive inflammatory feedback loop formed by inflammatory M1 macrophage activation of T-cells as a driving force underlying the immunopathology of IBD. Furthermore, strategies that remove M1 from the site of infection, by either i) increasing its potential to switch to a regulatory M2 phenotype or ii) increasing the rate of reversion (for M1 and M2 alike) to a resting state, cease immunopathogenesis even as bacteria are eliminated by other inflammatory cells. Based on these results, we identify macrophages and their mechanisms of plasticity as key targets for mucosal inflammation intervention strategies. In addition, we propose that the primary mechanism behind the association of

  15. Eicosapentaenoic acid attenuates cigarette smoke-induced lung inflammation by inhibiting ROS-sensitive inflammatory signaling

    PubMed Central

    Liu, Meng-Han; Lin, An-Hsuan; Lu, Shing-Hwa; Peng, Ruo-Yun; Lee, Tzong-Shyuan; Kou, Yu Ru

    2014-01-01

    Cigarette smoking causes chronic lung inflammation that is mainly regulated by redox-sensitive pathways. Our previous studies have demonstrated that cigarette smoke (CS) activates reactive oxygen species (ROS)-sensitive mitogen-activated protein kinases (MAPKs)/nuclear factor-κB (NF-κB) signaling resulting in induction of lung inflammation. Eicosapentaenoic acid (EPA), a major type of omega-3 polyunsaturated fatty acid, is present in significant amounts in marine-based fish and fish oil. EPA has been shown to possess antioxidant and anti-inflammatory properties in vitro and in vivo. However, whether EPA has similar beneficial effects against CS-induced lung inflammation remains unclear. Using a murine model, we show that subchronic CS exposure for 4 weeks caused pulmonary inflammatory infiltration (total cell count in bronchoalveolar lavage fluid (BALF), 11.0-fold increase), increased lung vascular permeability (protein level in BALF, 3.1-fold increase), elevated levels of chemokines (11.4–38.2-fold increase) and malondialdehyde (an oxidative stress biomarker; 2.0-fold increase) in the lungs, as well as lung inflammation; all of these CS-induced events were suppressed by daily supplementation with EPA. Using human bronchial epithelial cells, we further show that CS extract (CSE) sequentially activated NADPH oxidase (NADPH oxidase activity, 1.9-fold increase), increased intracellular levels of ROS (3.0-fold increase), activated both MAPKs and NF-κB, and induced interleukin-8 (IL-8; 8.2-fold increase); all these CSE-induced events were inhibited by pretreatment with EPA. Our findings suggest a novel role for EPA in alleviating the oxidative stress and lung inflammation induced by subchronic CS exposure in vivo and in suppressing the CSE-induced IL-8 in vitro via its antioxidant function and by inhibiting MAPKs/NF-κB signaling. PMID:25452730

  16. Tissue heme oxygenase-1 exerts anti-inflammatory effects on LPS-induced pulmonary inflammation.

    PubMed

    Konrad, F M; Knausberg, U; Höne, R; Ngamsri, K-C; Reutershan, J

    2016-01-01

    Heme oxygenase-1 (HO-1) has been shown to display anti-inflammatory properties in models of acute pulmonary inflammation. For the first time, we investigated the role of leukocytic HO-1 using a model of HO-1(flox/flox) mice lacking leukocytic HO-1 that were subjected to lipopolysaccharide (LPS)-induced acute pulmonary inflammation. Immunohistology and flow cytometry demonstrated that activation of HO-1 using hemin decreased migration of polymorphonuclear leukocytes (PMNs) to the lung interstitium and bronchoalveolar lavage (BAL) in the wild-type and, surprisingly, also in HO-1(flox/flox) mice, emphasizing the anti-inflammatory potential of nonmyeloid HO-1. Nevertheless, hemin reduced the CXCL1, CXCL2/3, tumor necrosis factor-α (TNFα), and interleukin 6 (IL6) levels in both animal strains. Microvascular permeability was attenuated by hemin in wild-type and HO-1(flox/flox) mice, indicating a crucial role of non-myeloid HO-1 in endothelial integrity. The determination of the activity of HO-1 in mouse lungs revealed no compensatory increase in the HO-1(flox/flox) mice. Topical administration of hemin via inhalation reduced the dose required to attenuate PMN migration and microvascular permeability by a factor of 40, emphasizing its clinical potential. In addition, HO-1 stimulation was protective against pulmonary inflammation when initiated after the inflammatory stimulus. In conclusion, nonmyeloid HO-1 is crucial for the anti-inflammatory effect of this enzyme on PMN migration to different compartments of the lung and on microvascular permeability.

  17. Accelerated resolution of inflammation underlies sex differences in inflammatory responses in humans

    PubMed Central

    Rathod, Krishnaraj S.; Kapil, Vikas; Velmurugan, Shanti; Khambata, Rayomand S.; Siddique, Umme; Khan, Saima; Van Eijl, Sven; Bansal, Jascharanpreet; Pitrola, Kavi; Shaw, Christopher; D’Acquisto, Fulvio; Colas, Romain A.; Marelli-Berg, Federica

    2016-01-01

    BACKGROUND. Cardiovascular disease occurs at lower incidence in premenopausal females compared with age-matched males. This variation may be linked to sex differences in inflammation. We prospectively investigated whether inflammation and components of the inflammatory response are altered in females compared with males. METHODS. We performed 2 clinical studies in healthy volunteers. In 12 men and 12 women, we assessed systemic inflammatory markers and vascular function using brachial artery flow-mediated dilation (FMD). In a further 8 volunteers of each sex, we assessed FMD response to glyceryl trinitrate (GTN) at baseline and at 8 hours and 32 hours after typhoid vaccine. In a separate study in 16 men and 16 women, we measured inflammatory exudate mediators and cellular recruitment in cantharidin-induced skin blisters at 24 and 72 hours. RESULTS. Typhoid vaccine induced mild systemic inflammation at 8 hours, reflected by increased white cell count in both sexes. Although neutrophil numbers at baseline and 8 hours were greater in females, the neutrophils were less activated. Systemic inflammation caused a decrease in FMD in males, but an increase in females, at 8 hours. In contrast, GTN response was not altered in either sex after vaccine. At 24 hours, cantharidin formed blisters of similar volume in both sexes; however, at 72 hours, blisters had only resolved in females. Monocyte and leukocyte counts were reduced, and the activation state of all major leukocytes was lower, in blisters of females. This was associated with enhanced levels of the resolving lipids, particularly D-resolvin. CONCLUSIONS. Our findings suggest that female sex protects against systemic inflammation-induced endothelial dysfunction. This effect is likely due to accelerated resolution of inflammation compared with males, specifically via neutrophils, mediated by an elevation of the D-resolvin pathway. TRIAL REGISTRATION. ClinicalTrials.gov NCT01582321 and NRES: City Road and Hampstead Ethics

  18. Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation.

    PubMed

    Bach-Rojecky, Lidija; Dominis, Mara; Lacković, Zdravko

    2008-10-01

    Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention. In the present paper, we investigate possible anti-inflammatory action of the toxin in carrageenan and capsaicin models of inflammation in rats. BTX-A (5 and 10 U/kg) was injected into the plantar surface of the rat right hind-paw pad 5 days before the injection of the carrageenan (1%) or capsaicin (0.1%) at the same site. Carrageenan-induced paw oedema and capsaicin-induced protein extravasation were measured. Control, inflamed and BTX-A pretreated inflamed paws were photographed and histopathological analysis (haematoxylin & eosin) was performed. Pretreatment with BTX-A had no effect on the size of carrageenan-induced paw oedema, measured as paw volume and weight or capsaicin-induced plasma extravasations, measured by Evans blue as a marker of protein leakage. Neither macroscopic nor microscopic analysis showed a significant difference between BTX-A pretreated and control inflamed tissue. Results show dissociation between the effect of BTX-A on pain and inflammation thus questioning the validity of the suggested assumption about the common peripheral mechanism of action.

  19. Adiponectin expression in patients with inflammatory cardiomyopathy indicates favourable outcome and inflammation control.

    PubMed

    Bobbert, Peter; Scheibenbogen, Carmen; Jenke, Alexander; Kania, Gabriele; Wilk, Sabrina; Krohn, Stefanie; Stehr, Jenny; Kuehl, Uwe; Rauch, Ursula; Eriksson, Urs; Schultheiss, Heinz Peter; Poller, Wolfgang; Skurk, Carsten

    2011-05-01

    Circulating adiponectin (APN) is an immunomodulatory, pro-angiogenic, and anti-apoptotic adipocytokine protecting against acute viral heart disease and preventing pathological remodelling after cardiac injury. The purpose of this study was to describe the regulation and effects of APN in patients with inflammatory cardiomyopathy (DCMi). Adiponectin expression and outcome were assessed in 173 patients with DCMi, 30 patients with non-inflammatory DCM, and 30 controls. Mechanistic background of these findings was addressed in murine experimental autoimmune myocarditis (EAM), a model of human DCMi, and further elucidated in vitro. Adiponectin plasma concentrations were significantly higher in DCMi compared with DCM or controls, i.e. 6.8 ± 3.9 µg/mL vs. 5.4 ± 3.6 vs. 4.76 ± 2.5 µg/mL (P< 0.05, respectively) and correlated significantly with cardiac mononuclear infiltrates (CD3+: r(2)= 0.025, P= 0.038; CD45R0+: r(2)= 0.058, P= 0.018). At follow-up, DCMi patients with high APN levels showed significantly increased left ventricular ejection fraction improvement, decreased left ventricular end-diastolic diameter, and reduced cardiac inflammatory infiltrates compared with patients with low APN levels. A multivariate linear regression analysis implicated APN as an independent prognostic factor for inhibition of cardiac inflammation. In accordance with these findings in human DCMi, EAM mice exhibited elevated plasma APN. Adiponectin gene transfer led to significant downregulation of key inflammatory mediators promoting disease. Mechanistically, APN acted as a negative regulator of T cells by reducing antigen specific expansion (P< 0.01) and suppressed TNFα-mediated NFκB activation (P< 0.01) as well as release of reactive oxygen species in cardiomyocytes. Our results implicate that APN acts as endogenously upregulated anti-inflammatory cytokine confining cardiac inflammation and progression in DCMi.

  20. Antioxidant modulation of skin inflammation: preventing inflammatory progression by inhibiting neutrophil influx

    PubMed Central

    McGilvray, Ian D.; Rotstein, Ori D.

    1999-01-01

    Objective To test the hypothesis that antioxidants might affect local inflammation by impairing inflammatory cell influx. Design A laboratory study using a Swiss–Webster mouse model of local inflammation. Setting A university-affiliated hospital. Methods Intradermal injection of 30 μg of S. minnesota endotoxin (LPS) to Swiss–Webster mice initiates a local inflammatory reaction characterized by an early rise in vascular permeability and a later influx of neutrophils. Animals were pretreated intraperitoneally with either pyrrolidine dithiocarbamate (PDTC, 2 mmol/kg), which inhibits free radical generation, or dimethylthiourea (DMTU, 450 mg/kg), a free radical scavenger. Main outcome measures Histologic findings of tissue samples taken at sites of injection; local changes in tissue vascular permeability (PI) determined by iodine-125 albumin injection before sacrifice; neutrophil accumulation quantified by tissue myeloperoxidase levels; tissue levels of the endothelial adhesion molecules intercellular adhesion molecule-1 protein (ICAM-1) and vascular cell adhesion molecule-1 protein (VCAM-1) assessed by immunohistochemistry and Western blot, respectively. Results Neither antioxidant had a significant effect on the early increase in PI, but both decreased the late rise in PI and reduced neutrophil influx. Both ICAM-1 and VCAM-1 were upregulated in response to LPS; however, only the increase in VCAM-1 was attenuated by antioxidant pretreatment. Conclusion These data suggest that antioxidants disrupt the propagation phase of an inflammatory response, possibly by altering neutrophil migration. PMID:10223071

  1. CD38 Is Expressed on Inflammatory Cells of the Intestine and Promotes Intestinal Inflammation

    PubMed Central

    Schneider, Michael; Schumacher, Valéa; Lischke, Timo; Lücke, Karsten; Meyer-Schwesinger, Catherine; Velden, Joachim; Koch-Nolte, Friedrich; Mittrücker, Hans-Willi

    2015-01-01

    The enzyme CD38 is expressed on a variety of hematopoietic and non-hematopoietic cells and is involved in diverse processes such as generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Here, we show that under homeostatic conditions CD38 is highly expressed on immune cells of the colon mucosa of C57BL/6 mice. Myeloid cells recruited to this tissue upon inflammation also express enhanced levels of CD38. To determine the role of CD38 in intestinal inflammation, we applied the dextran sulfate sodium (DSS) colitis model. Whereas wild-type mice developed severe colitis, CD38-/- mice had only mild disease following DSS-treatment. Histologic examination of the colon mucosa revealed pronounced inflammatory damage with dense infiltrates containing numerous granulocytes and macrophages in wild-type animals, while these findings were significantly attenuated in CD38-/- mice. Despite attenuated histological findings, the mRNA expression of inflammatory cytokines and chemokines was only marginally lower in the colons of CD38-/- mice as compared to wild-type mice. In conclusion, our results identify a function for CD38 in the control of inflammatory processes in the colon. PMID:25938500

  2. Anti-inflammatory effects of royal jelly on ethylene glycol induced renal inflammation in rats.

    PubMed

    Aslan, Zeyneb; Aksoy, Laçine

    2015-01-01

    In this study, anti-inflammatory effects of Royal Jelly were investigated by inducing renal inflammation in rats with the use of ethylene glycol. For this purpose, the calcium oxalate urolithiasis model was obtained by feeding rats with ethylene glycol in drinking water. The rats were divided in five study groups. The 1st group was determined as the control group. The rats in the 2nd group received ethylene glycol (1%) in drinking water. The rats in the 3rd group were daily fed with Royal Jelly by using oral gavage. The 4th group was determined as the preventive group and the rats were fed with ethylene glycol (1%) in drinking water while receiving Royal Jelly via oral gavage. The 5th group was determined as the therapeutic group and received ethylene glycol in drinking water during the first 2 weeks of the study and Royal Jelly via oral gavage during the last 2 weeks of the study. At the end of the study, proinflammatory/anti-inflammatory cytokines, TNF-a, IL-1ß and IL-18 levels in blood and renal tissue samples from the rats used in the application were measured. The results have shown that ethylene glycol does induce inflammation and renal damage. This can cause the formation of reactive oxygen species. Royal Jelly is also considered to have anti-inflammatory effects due to its possible antiradical and antioxidative effects. It can have positive effects on both the prevention of urolithiasis and possible inflammation during the existing urolithiasis and support the medical treatment.

  3. Fecal Microbiota in Pediatric Inflammatory Bowel Disease and Its Relation to Inflammation.

    PubMed

    Kolho, Kaija-Leena; Korpela, Katri; Jaakkola, Tytti; Pichai, Madharasi V A; Zoetendal, Erwin G; Salonen, Anne; de Vos, Willem M

    2015-06-01

    Inflammatory bowel disease (IBD) is considered to result from interplay between host and intestinal microbiota. While IBD in adults has shown to be associated with marked changes in the intestinal microbiota, there are only a few studies in children, and particularly studies focusing on therapeutic responses are lacking. Hence, this prospective study addressed the intestinal microbiota in pediatric IBD especially related to the level of inflammation. In total, 68 pediatric patients with IBD and 26 controls provided stool and blood samples in a tertiary care hospital and 32 received anti-tumor necrosis factor-α (anti-TNF-α). Blood inflammatory markers and fecal calprotectin levels were determined. The intestinal microbiota was characterized by phylogenetic microarray and qPCR analysis. The microbiota varied along a gradient of increasing intestinal inflammation (indicated by calprotectin levels), which was associated with reduced microbial richness, abundance of butyrate producers, and relative abundance of Gram-positive bacteria (especially Clostridium clusters IV and XIVa). A significant association between microbiota composition and inflammation was indicated by a set of bacterial groups predicting the calprotectin levels (area under curve (AUC) of 0.85). During the induction of anti-TNF-α, the microbial diversity and similarity to the microbiota of controls increased in the responder group by week 6, but not in the non-responders (P<0.01; response related to calprotectin levels). The abundance of six groups of bacteria including those related to Eubacterium rectale and Bifidobacterium spp. predicted the response to anti-TNF-α medication. Intestinal microbiota represents a potential biomarker for correlating the level of inflammation and therapeutic responses to be further validated.

  4. Genetics of acute inflammation: inflammatory reactions in inbred lines of mice and in their interline crosses.

    PubMed

    Stiffel, C; Ibanez, O M; Ribeiro, O G; Decreusefond, C; Mouton, D; Siqueira, M; Biozzi, G

    1990-01-01

    Acute inflammation is induced by the subcutaneous injection of swollen polyacrylamide microbeads, its intensity measured by the cell and protein concentration of the local exudates. A large and continuous range of responses is obtained in different inbred strains of mice, which suggests a polygenic control of the inflammatory response. The variable levels of the global dominance observed in F1 hybrids issued from several parental combinations indicated that the pattern of alleles controlling high or low response was different in each parental strain. Balanced intercrossing of the 8 inbred strains studied has provided a genetically heterogeneous F3 population, presenting a high variability of responses. The value of the genetic part of F3 phenotypic variance, the spread of the interstrain differences, as well as the polygenic nature of the regulation of inflammatory responses pointed out the possibility to perform a bidirectional genetic selection by using the F3 mice as the foundation population, and response to microbeads as the selective phenotypic character.

  5. Dietary inflammatory index is related to asthma risk, lung function and systemic inflammation in asthma

    PubMed Central

    Wood, Lisa G; Shivappa, Nitin; Berthon, Bronwyn S; Gibson, Peter G; Hebert, James R

    2014-01-01

    Background Asthma prevalence has increased in recent years and evidence suggests that diet may be a contributing factor. Increased use of processed foods has led to a decrease in diet quality, which may be creating a pro-inflammatory environment, thereby leading to the development and/or progression of various chronic inflammatory diseases and conditions. Recently, the Dietary Inflammatory Index (DII) has been developed and validated to assess the inflammatory potential of individual diets. Objective This study aimed to examine the DII in subjects with asthma compared to healthy controls and to relate the DII to asthma risk, lung function and systemic inflammation. Methods Subjects with asthma (n=99) and healthy controls (n=61) were recruited. Blood was collected and spirometry was performed. The DII was calculated from food frequency questionnaires administered to study subjects. Results The mean DII score for the asthmatics was higher than the DII score for healthy controls (−1.40 versus −1.86, p=0.04), indicating their diets were more pro-inflammatory. For every 1 unit increase in DII score the odds of having asthma increased by 70% (OR: 1.70, 95% CI: 1.03, 2.14; p=0.040). FEV1 was significantly associated with DII score (β=−3.44, 95% CI: −6.50,−0.39; p=0.020), indicating that for every 1 unit increase in DII score, FEV1 decreased by 3.44 times. Furthermore, plasma IL-6 concentrations were positively associated with DII score (β=0.13, 95% CI: 0.05, 0.21;p=0.002). Conclusion and clinical relevance As assessed using the DII score, the usual diet consumed by asthmatics in this study was pro-inflammatory relative to the diet consumed by the healthy controls. The DII score was associated with increased systemic inflammation and lower lung function. Hence, consumption of pro-inflammatory foods may contribute to worse asthma status and targeting an improvement in DII in asthmatics, as an indicator of suitable dietary intake, might be a useful strategy for

  6. Markers of inflammation, activation of blood platelets and coagulation disorders in inflammatory bowel diseases.

    PubMed

    Matowicka-Karna, Joanna

    2016-04-13

    Inflammatory bowel disease (IBD) includes ulcerative colitis and Crohn's disease. It is a group of chronic disorders characterized by inflammation of the gastrointestinal track with unknown etiology. Currently applied biomarkers include CRP, ESR, pANCA, ASCA, and fecal calprotectin. The etiopathogenesis of IBD is multifactorial. In patients with IBD in inflamed alimentary tract mucosa the number of recruited monocytes and activated macrophages which are source of cytokines. In IBD, the exacerbation is accompanied by thrombocytosis. Platelets play a crucial role in the hemostasis and inflammatory response. Selectins, which regulates the hemostasis and inflammatory response, stimulates the secretion of many inflammatory mediators such as β-thromboglobuline, CD40L, fibrinogen, IL-1β, platelet factor-4. In the course of IBD the following changes are observed: an increase in the number of platelets (reactive thrombocytosis), PDW and PCT, reduction in MPV, increased production and excretion of granular content products (P-selectin, GP53, β-TG, PF-4, vWF, fibrinolytic inhibitors).

  7. 4-Methoxycarbonyl Curcumin: A Unique Inhibitor of Both Inflammatory Mediators and Periodontal Inflammation

    PubMed Central

    Gu, Ying; Lee, Hsi-Ming; Napolitano, Nicole; Clemens, McKenzie; Zhang, Yazhou; Sorsa, Timo; Zhang, Yu; Johnson, Francis; Golub, Lorne M.

    2013-01-01

    Chronic inflammatory diseases such as periodontitis have been associated with increased risk for various medical conditions including diabetes and cardiovascular disease. Endotoxin (lipopolysaccharide, LPS), derived from gram-negative periodonto-pathogens, can induce the local accumulation of mononuclear cells in the inflammatory lesion, increasing proinflammatory cytokines and matrix metalloproteinases (MMPs). This ultimately results in the destruction of periodontal connective tissues including alveolar bone. Curcumin is the principal dyestuff in the popular Indian spice turmeric and has significant regulatory effects on inflammatory mediators but is characterized by poor solubility and low bioactivity. Recently, we developed a series of chemically modified curcumins (CMCs) with increased solubility and zinc-binding activity, while retaining, or further enhancing, their therapeutic effects. In the current study, we demonstrate that a novel CMC (CMC 2.5: 4-methoxycarbonyl curcumin) has significant inhibitory effects, better than the parent compound curcumin, on proinflammatory cytokines and MMPs in in vitro, in cell culture, and in an animal model of periodontal inflammation. The therapeutic potential of CMC 2.5 and its congeners may help to prevent tissue damage during various chronic inflammatory diseases including periodontitis and may reduce the risks of systemic diseases associated with this local disorder. PMID:24453415

  8. Coconut water of different maturity stages ameliorates inflammatory processes in model of inflammation

    PubMed Central

    Rao, Sadia Saleem; Najam, Rahila

    2016-01-01

    Aim: Coconut water is a natural beverage that is a part of daily diet of many people. This study was designed to explore the anti-inflammatory activity of coconut water of different maturation stages (young and mature) with rat paw edema model of inflammation using plethysmometer. Methodology: For this study, albino rats were selected and divided into four equal groups (10 rats in each group). Group 1 was set as control and administered distilled water 1 ml orally; Groups 2 and 3 were treated with young and mature coconut water, respectively, at 4 ml/100 g dose orally. Group 4 was treated with the standard drug (ibuprofen) at 400 mg/70 kg. 0.1 ml of 1% w/v acetic acid was administered in the subplantar tissue of rat paw 30 min after oral treatments of groups. Plethysmometer was used to measure rat paw edema. Results: Results revealed that both coconut water possess significant anti-inflammatory activity (P < 0.001). In comparison to control, percent inhibition by young coconut water was 20.22%, 35.13%, 42.52%, and 36% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (42.52%) was observed in the second phase of the inflammatory process. On the other hand, percent inhibition by mature coconut water was 18.80%, 25.94%, 24.13%, and 18.66% at 1, 2, 3, and 4 h of acetic acid administration, respectively. However, maximum percent inhibition (25.94%) was observed in the first phase of the inflammatory process. Conclusions: This study strongly suggests the use of young coconut water for potent anti-inflammatory effect and mature coconut water for moderate anti-inflammatory effect. PMID:27366350

  9. Molecular mechanisms of inflammation. Anti-inflammatory benefits of virgin olive oil and the phenolic compound oleocanthal.

    PubMed

    Lucas, Lisa; Russell, Aaron; Keast, Russell

    2011-01-01

    Chronic inflammation is a critical factor in the pathogenesis of many inflammatory disease states including cardiovascular disease, cancer, diabetes, degenerative joint diseases and neurodegenerative diseases. Chronic inflammatory states are poorly understood, however it is known that dietary habits can evoke or attenuate inflammatory responses. Popular methods to deal with inflammation and its associated symptoms involve the use of non steroidal anti-inflammatory drugs, however the use of these drugs are associated with severe side effects. Therefore, investigations concerned with natural methods of inflammatory control are warranted. A traditional Mediterranean diet has been shown to confer some protection against the pathology of chronic diseases through the attenuation of pro-inflammatory mediators and this has been partially attributed to the high intake of virgin olive oil accompanying this dietary regime. Virgin olive oil contains numerous phenolic compounds that exert potent anti-inflammatory actions. Of interest to this paper is the recently discovered phenolic compound oleocanthal. Oleocanthal is contained in virgin olive oil and possesses similar anti-inflammatory properties to ibuprofen. This pharmacological similarity has provoked interest in oleocanthal and the few studies conducted thus far have verified its anti-inflammatory and potential therapeutic actions. A review of the health benefits of the Mediterranean diet and anti-inflammatory properties of virgin olive oil is presented with the additional emphasis on the pharmacological and anti-inflammatory properties of the phenolic compound oleocanthal.

  10. Monogenic diseases associated with intestinal inflammation: implications for the understanding of inflammatory bowel disease.

    PubMed

    Uhlig, Holm H

    2013-12-01

    Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, has multifactorial aetiology with complex interactions between genetic and environmental factors. Over 150 genetic loci are associated with IBD. The genetic contribution of the majority of those loci towards explained heritability is low. Recent studies have reported an increasing spectrum of human monogenic diseases that can present with IBD-like intestinal inflammation. A substantial proportion of patients with those genetic defects present with very early onset of intestinal inflammation. The 40 monogenic defects with IBD-like pathology selected in this review can be grouped into defects in intestinal epithelial barrier and stress response, immunodeficiencies affecting granulocyte and phagocyte activity, hyper- and autoinflammatory disorders as well as defects with disturbed T and B lymphocyte selection and activation. In addition, there are defects in immune regulation affecting regulatory T cell activity and interleukin (IL)-10 signalling. Related to the variable penetrance of the IBD-like phenotype, there is a likely role for modifier genes and gene-environment interactions. Treatment options in this heterogeneous group of disorders range from anti-inflammatory and immunosuppressive therapy to blockade of tumour necrosis factor α and IL-1β, surgery, haematopoietic stem cell transplantation or gene therapy. Understanding of prototypic monogenic 'orphan' diseases cannot only provide treatment options for the affected patients but also inform on immunological mechanisms and complement the functional understanding of the pathogenesis of IBD.

  11. An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease

    PubMed Central

    Zhang, Sufeng; Ermann, Joerg; Succi, Marc D.; Zhou, Allen; Hamilton, Matthew J.; Cao, Bonnie; Korzenik, Joshua R.; Glickman, Jonathan N.; Vemula, Praveen K.; Glimcher, Laurie H.; Traverso, Giovanni; Langer, Robert; Karp, Jeffrey M.

    2016-01-01

    There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD. PMID:26268315

  12. Anti-inflammatory activity of Ajmodadi Churna extract against acute inflammation in rats

    PubMed Central

    Ram, H. N. Aswatha; Sriwastava, Neeraj K.; Makhija, Inder K.; Shreedhara, C. S.

    2012-01-01

    Background: Ayurvedic polyherbal formulations are widely prescribed for a wide range of inflammatory conditions, yet, despite widespread use, there has been no systematic documentation of their safety and efficacy. Objective: The present study was undertaken to evaluate the anti-inflammatory activity of aqueous extracts of Ajmodadi churna (AJM) in rats. Materials and Methods: Carrageenan-induced hind paw edema and air pouch inflammation models were used for the study. Results: The extracts showed significant antiinflammatory activity, reducing paw edema volume by 0.417 ± 0.097 and 0.379 ± 0.049, respectively. In the carrageenan-induced air pouch model, AJM reduced total leukocyte count by 73.09 ± 7.13 and 62.17 ± 10.53, granulocyte count by 69.48 ± 5.44 and 63.33 ± 4.13, and myeloperoxidase activity by 14.84 ± 0.91 and 18.44 ± 3.18, respectively, compared to controls. Discussion and Conclusion: AJM significantly reduced paw edema, during the second phase of edema development. In the carrageenan-induced air pouch model, AJM inhibited cellular infiltration into the air pouch fluid. We conclude that AJM is an effective candidate for prevention or treatment of acute inflammation PMID:22529678

  13. 'Neuroinflammation' differs categorically from inflammation: transcriptomes of Alzheimer's disease, Parkinson's disease, schizophrenia and inflammatory diseases compared.

    PubMed

    Filiou, Michaela D; Arefin, Ahmed Shamsul; Moscato, Pablo; Graeber, Manuel B

    2014-08-01

    'Neuroinflammation' has become a widely applied term in the basic and clinical neurosciences but there is no generally accepted neuropathological tissue correlate. Inflammation, which is characterized by the presence of perivascular infiltrates of cells of the adaptive immune system, is indeed seen in the central nervous system (CNS) under certain conditions. Authors who refer to microglial activation as neuroinflammation confuse this issue because autoimmune neuroinflammation serves as a synonym for multiple sclerosis, the prototypical inflammatory disease of the CNS. We have asked the question whether a data-driven, unbiased in silico approach may help to clarify the nomenclatorial confusion. Specifically, we have examined whether unsupervised analysis of microarray data obtained from human cerebral cortex of Alzheimer's, Parkinson's and schizophrenia patients would reveal a degree of relatedness between these diseases and recognized inflammatory conditions including multiple sclerosis. Our results using two different data analysis methods provide strong evidence against this hypothesis demonstrating that very different sets of genes are involved. Consequently, the designations inflammation and neuroinflammation are not interchangeable. They represent different categories not only at the histophenotypic but also at the transcriptomic level. Therefore, non-autoimmune neuroinflammation remains a term in need of definition.

  14. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation.

    PubMed

    Singh, Tej Pratap; Zhang, Howard H; Borek, Izabela; Wolf, Peter; Hedrick, Michael N; Singh, Satya P; Kelsall, Brian L; Clausen, Bjorn E; Farber, Joshua M

    2016-12-16

    Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells.

  15. Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation

    PubMed Central

    Singh, Tej Pratap; Zhang, Howard H.; Borek, Izabela; Wolf, Peter; Hedrick, Michael N.; Singh, Satya P.; Kelsall, Brian L.; Clausen, Bjorn E.; Farber, Joshua M.

    2016-01-01

    Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6Chi blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod. Moreover, we find that IL-23-induced inflammation requires expression of CCR6 by DCs or their precursors, and that CCR6 mediates monocyte trafficking into inflamed skin. Collectively, our results imply that monocyte-derived cells are critical contributors to psoriasis through production of inflammatory cytokines that augment the activation of skin T cells. PMID:27982014

  16. An inflammation-targeting hydrogel for local drug delivery in inflammatory bowel disease.

    PubMed

    Zhang, Sufeng; Ermann, Joerg; Succi, Marc D; Zhou, Allen; Hamilton, Matthew J; Cao, Bonnie; Korzenik, Joshua R; Glickman, Jonathan N; Vemula, Praveen K; Glimcher, Laurie H; Traverso, Giovanni; Langer, Robert; Karp, Jeffrey M

    2015-08-12

    There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.

  17. Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood.

    PubMed

    Connaughton, Ruth M; McMorrow, Aoibheann M; McGillicuddy, Fiona C; Lithander, Fiona E; Roche, Helen M

    2016-05-01

    Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

  18. Anti-inflammatory activity of Ailanthus altissima in ovalbumin-induced lung inflammation.

    PubMed

    Jin, Mei Hua; Yook, Jumin; Lee, Eunkyung; Lin, Chang Xin; Quan, Zhejiu; Son, Kun Ho; Bae, Ki Hwan; Kim, Hyun Pyo; Kang, Sam Sik; Chang, Hyeun Wook

    2006-05-01

    As part of an ongoing investigation to find bioactive medicinal herbs exerting anti-inflammation activity, the effect of an ethanol extract from the parts of Ailanthus altissima (Simaroubaceae) was evaluated in both in vitro and in in vivo system. The ethanol extract of A. altissima (EAa) inhibited generation of the cyclooxygenase-2 (COX-2) dependent phases of prostaglandin D2 in bone marrow-derived mast cells (BMMC) in a concentration-dependent manner with an IC50 value of 214.6 microg/ml. However, this compound did not inhibit COX-2 protein expression up to a concentration of 400 microg/ml in the BMMC, indicating that EAa directly inhibits COX-2 activity. In addition, EAa inhibited leukotriene C4 production with an IC50 value of 25.7 microg/ml. Furthermore, this compound inhibited degranulation reaction in a dose dependent manner, with an IC50 value of 27.3 microg/ml. Ovalbumin (OVA)-sensitized mice were orally pretreated with EAa before aerosol challenges. EAa reduced the eosinophil infiltration into the airway and the eotaxin, IL-4, and IL-13 mRNA expression levels. These results suggest that the anti-inflammation activity of A. altissima in OVA-induced lung inflammation may occur in part via the down regulation of T(H)2 cytokines and eotaxin transcripts as well as the inhibition of inflammatory mediators.

  19. Bioelectrical Stimulation for the Reduction of Inflammation in Inflammatory Bowel Disease

    PubMed Central

    Marshall, Ryan; Taylor, Ian; Lahr, Christopher; Abell, Thomas L.; Espinoza, Ingrid; Gupta, Nitin K.; Gomez, Christian R.

    2015-01-01

    Crohn’s disease and ulcerative colitis are the primary inflammatory bowel diseases (IBDs) affecting the gastrointestinal tract. The current therapy aims at decreasing inflammation and reducing symptoms. This typically requires immune suppression by steroids, thiopurines, methotrexate, or tumor necrosis factor inhibitors. Patients may be unreceptive to medical therapy, and some may discontinue the treatment due to adverse effects. Noninvasive, transcutaneous vagus nerve stimulation (VNS) is currently used as a treatment for depression and epilepsy, and it is being investigated for the treatment of conditions such as multiple sclerosis, migraines, and Alzheimer’s disease. Recent studies have demonstrated the importance of splenic and vagus nerve functions in the inflammatory process through the production of certain cytokines. We hypothesize that using transcutaneous VNS via the auricular afferent branch could achieve a selective anti-inflammatory effect on the intestinal wall. This review examines the possibility of using vagal stimulators as a therapy for IBD. This could open the door to novel treatments for numerous vagally mediated diseases characterized by poor responses to current therapies. PMID:26692766

  20. Metabolic syndrome, inflammation and atherosclerosis - the role of adipokines in health and in systemic inflammatory rheumatic diseases.

    PubMed

    Santos, Maria José; Fonseca, João Eurico

    2009-01-01

    Cardiovascular (CV) events are among the leading causes of morbidity and mortality in patients with inflammatory rheumatic diseases. It has been hypothesized that, in addition to the traditional CV risk factors, inflammation is a major contributor to atherogenesis. Metabolic syndrome (MetS) stands for a cluster of risk factors associated with insulin resistance and increased abdominal fat. Inflammation and MetS are intimately linked. Inflammatory biomarkers are frequently elevated in people with MetS and, conversely, the prevalence of MetS is higher in patients with chronic inflammatory rheumatic diseases, such as Rheumatoid Arthritis and Systemic Lupus Erythematosus. Inflammatory cytokines impair insulin sensitivity and can induce an adverse lipoprotein profile as seen in MetS. Furthermore, the presence of MetS correlates with increased subclinical atherosclerosis, major adverse CV events and death, making an important contribution to the CV burden in inflammatory diseases. Adipose tissue has recently emerged as an active organ that produces and secretes numerous mediators - adipokines - particularly relevant in energy homeostasis, inflammation, immune regulation and angiogenesis. These mediators arise as a potential link between MetS, inflammation and atherogenesis. Understanding the complex regulation and function of adipokines in health and disease is a priority since it may lead to new preventive and therapeutic interventions aiming to decrease CV risk.

  1. Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer

    PubMed Central

    Rubin, Deborah C.; Shaker, Anisa; Levin, Marc S.

    2012-01-01

    The inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of the gastrointestinal tract, from mouth to anus, but most commonly involves the distal part of the small intestine or ileum, and colon. UC results in colonic inflammation that can affect the rectum only, or can progress proximally to involve part of or the entire colon. Clinical symptoms include diarrhea, abdominal pain, gastrointestinal bleeding, and weight loss. A serious long-term complication of chronic inflammation is the development of colorectal cancer. A genetic basis for IBD had long been recognized based on the increased familial risk. However, significant discordance for CD in twins, and a much less robust phenotypic concordance for UC, suggested additional factors play a role in disease pathogenesis, including environmental factors. In the past several years, progress in understanding the molecular basis of IBD has accelerated, beginning with the generation of animal models of colitis and progressing to the identification of specific genetic markers from candidate gene, gene linkage, and genome-wide association analyses. Genetic studies have also resulted in the recognition of the importance of environmental factors, particularly the crucial role of the gut microbiota in CD and UC. Altered immune responses to the normal intestinal flora are key factors in IBD pathogenesis. In this research topic, the genetic basis of IBD, the genetic and cellular alterations associated with colitis-associated colon cancer, and the emerging role of the intestinal microbiota and other environmental factors will be reviewed. PMID:22586430

  2. A moderate aseptic local inflammation does not induce a significant systemic inflammatory response.

    PubMed

    Bauer, Natali; Mensinger, Sandra; Daube, Gert; Failing, Klaus; Moritz, Andreas

    2012-08-01

    The aim of this prospective study was to characterize the response of the coagulation system to a defined sterile localized inflammatory process. Tissue cages were implanted subcutaneously in five healthy Beagles. After 9-10 weeks, local inflammation was induced by an injection of 0.5 ml 1% carrageenan. Serial samples of tissue cage fluid (TCF) and blood were collected at 10 time points (0-168 h). Nucleated cells (NC) of TCF were counted automatically to characterize local inflammation. C-reactive protein (CRP), leukocytes and coagulation variables (PT, aPTT, fibrinogen, factor VIII, antithrombin, protein C, protein S, and d-dimers) were determined in blood samples. Carrageenan induced a significant 32-fold increase of NCs in TCF (P<0.0001). A slight increase in leukocytes (P<0.0001) was observed. There was a significant 1.3- to 1.5-fold increase in protein C (P=0.0001) and protein S (P=0.0028). CRP, secondary hemostasis and fibrinolysis did not change. The mild increase from baseline in PC/PS, may reflect a physiological counter reaction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation

    PubMed Central

    Gobbato, Nathália Brandão; de Souza, Flávia Castro Ribas; Fumagalli, Stella Bruna Napolitano; Lopes, Fernanda Degobbi Tenório Quirino dos Santos; Prado, Carla Máximo; Martins, Milton Arruda; Tibério, Iolanda de Fátima Lopes Calvo; Leick, Edna Aparecida

    2013-01-01

    Aims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-κB, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-κB positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response. PMID:24151607

  4. Adipocytokine orosomucoid integrates inflammatory and metabolic signals to preserve energy homeostasis by resolving immoderate inflammation.

    PubMed

    Lee, Yun Sok; Choi, Jin Woo; Hwang, Injae; Lee, Joo Won; Lee, Jae Ho; Kim, A Young; Huh, Jin Young; Koh, Young Jun; Koh, Gou Young; Son, Hee Jung; Masuzaki, Hiroaki; Hotta, Kikuko; Alfadda, Assim A; Kim, Jae Bum

    2010-07-16

    Orosomucoid (ORM), also called alpha-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-alpha, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-kappaB and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-alpha-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction.

  5. DNA methylation profile of genes involved in inflammation and autoimmunity in inflammatory bowel disease.

    PubMed

    Karatzas, Pantelis S; Mantzaris, Gerassimos J; Safioleas, Michael; Gazouli, Maria

    2014-12-01

    The contribution of epigenetic alterations to disease pathogenesis is emerging as a research priority. In this study, we aimed to seek DNA methylation changes in peripheral blood and tissue biopsies from patients with inflammatory bowel disease. The promoter methylation status of genes involved in inflammation and autoimmunity was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. Methylation was considered to be hypermethylated if >20% according to the instructions of the manufacturer. The microarrays were validated with Quantitative Real-time PCR. Regarding Crohn disease (CD) no gene appeared hypermethylated compared to healthy controls. In ulcerative colitis (UC) 5 genes (CXCL14, CXCL5, GATA3, IL17C, and IL4R) were hypermethylated compared to healthy controls. Some of the examined genes show different methylation patterns between CD and UC. Concerning tissue samples we found that all hypermethylated genes appear the same methylation pattern and confirmed a moderate-strong correlation between methylation levels in colon biopsies and peripheral blood (Pearson coefficients r=0.089-0.779, and r=0.023-0.353, respectively). The epigenetic changes observed in this study indicate that CD and UC exhibit specific DNA methylation signatures with potential clinical applications in IBD non-invasive diagnosis and prognosis.

  6. Metabonomic analysis of the anti-inflammatory effects of volatile oils of Angelica sinensis on rat model of acute inflammation.

    PubMed

    Zhang, Wen-Quan; Hua, Yong-Li; Zhang, Man; Ji, Peng; Li, Jin-Xia; Zhang, Ling; Li, Peng-Ling; Wei, Yan-Ming

    2015-06-01

    Metabonomics based on GC-MS was used to study the possible anti-inflammatory mechanisms of volatile oils of Angelica sinensis (VOAS) in rats with acute inflammation. Acute inflammation was induced by subcutaneous injection of carrageenan in rats. The levels of prostaglandin E2 (PGE2 ), histamine (HIS) and 5-hydroxytryptamine (5-HT) in the inflammatory fluid were detected. Principal component analysis and orthogonal partial least squares-discriminant analysis models were performed for pattern recognition analysis. After the administration of VOAS, the levels of PGE2 , HIS, and 5-HT returned to levels observed in normal group. According to GC-MS analysis, the intervention of VOAS in rats with acute inflammation induced substantial and characteristic changes in their metabolic profiles. Fourteen metabolite biomarkers, namely, lactic acid, malic acid, citric acid, trans-dehydroandrosterone, aldosterone, linoleic acid, hexadecanoic acid, pregnenolone, octadecenoic acid, myristic acid, l-histidine, octadecanoic acid, arachidonic acid (AA) and l-tryptophan, were detected in the inflammatory fluid. The levels of all biomarkers either increased or decreased significantly in model groups. VOAS possibly intervened in the metabolic process of inflammation by altering histidine metabolism, tryptophan metabolism, AA metabolism, steroid hormone biosynthesis, fatty acid metabolism and energy metabolism. Metabonomics was used to reflect an organism's physiological and metabolic state comprehensively, and it is a potentially powerful tool that reveals the anti-acute-inflammatory mechanism of VOAS. Copyright © 2014 John Wiley & Sons, Ltd.

  7. BZ-26, a novel GW9662 derivate, attenuated inflammation by inhibiting the differentiation and activation of inflammatory macrophages.

    PubMed

    Bei, Yuncheng; Chen, Jiajia; Zhou, Feifei; Huang, Yahong; Jiang, Nan; Tan, Renxiang; Shen, Pingping

    2016-12-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is considered to be an important transcriptional factor in regulation of macrophages differentiation and activation. We have synthesized a series of novel structural molecules based on GW9662's structure (named BZ-24, BZ-25 and BZ-26), and interaction activity was calculated by computational docking. BZ-26 had shown stronger interaction with PPARγ and had higher transcriptional inhibitory activity of PPARγ with lower dosage compared with GW9662. BZ-26 was proved to inhibit inflammatory macrophage differentiation. LPS-induced acute inflammation mouse model was applied to demonstrate its anti-inflammatory activity. And the results showed that BZ-26 administration attenuated plasma tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) secretion, which are vital cytokines in acute inflammation. The anti-inflammatory activity was examined in THP-1 cell line, and TNF-α, IL-6 and MCP-1, were significantly inhibited. The results of Western blot and luciferase reporter assay indicated that BZ-26 not only inhibited NF-κB transcriptional activity, but also abolished LPS-induce nuclear translocation of P65. We also test BZ-26 action in tumor-bearing chronic inflammation mouse model, and BZ-26 was able to alter macrophages phenotype, resulting in antitumor effect. All our data revealed that BZ-26 modulated LPS-induced acute inflammation via inhibiting inflammatory macrophages differentiation and activation, potentially via inhibition of NF-κB signal pathway.

  8. Docosahexaenoic Acid, Inflammation, and Bacterial Dysbiosis in Relation to Periodontal Disease, Inflammatory Bowel Disease, and the Metabolic Syndrome

    PubMed Central

    Tabbaa, Maria; Golubic, Mladen; Roizen, Michael F.; Bernstein, Adam M.

    2013-01-01

    Docosahexaenoic acid (DHA), a long-chain omega-3 polyunsaturated fatty acid, has been used to treat a range of different conditions, including periodontal disease (PD) and inflammatory bowel disease (IBD). That DHA helps with these oral and gastrointestinal diseases in which inflammation and bacterial dysbiosis play key roles, raises the question of whether DHA may assist in the prevention or treatment of other inflammatory conditions, such as the metabolic syndrome, which have also been linked with inflammation and alterations in normal host microbial populations. Here we review established and investigated associations between DHA, PD, and IBD. We conclude that by beneficially altering cytokine production and macrophage recruitment, the composition of intestinal microbiota and intestinal integrity, lipopolysaccharide- and adipose-induced inflammation, and insulin signaling, DHA may be a key tool in the prevention of metabolic syndrome. PMID:23966110

  9. Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution.

    PubMed

    Kataru, Raghu P; Jung, Keehoon; Jang, Cholsoon; Yang, Hanseul; Schwendener, Reto A; Baik, Jung Eun; Han, Seung Hyun; Alitalo, Kari; Koh, Gou Young

    2009-05-28

    Using a bacterial pathogen-induced acute inflammation model in the skin, we defined the roles of local lymphatic vessels and draining lymph nodes (DLNs) in antigen clearance and inflammation resolution. At the peak day of inflammation, robust expansion of lymphatic vessels and profound infiltration of CD11b+/Gr-1+ macrophages into the inflamed skin and DLN were observed. Moreover, lymph flow and inflammatory cell migration from the inflamed skin to DLNs were enhanced. Concomitantly, the expression of lymphangiogenic growth factors such as vascular endothelial growth factor C (VEGF-C), VEGF-D, and VEGF-A were significantly up-regulated in the inflamed skin, DLNs, and particularly in enriched CD11b+ macrophages from the DLNs. Depletion of macrophages, or blockade of VEGF-C/D or VEGF-A, largely attenuated these phenomena, and produced notably delayed antigen clearance and inflammation resolution. Conversely, keratin 14 (K14)-VEGF-C transgenic mice, which have dense and enlarged lymphatic vessels in the skin dermis, exhibited accelerated migration of inflammatory cells from the inflamed skin to the DLNs and faster antigen clearance and inflammation resolution. Taken together, these results indicate that VEGF-C, -D, and -A derived from the CD11b+/Gr-1+ macrophages and local inflamed tissues play a critical role in promoting antigen clearance and inflammation resolution.

  10. Central activation of the cholinergic anti-inflammatory pathway reduces surgical inflammation in experimental post-operative ileus.

    PubMed

    The, Fo; Cailotto, C; van der Vliet, J; de Jonge, W J; Bennink, R J; Buijs, R M; Boeckxstaens, G E

    2011-07-01

    Electrical stimulation of the vagus nerve reduces intestinal inflammation following mechanical handling, thereby shortening post-operative ileus in mice. Previous studies in a sepsis model showed that this cholinergic anti-inflammatory pathway can be activated pharmacologically by central administration of semapimod, an inhibitor of p38 mitogen-activated protein kinase. We therefore evaluated the effect of intracerebroventricular (i.c.v.) semapimod on intestinal inflammation and post-operative ileus in mice. Mice underwent a laparotomy or intestinal manipulation 1 h after i.c.v. pre-treatment with semapimod (1 µg·kg(-1) ) or saline. Drugs were administered through a cannula placed in the left lateral ventricle 1 week prior to experimentation. Twenty-four hours after surgery, gastric emptying was measured using scintigraphy, and the degree of intestinal inflammation was assessed. Finally, activation of brain regions was assessed using quantitative immunohistochemistry for c-fos. Intestinal manipulation induced inflammation of the manipulated intestine and significantly delayed gastric emptying, 24 h after surgery in saline-treated animals. Semapimod significantly reduced this inflammation and improved gastric emptying. Vagotomy enhanced the inflammatory response induced by intestinal manipulation and abolished the anti-inflammatory effect of semapimod. Semapimod but not saline induced a significant increase in c-fos expression in the paraventricular nucleus, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. Our findings show that i.c.v. semapimod reduces manipulation-induced intestinal inflammation and prevented post-operative ileus. This anti-inflammatory effect depends on central activation of the vagus nerve. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  11. Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.

    PubMed

    Wolfs, Tim G A M; Kramer, Boris W; Thuijls, Geertje; Kemp, Matthew W; Saito, Masatoshi; Willems, Monique G M; Senthamarai-Kannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

    2014-03-01

    Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO(+), CD3(+), and FoxP3(+) cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses.

  12. Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation

    PubMed Central

    Wolfs, Tim G. A. M.; Kramer, Boris W.; Thuijls, Geertje; Kemp, Matthew W.; Saito, Masatoshi; Willems, Monique G. M.; Senthamarai-Kannan, Paranthaman; Newnham, John P.; Jobe, Alan H.

    2014-01-01

    Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO+, CD3+, and FoxP3+ cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses. PMID:24458021

  13. Facial resemblance enhances trust.

    PubMed

    DeBruine, Lisa M

    2002-07-07

    Organisms are expected to be sensitive to cues of genetic relatedness when making decisions about social behaviour. Relatedness can be assessed in several ways, one of which is phenotype matching: the assessment of similarity between others' traits and either one's own traits or those of known relatives. One candidate cue of relatedness in humans is facial resemblance. Here, I report the effects of an experimental manipulation of facial resemblance in a two-person sequential trust game. Subjects were shown faces of ostensible playing partners manipulated to resemble either themselves or an unknown person. Resemblance to the subject's own face raised the incidence of trusting a partner, but had no effect on the incidence of selfish betrayals of the partner's trust. Control subjects playing with identical pictures failed to show such an effect. In a second experiment, resemblance of the playing partner to a familiar (famous) person had no effect on either trusting or betrayals of trust.

  14. 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.

  15. Non-steroidal anti-inflammatory drugs versus corticosteroids for controlling inflammation after uncomplicated cataract surgery.

    PubMed

    Juthani, Viral V; Clearfield, Elizabeth; Chuck, Roy S

    2017-07-03

    Cataract is a leading cause of blindness worldwide. Cataract surgery is commonly performed but can result in postoperative inflammation of the eye. Inadequately controlled inflammation increases the risk of complications. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are used to prevent and reduce inflammation following cataract surgery, but these two drug classes work by different mechanisms. Corticosteroids are effective, but NSAIDs may provide an additional benefit to reduce inflammation when given in combination with corticosteroids. A comparison of NSAIDs to corticosteroids alone or combination therapy with these two anti-inflammatory agents will help to determine the role of NSAIDs in controlling inflammation after routine cataract surgery. To evaluate the comparative effectiveness of topical NSAIDs (alone or in combination with topical corticosteroids) versus topical corticosteroids alone in controlling intraocular inflammation after uncomplicated phacoemulsification. To assess postoperative best-corrected visual acuity (BCVA), patient-reported discomfort, symptoms, or complications (such as elevation of IOP), and cost-effectiveness with the use of postoperative NSAIDs or corticosteroids. To identify studies relevant to this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2016, Issue 12), MEDLINE Ovid (1946 to December 2016), Embase Ovid (1947 to 16 December 2016), PubMed (1948 to December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 16 December 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com; last searched 17 June 2013), ClinicalTrials.gov (www.clinicaltrials.gov; searched December 2016), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en; searched December 2016). We included randomized controlled trials (RCTs) in which

  16. Systemic inflammation alters the inflammatory response in experimental lipopolysaccharide-induced meningitis

    PubMed Central

    O'Reilly, T; Østergaard, C; Vaxelaire, J; Zak, O

    2007-01-01

    Experiments to evaluate the effect of the level and duration of endotoxaemia on the meningeal inflammatory response were performed in order to determine if systemic inflammation alters meningitis. Rabbits received either saline or Escherichia coli O111:B4 lipopolysacharide (LPS) intravenously at various doses (1, 3 or 10 µg) and times (−8, −2 or 0 h) before an intracisternal injection of 20 ng LPS. An intracisternal LPS injection together with saline intravenously produced a peak cerebrospinal fluid (CSF) tumour necrosis factor (TNF) level (95 ± 26 ng/ml) at 2 h and peak leucocyte level (5413 ± 764 cells/µl) at 4 h post-injection. Blood leucocytes were slightly elevated (12 000 ± 500/µl at 0 h; 16 900 ± 280/µl at 8 h) but plasma TNF was always undetectable (< 0·05 ng/ml). Conversely, intravenous injection of 3 or 10 µg LPS 2 h prior to intracisternal LPS injection impaired pleocytosis (peak < 220 cells/µl) and delayed (∼4 h) and reduced peak CSF TNF levels (3 µg LPS 5·0 ± 1·2 ng/ml; 10 µg LPS 6·9 ± 1·9; P < 0·05). Intravenous administration of 1 µg LPS was less inhibitory to CSF inflammation, but delayed onset (peak 1100 ± 60 leucocytes/µl CSF at 8 h; 6·3 ± 0·3 ng TNF/ml CSF at 4 h; both P < 0·05). Neutropenia nadirs were dependent on LPS dose (1 µg, 4500 ± 1700; 3 µg, 1900 ± 60; 10 µg, 1100 ± 100 all at 4 h post-intravenous dose). Peak plasma TNF levels were not dose-dependent (> 8 ng/ml), but plasma TNF was always detectable (> 0·2 ng/ml at 10 h post-intravenous dose). Intravenous LPS administration at 0 h also blocked pleocytosis, but the inhibitory effect was lost when administration at −8 h. In conclusion, the degree and duration of endotoxaemia affect the meningeal inflammatory response to LPS in experimental meningitis. PMID:17177970

  17. Gene Delivery of a Viral Anti-Inflammatory Protein to Combat Ocular Inflammation

    PubMed Central

    Ildefonso, Cristhian J.; Jaime, Henrique; Rahman, Masmudur M.; Li, Qiuhong; Boye, Shannon E.; Hauswirth, William W.; Lucas, Alexandra R.; McFadden, Grant

    2015-01-01

    Abstract Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with the proinflammatory signaling pathways involving both the NLRP3 inflammasome and NF-κB. We have developed and characterized an adeno-associated viral (AAV) vector that delivers a secretable and cell-penetrating form of the M013 protein (TatM013). The expressed TatM013 protein was secreted and blocked the endotoxin-induced secretion of interleukin (IL)-1β in monocyte-derived cells and the reactive aldehyde-induced secretion of IL-1β in retinal pigment epithelium cells. The local anti-inflammatory effects of AAV-delivered TatM013 were evaluated in an endotoxin-induced uveitis (EIU) mouse model after intravitreal injection of mice with an AAV2-based vector carrying either TatM013 fused to a secreted green fluorescent protein (GFP) tag (sGFP-TatM013) or GFP. Expression of the sGFP-TatM013 transgene was demonstrated by fluorescence funduscopy in living mice. In EIU, the number of infiltrating cells and the concentration of IL-1β in the vitreous body were significantly lower in the eyes injected with AAV-sGFP-TatM013 compared with the eyes injected with control AAV-GFP. These results suggest that a virus-derived inhibitor of the innate immune response, when delivered via AAV, could be a generalized therapy for various inflammatory diseases of the eye. PMID:25420215

  18. Gene delivery of a viral anti-inflammatory protein to combat ocular inflammation.

    PubMed

    Ildefonso, Cristhian J; Jaime, Henrique; Rahman, Masmudur M; Li, Qiuhong; Boye, Shannon E; Hauswirth, William W; Lucas, Alexandra R; McFadden, Grant; Lewin, Alfred S

    2015-01-01

    Inflammation of the retina is a contributing factor in ocular diseases such as uveitis, diabetic retinopathy, and age-related macular degeneration (AMD). The M013 immunomodulatory protein from myxoma virus has been shown to interfere with the proinflammatory signaling pathways involving both the NLRP3 inflammasome and NF-κB. We have developed and characterized an adeno-associated viral (AAV) vector that delivers a secretable and cell-penetrating form of the M013 protein (TatM013). The expressed TatM013 protein was secreted and blocked the endotoxin-induced secretion of interleukin (IL)-1β in monocyte-derived cells and the reactive aldehyde-induced secretion of IL-1β in retinal pigment epithelium cells. The local anti-inflammatory effects of AAV-delivered TatM013 were evaluated in an endotoxin-induced uveitis (EIU) mouse model after intravitreal injection of mice with an AAV2-based vector carrying either TatM013 fused to a secreted green fluorescent protein (GFP) tag (sGFP-TatM013) or GFP. Expression of the sGFP-TatM013 transgene was demonstrated by fluorescence funduscopy in living mice. In EIU, the number of infiltrating cells and the concentration of IL-1β in the vitreous body were significantly lower in the eyes injected with AAV-sGFP-TatM013 compared with the eyes injected with control AAV-GFP. These results suggest that a virus-derived inhibitor of the innate immune response, when delivered via AAV, could be a generalized therapy for various inflammatory diseases of the eye.

  19. Analgesic and anti-inflammatory actions of robenacoxib in acute joint inflammation in dog.

    PubMed

    Schmid, V B; Spreng, D E; Seewald, W; Jung, M; Lees, P; King, J N

    2010-04-01

    The objectives of this study were to establish dose-response and blood concentration-response relationships for robenacoxib, a novel nonsteroidal anti-inflammatory drug with selectivity for inhibition of the cyclooxygenase (COX)-2 isoenzyme, in a canine model of synovitis. Acute synovitis of the stifle joint was induced by intra-articular injection of sodium urate crystals. Robenacoxib (0.25, 0.5, 1.0, 2.0 and 4.0 mg/kg), placebo and meloxicam (0.2 mg/kg) were administered subcutaneously (s.c.) 3 h after the urate crystals. Pharmacodynamic endpoints included data from forceplate analyses, clinical orthopaedic examinations and time course of inhibition of COX-1 and COX-2 in ex vivo whole blood assays. Blood was collected for pharmacokinetics. Robenacoxib produced dose-related improvement in weight-bearing, pain and swelling as assessed objectively by forceplate analysis (estimated ED(50) was 1.23 mg/kg for z peak force) and subjectively by clinical orthopaedic assessments. The analgesic and anti-inflammatory effects of robenacoxib were significantly superior to placebo (0.25-4 mg/kg robenacoxib) and were non-inferior to meloxicam (0.5-4 mg/kg robenacoxib). All dosages of robenacoxib produced significant dose-related inhibition of COX-2 (estimated ED(50) was 0.52 mg/kg) but no inhibition of COX-1. At a dosage of 1-2 mg/kg administered s.c., robenacoxib should be at least as effective as 0.2 mg/kg of meloxicam in suppressing acute joint pain and inflammation in dogs.

  20. Dehydroepiandrosterone (DHEA) restrains intestinal inflammation by rendering leukocytes hyporesponsive and balancing colitogenic inflammatory responses.

    PubMed

    Alves, Vanessa Beatriz Freitas; Basso, Paulo José; Nardini, Viviani; Silva, Angélica; Chica, Javier Emílio Lazo; Cardoso, Cristina Ribeiro de Barros

    2016-09-01

    Dehydroepiandrosterone (DHEA) is a hormone that plays an important role in the modulation of inflammatory responses. However, the precise mechanisms that link the actions of this androgen with protection or susceptibility to inflammatory bowel diseases (IBD) remain uknown. Here we showed that low dose DHEA inhibited proliferation of spleen cells and IFN-у production. The hormone was not toxic to myeloid lineage cells, although it caused necrosis of spleen cells at the intermediate and highest doses in vitro (50 and 100μM). The treatment of C57BL/6 mice with DHEA during colitis induction by dextran sodium sulfate (DSS) led to a reduction in weight loss and clinical signs of disease. There were decreased peripheral blood monocytes on day 6 of DSS exposure and treatment, besides increase in circulating neutrophils in the tissue repair phase. DHEA also led to reduced lamina propria cellularity and restoration of normal colon length. These results were accompanied by decreased expression of IL-6 and TGF-β mRNA, while IL-13 was augmented in the colon on day 6, which was probably related to attenuation of inflammation. There was retention of CD4(+) cells in the spleen after use of DHEA, along with augmented frequency of CD4(+)IL-4(+) cells, decreased CD4(+)IFN-ɣ(+) in spleen and constrained CD4(+)IL-17(+) population in the mesenteric lymph nodes. Moreover, splenocytes of mice treated with DHEA became hyporesponsive, as observed by reduced proliferation after re-stimulation ex-vivo. In conclusion, DHEA modifyies leukocyte activity and balances the exacerbated immune responses which drive local and systemic damages in IBD. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. IMMUNOLOGIC AND GENETIC MARKERS IN PATIENTS WITH IDIOPATHIC OCULAR INFLAMMATION AND A FAMILY HISTORY OF INFLAMMATORY BOWEL DISEASE

    PubMed Central

    Abbasian, Javaneh; Martin, Tammy M.; Patel, Sarju; Tessler, Howard H; Goldstein, Debra A

    2014-01-01

    PURPOSE: To evaluate the prevalence of immunologic and genetic markers in patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease. DESIGN: Prospective, matched case-control study. METHODS: Patients with a diagnosis of idiopathic ocular inflammation and family history of inflammatory bowel disease (IBD) who did not have IBD themselves were identified and matched to control patients with idiopathic ocular inflammation without a personal or family history of IBD. Serum was evaluated for immunologic markers using Prometheus IBD 7 Serology®. Genomic DNA was analyzed for single nucleotide polymorphisms (SNP) of the NOD2 gene associated with Crohn’s disease. RESULTS: Fifteen patients with idiopathic ocular inflammation and family history of inflammatory bowel disease were matched to fifteen control patients based on age, gender, and race. 8/15 (53%) patients with a family history of IBD had elevated p-ANCA antibody levels compared to 3/15 (20%) of controls (one sided P=0.04) with a matched analysis OR of 6.0 [one-sided P=0.06]. 4/15 (27%) patients with family history of IBD tested positive for immunologic markers predicting ulcerative colitis, while no control patients tested positive [one-sided P=0.06]. Carrier rates of NOD2 SNPs did not differ significantly between the test and control groups. CONCLUSIONS: One quarter of patients with idiopathic ocular inflammation and a family history of inflammatory bowel disease had immunologic markers predicting IBD, and one half had elevated p-ANCA levels. IBD serology may be useful in the evaluation of selected patients with unexplained uveitis. PMID:22464367

  2. Evolutionary medicine and bone loss in chronic inflammatory diseases – a theory of inflammation-related osteopenia

    PubMed Central

    Straub, Rainer H.; Cutolo, Maurizio; Pacifici, Roberto

    2015-01-01

    Objective Bone loss is typical in chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, ankylosing spondylitis, systemic lupus erythematosus, multiple sclerosis, inflammatory bowel diseases, pemphigus vulgaris, and others. It is also typical in transplantation-related inflammation and during the process of aging. While we recognized that bone loss is tightly linked to immune system activation or inflammaging in the form of acute, chronic active, or chronic smoldering inflammation, bone loss is typically discussed to be an “accident of inflammation”. Methods Extensive literature search in PubMed central. Results Using elements of evolutionary medicine, energy regulation, and neuroendocrine regulation of homeostasis and immune function, we work out that bone waste is an adaptive, evolutionarily positively selected program that is absolutely necessary during acute inflammation. However, when acute inflammation enters a chronic state due to the inability to terminate inflammation (e.g., in autoimmunity or in continuous immunity against microbes), the acute program of bone loss is a misguided adaptive program. Conclusions The article highlights the complexity of interwoven pathways of osteopenia. PMID:26044543

  3. Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease

    PubMed Central

    Scaldaferri, Franco; Sans, Miquel; Vetrano, Stefania; Graziani, Cristina; De Cristofaro, Raimondo; Gerlitz, Bruce; Repici, Alessandro; Arena, Vincenzo; Malesci, Alberto; Panes, Julian; Grinnell, Brian W.; Danese, Silvio

    2007-01-01

    Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and convert protein C (PC) into its activated form, which is a potent anticoagulant and antiinflammatory molecule. Here we provide evidence that in Crohn disease (CD) and ulcerative colitis (UC), the 2 major forms of inflammatory bowel disease (IBD), there was loss of expression of endothelial EPCR and TM, which in turns caused impairment of PC activation by the inflamed mucosal microvasculature. In isolated human intestinal endothelial cells, administration of recombinant activated PC had a potent antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell adhesion molecule expression and chemokine production as well as inhibited leukocyte adhesion. In vivo, administration of activated PC was therapeutically effective in ameliorating experimental colitis as evidenced by reduced weight loss, disease activity index, and histological colitis scores as well as inhibited leukocyte adhesion to the inflamed intestinal vessels. The results suggest that the PC pathway represents a new system crucially involved in governing intestinal homeostasis mediated by the mucosal microvasculature. Restoring the PC pathway may represent a new therapeutic approach to suppress intestinal inflammation in IBD. PMID:17557119

  4. Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs.

    PubMed

    Kyriakopoulos, Anthony M; Nagl, Markus; Baliou, Stella; Zoumpourlis, Vasilleios

    2017-01-01

    Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided.

  5. Alleviating Promotion of Inflammation and Cancer Induced by Nonsteroidal Anti-Inflammatory Drugs

    PubMed Central

    Nagl, Markus; Baliou, Stella; Zoumpourlis, Vasilleios

    2017-01-01

    Clinical Relevance Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) including aspirin are of intensive use nowadays. These drugs exert their activity via the metabolism of arachidonic acid (AA) by cyclooxygenase inhibition. Though beneficial for health in some instances, both unspecific and specific cyclooxygenase inhibitor activity interfere with AA metabolism producing also proinflammatory lipids that may promote cancer. Materials and Methods This review is based on available literature on clinical uses, biochemical investigations, molecular medicine, pharmacology, toxicity, and epidemiology-clinical studies on NSAIDs and other drugs that may be used accordingly, which was collected from electronic (SciFinder, Medline, Science Direct, and ACS among others) and library searches of books and journals. Results Relevant literature supports the notion that NDSAID use may also promote proinflammatory biochemical events that are also related to precancerous predisposition. Several agents are proposed that may be employed in immediate future to supplement and optimize treatment with NSAIDs. In this way serious side effects arising from promotion of inflammation and cancer, especially in chronic NSAID users and high risk groups of patients, could be avoided. PMID:28573063

  6. Substance P and the regulation of inflammation in infections and inflammatory bowel disease.

    PubMed

    Weinstock, J V

    2015-02-01

    Substance P (SP) and its natural analogue hemokinin-1 (HK1) are produced by lymphocytes and macrophages, and at times B cells. These peptides are an important component of the immune response during several infections and in inflammatory bowel disease (IBD). The synthesis of SP and HK1 in leucocytes is subject to immune regulation. IL12 and IL23 stimulate T cells and macrophages to make SP respectively. The cytokines driving HK1 production are not presently defined. These peptides act through a shared receptor called neurokinin-1. T cells, macrophages and probably other immune cell types can express this receptor. Several cytokines IL12, IL18 and TNFα as well as T-cell antigen receptor activation induce neurokinin-1 receptor expression on T cells, while IL10 blocks receptor display. TGFβ delays internalization of the SP/neurokine-1R complex on T cells resulting in stronger receptor signalling. One of the functions of SP and neurokinin-1 receptor is to enhance T cell IFNγ and IL17 production, amplifying the proinflammatory response. Thus, SP and HK1 have overlapping functions and are part of a sophisticated immune regulatory circuit aimed at amplifying inflammation at mucosal surfaces and in other regions of the body as shown in animal models of infection and IBD. © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  7. The anti-inflammatory effect of alloferon on UVB-induced skin inflammation through the down-regulation of pro-inflammatory cytokines.

    PubMed

    Kim, Yejin; Lee, Seung Koo; Bae, Seyeon; Kim, Hyemin; Park, Yunseong; Chu, Nag Kyun; Kim, Stephanie G; Kim, Hang-Rae; Hwang, Young-Il; Kang, Jae Seung; Lee, Wang Jae

    2013-01-01

    UVB irradiation can induce biological changes in the skin, modulate immune responses and activate inflammatory reactions leading to skin damage. Alloferon, which is isolated from the blood of an experimentally infected insect, the blow fly Calliphora vicina, is known for its anti-viral and anti-tumor activities in mice model. However, the effect of alloferon against UVB irradiation and its specific mechanism are still unknown. In this study, we investigated the effect of alloferon on UVB-induced cutaneous inflammation in a human keratinocyte cell line, HaCaT. RPA and ELISA data showed that alloferon decreased the production of UVB-induced pro-inflammatory cytokines, such as IL-1α, IL-1β, IL-6 and IL-18, both on the mRNA and protein level. Western blot analysis was done to determine if alloferon regulates the MAPK signaling pathway since the MAPK signaling pathway is activated by numerous inflammatory mediators and environmental stresses including UVB irradiation. Alloferon inhibited the activation of p38 mitogen-activated protein kinase (MAPK) induced by UVB irradiation. Furthermore, the topical application of alloferon on the UVB exposed skin of hairless mice showed that alloferon treatment significantly inhibited an increase in epithelial thickness in chronic UVB-irradiated mouse skin. These findings suggest that alloferon has significant anti-inflammatory effects not only on UVB-induced inflammation in the human keratinocyte cell line, HaCaT, but also on mouse skin.

  8. Anti-inflammatory effects of formoterol and ipratropium bromide against acute cadmium-induced pulmonary inflammation in rats.

    PubMed

    Zhang, Wenhui; Fievez, Laurence; Cheu, Esteban; Bureau, Fabrice; Rong, Weifang; Zhang, Fan; Zhang, Yong; Advenier, Charles; Gustin, Pascal

    2010-02-25

    In this study, the anti-inflammatory properties of formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of acute pulmonary inflammation induced by cadmium inhalation. Airway resistance and inflammatory responses, including matrix metalloproteinease-2 (MMP-2) and matrix metalloproteinease-9 (MMP-9) activities, were evaluated. Compared to values obtained in rats exposed to cadmium, pretreatment by bronchodilators administered alone significantly prevented the cadmium-induced increase of airway resistance. Formoterol elicited a significant decrease in total cell number, neutrophil and macrophage counts in bronchoalveolar lavage fluid, whereas ipratropium bromide reduced neutrophil numbers. The two compounds administered alone significantly attenuated the lung lesions associated with parenchyma inflammatory cell influx and congestion observed in the cadmium group. The increased MMP-9 activity was significantly attenuated. Although only formoterol induced a decrease protein concentration in bronchoalveolar lavage fluid, both compounds inhibited the pulmonary edema by reducing wet-to-dry weight ratio which returned to values similar to those recorded in the sham group. All the effects of formoterol on the cadmium-induced inflammatory responses were reversed by propranolol. Similar anti-inflammatory effects were obtained in rats pretreated with ilomastat which showed a significant reduction on inflammatory cell infiltration and MMP-9 activity in bronchoalveolar lavage fluid. Neither synergistic nor additive effects were obtained when the two bronchodilators were administered in combination. In conclusion, formoterol and ipratropium bromide partially protect the lungs against the inflammation by reducing neutrophilic infiltration. This protective effect is associated with reduced MMP-9 activity known to play an important pro-inflammatory role in acute inflammatory process.

  9. Tle1 tumor suppressor negatively regulates inflammation in vivo and modulates NF-κB inflammatory pathway

    PubMed Central

    Ramasamy, Selvi; Saez, Borja; Mukhopadhyay, Subhankar; Ding, Daching; Ahmed, Alwiya M.; Chen, Xi; Pucci, Ferdinando; Yamin, Rae’e; Wang, Jianfeng; Pittet, Mikael J.; Kelleher, Cassandra M.; Scadden, David T.; Sweetser, David A.

    2016-01-01

    Tle1 (transducin-like enhancer of split 1) is a corepressor that interacts with a variety of DNA-binding transcription factors and has been implicated in many cellular functions; however, physiological studies are limited. Tle1-deficient (Tle1Δ/Δ) mice, although grossly normal at birth, exhibit skin defects, lung hypoplasia, severe runting, poor body condition, and early mortality. Tle1Δ/Δ mice display a chronic inflammatory phenotype with increased expression of inflammatory cytokines and chemokines in the skin, lung, and intestine and increased circulatory IL-6 and G-CSF, along with a hematopoietic shift toward granulocyte macrophage progenitor and myeloid cells. Tle1Δ/Δ macrophages produce increased inflammatory cytokines in response to Toll-like receptor (TLR) agonists and lipopolysaccharides (LPS), and Tle1Δ/Δ mice display an enhanced inflammatory response to ear skin 12-O-tetradecanoylphorbol-13-acetate treatment. Loss of Tle1 not only results in increased phosphorylation and activation of proinflammatory NF-κB but also results in decreased Hes1 (hairy and enhancer of split-1), a negative regulator of inflammation in macrophages. Furthermore, Tle1Δ/Δ mice exhibit accelerated growth of B6-F10 melanoma xenografts. Our work provides the first in vivo evidence, to our knowledge, that TLE1 is a major counterregulator of inflammation with potential roles in a variety of inflammatory diseases and in cancer progression. PMID:26831087

  10. Fetal Inflammatory Response in Women with Proteomic Biomarkers Characteristic of Intra-Amniotic Inflammation and Preterm Birth

    PubMed Central

    Buhimschi, Catalin S.; Dulay, Antonette T.; Abdel-Razeq, Sonya; Zhao, Guomao; Lee, Sarah; Hodgson, Eric J.; Bhandari, Vineet; Buhimschi, Irina A.

    2013-01-01

    Objective To determine the relationship between presence of amniotic fluid (AF) biomarkers characteristic of inflammation (defensins 2 and 1, calgranulins C and A) and fetal inflammatory status at birth. Design Prospective observational cohort. Setting Tertiary referral University hospital Population 132 consecutive mothers (gestational age, median [interquartile range]: 29.6 [24.1-33.6] weeks), who had a clinically indicated amniocentesis to rule-out infection and their newborns. Methods Intra-amniotic inflammation was diagnosed by mass spectrometry SELDI-TOF. The AF proteomic fingerprint [Mass Restricted (MR) score] ranges from 0-4 (none to all biomarkers present). The intensity of intra-amniotic inflammation was graded based on the number of proteomic biomarkers: MR score 0: “no” inflammation; MR score 1-2: “minimal” inflammation; MR score 3-4: “severe” inflammation. At birth, cord blood was obtained for all cases. Severity of histological chorioamnionitis (HCA) and early onset neonatal sepsis (EONS) was based on established histological and hematological criteria. Interleukin-6 (IL-6) levels were measured by sensitive immunoassays. The cord blood-to-AF IL-6 ratio was used as an indicator of the differential inflammatory response in the fetal versus the AF compartment. Main Outcome Measures to relate proteomic biomarkers of intra-amniotic infection to cord blood IL-6 and to use the latter as the primary marker of fetal inflammatory response. Results Women with intra-amniotic inflammation delivered at an earlier gestational age (ANOVA, P<0.001) and had higher AF IL-6 levels (P<0.001). At birth, neonates of women with “severe” intra-amniotic inflammation had higher cord blood IL-6 levels (P=0.002) and a higher frequency of EONS (P=0.002). EONS was characterized by significantly elevated cord blood IL-6 levels (P<0.001). Out of the 39 neonates delivered by mothers with “minimal” intra-amniotic inflammation, 15 (39%) had umbilical cord blood IL-6

  11. Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis: an inflammatory kidney model

    PubMed Central

    Truong, Luan D.; Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Inflammation is regulated by endogenous mechanisms, including anti-inflammatory cytokines, adenosine, and the nicotinic acetylcholine receptor α7 subunit (α7nAChR). We investigated the role of α7nAChR in protection against the progression of tissue injury in a model of severe, macrophage-mediated, cytokine-dependent anti-glomerular basement membrane (GBM) glomerulonephritis (GN), in α7nAChR-deficient (α7−/−) mice . At d 7 after the injection of anti-GBM antibody, kidneys from α7−/− mice displayed severe glomeruli (P < 0.0001) and tubulointerstitial lesions (P < 0.001) compared to kidneys from WT mice. An important finding was the presence of severe glomerulosclerosis in α7−/− mice in this early phase of the disease. Kidneys of α7−/− mice showed greater accumulation of inflammatory cells and higher expression of chemokines and cytokines than did those of WT mice. In addition, in α7−/− fibrotic kidneys, the expression of fibrin, collagen, TGF-β, and tissue inhibitor of metalloproteinase (TIMP)-2 increased, and the expression of TIMP3 declined. The increase in counterregulatory responses to inflammation in α7−/− nephritic kidneys did not compensate for the lack of α7nAChR. These findings indicate that α7nAChR plays a key role in regulating the inflammatory response in anti-GBM GN and that disruption of the endogenous protective α7nAChR amplifies inflammation to accelerate kidney damage and fibrosis.—Truong, L. D., Trostel. J., Garcia, G. E. Absence of nicotinic acetylcholine receptor α7 subunit amplifies inflammation and accelerates onset of fibrosis: an inflammatory kidney model. PMID:25985801

  12. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines.

    PubMed

    Liu, Yun; Chen, Lulu; Zhi, Chunchun; Shen, Ming; Sun, Weiwei; Miao, Dengshun; Yuan, Xiaoqin

    2016-01-01

    Epidemiological studies showed that 1,25-Dihydroxyvitamin D[1,25(OH)2D3] insufficiency appears to be associated with aging and colon cancer while underlying biological mechanisms remain largely unknown. Inflammatory bowel disease is one of the risk factors for colon cancer. In this study, we investigated whether 1,25(OH)2D3 deficiency has an impact on the colon of 25-hydroxyvitamin D 1α-hydroxylase knockout [Cyp27b1(-/-)] mice fed on a rescue diet (high calcium, phosphate, and lactose) from weaning to 10 months of age. We found that 1,25(OH)2D3 deficient mice displayed significant colon inflammation phenotypes including shortened colon length, thinned and disordered mucosal structure, and inflammatory cell infiltration. DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were also increased significantly in the colon of Cyp27b1(-/-)mice. Furthermore, the levels of ROS in the colon were increased significantly, whereas the expression levels of antioxidative genes were down-regulated dramatically in the colon of Cyp27b1(-/-)mice. Taken together, our results demonstrated that 1,25(OH)2D3 deficiency could induce colon inflammation, which may result from increased oxidative stress and DNA damage, subsequently, induced cell senescence and overproduction of senescence-associated secretory factors. Therefore, our findings suggest that 1,25(OH)2D3 may play an important role in preventing the development and progression of colon inflammation and colon cancer.

  13. Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation.

    PubMed

    Igbe, Ighodaro; Ching, Fidelis P; Eromon, Aigbe

    2010-01-01

    The anti-inflammatory effect of the aqueous fruit pulp extract of Hunteria umbellata K. Schum (Apocynaceae) was evaluated using the carrageenan- and dextran-induced rat paw edema, xylene-induced ear edema and formalin-induced arthritis inflammation tests. Oral administration of the extract produced significant (p < 0.05) antiedematogenic effect with a dose of 500 mg/kg throughout the period of the experiment in the dextran induced paw edema and at the 3 h in the carrageenan model. The extract (250 and 500 mg/kg) exhibited a dose-related and significant (p < 0.01) inhibition of xylene induced ear edema and the effect was similar to that produced by dexamethasone (1 mg/kg). In the chronic inflammation (formalin induced arthritis) the extract did not show any significant anti-inflammatory activity. Oral acute toxicity assays did not show any mortality at 15 g/kg of the plant extract. The results indicate that the aqueous extract of H. umbellata possesses acute inflammatory activity which may be mediated by either inhibition or by blocking the release of prostaglandins and histamine, thus supporting the usage of the plant in traditional medicine treatment of inflammation.

  14. Role of the endothelial-derived endogenous anti-inflammatory factor Del-1 in inflammation-mediated adrenal gland dysfunction.

    PubMed

    Kanczkowski, Waldemar; Chatzigeorgiou, Antonios; Grossklaus, Sylvia; Sprott, David; Bornstein, Stefan R; Chavakis, Triantafyllos

    2013-03-01

    Inflammation in the course of systemic inflammatory response syndrome (SIRS) or sepsis often results in dysregulation of the hypothalamic-pituitary-adrenal axis; however, the underlying mechanisms are not well understood. The adrenal gland is highly vascularized; thus, we hypothesized that endothelial dysfunction may actively participate in inflammation-related adrenal insufficiency. To address this hypothesis, we used the properties of developmental endothelial locus-1 (Del-1), which is an endothelial-derived anti-inflammatory factor that antagonizes integrin-dependent leukocyte adhesion. Here we identified that Del-1 is expressed in the adrenal gland and that its expression was down-regulated upon SIRS induction by systemic lipopolysaccharide administration. Furthermore, we observed increased leukocyte accumulation, inflammation, and higher apoptosis in the adrenal glands of Del-1-deficient mice as compared with wild-type mice. Strikingly, Del-1 deficiency was also associated with reduced corticosterone and ACTH levels 24 hours after lipopolysaccharide administration. Together, these data suggest that Del-1 may act as a gatekeeper of adrenal gland inflammation and may regulate the integrity of the hypothalamic-pituitary-adrenal axis stress response, thereby modulating adrenal (dys)function in the course of SIRS.

  15. Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1α to Reduce Acute Lung Inflammation and Injury in Mice

    PubMed Central

    Quintero, Pablo A.; Knolle, Martin D.; Cala, Luisa F.; Zhuang, Yuehong; Owen, Caroline A.

    2010-01-01

    To determine the role of matrix metalloproteinase-8 (MMP-8) in acute lung injury (ALI), we delivered LPS or bleomycin by the intratracheal route to MMP-8−/− mice versus WT mice or subjected the mice to hyperoxia (95% O2) and measured lung inflammation and injury at intervals. MMP-8−/− mice with ALI had greater increases in lung PMN and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8−/− mice had more macrophage inflammatory protein-1α (MIP-1α) than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1α−/− mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1α promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1α in MMP-8−/− mice abrogated the increased lung inflammation and injury and mortality in MMP-8−/− mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1α in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1α-degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1α. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI. PMID:20042585

  16. Lutein derived fragments exhibit higher antioxidant and anti-inflammatory properties than lutein in lipopolysaccharide induced inflammation in rats.

    PubMed

    Nidhi, Bhatiwada; Sharavana, Gurunathan; Ramaprasad, Talahalli R; Vallikannan, Baskaran

    2015-02-01

    In the present study, we appraise the anti-inflammatory efficacy of lutein oxidative degradation derivatives mediated through UV-irradiation over lutein in counteracting the inflammation induced by lipopolysaccharide (LPS) in rats (n = 5 per group). UV-irradiated lutein fragments were identified as anhydrolutein (B, C40H54O), 2,6,6-trimethylcyclohexa-1,4-dienylium (M1, C9H13), (2E,4E,6E,8E)-9-(4-hydroxy-2,6,6-trimethylcyclohex-1-1en-1-yl)-3,7-dimethylnona-2,4,6,8-tetraen-1-ylium (M2, C20H29O), 4-[(1E,3E,5E,7E)-3,7,-dimethyldeca-1,3,5,7-tetraen-1-yl]-3,5,5-methylcyclohex-3-en-1-ol (M3, C21H30O) and zeaxanthin (M4, C40H56O) and its isomers as 13'-Z zeaxanthin, 13'-Z lutein, all-trans zeaxanthin, and 9-Z lutein. Induction of inflammation by LPS significantly increased the production of nitrites (3.3 fold in the serum and 2.6 fold in the liver), prostaglandin E2 (26 fold in the serum), and pro-inflammatory cytokines like tumor necrosis factor-α (6.6 fold in the serum), and interleukin-6 (4.8 fold in the serum). Oxidative derivatives of lutein, especially M1, M2 and M3, ameliorated acute inflammation in rats by inhibiting the production of nitrites, malondialdehyde (MDA), PGE2, TNF-α, and IL-6 cytokines more efficiently than lutein in rats. The anti-inflammatory mechanism of derivatives might be related to the decrease of inflammatory cytokines and the increase of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione S transferase, glutathione reductase), which would result in the reduction of iNOS, COX-2 and MDA and subsequently inflammatory responses.

  17. The sickle cell mouse lung: pro-inflammatory and primed for allergic inflammation

    PubMed Central

    Andemariam, Biree; Adami, Alexander J.; McNamara, Jeffrey T.; Secor, Eric R.; Guernsey, Linda A.; Thrall, Roger S.

    2015-01-01

    Co-morbid asthma in sickle cell disease (SCD) confers higher rates of vaso-occlusive pain and mortality, yet the physiological link between these two distinct diseases remains puzzling. We utilized a mouse model of SCD to study pulmonary immunology and physiology before and after the induction of allergic airway disease (AAD). SCD mice were sensitized with ovalbumin (OVA) and aluminum hydroxide by the intraperitoneal (IP) route followed by daily, nose-only OVA-aerosol challenge to induce AAD. The lungs of naive SCD mice showed signs of inflammatory and immune processes: (1) histologic and cytochemical evidence of airway inflammation as compared to naïve wildtype mice; (2) bronchoalveolar lavage fluid (BAL) contained increased total lymphocytes, %CD8+ T cells, G-CSF, IL-5, IL-7, and CXCL1, and (3) lung tissue and hilar lymph node (HLN) had increased CD4+, CD8+, and regulatory T cells (Tregs). Further, SCD mice at AAD demonstrated significant changes compared to the naïve state: (1) BAL with increased %CD4+ T cells and Tregs, lower %CD8+ T cells, and decreased IFNγ, CXCL10, CCL2, and IL-17, (2) serum with increased OVA-specific IgE, IL-6, and IL-13, and decreased IL-1α and CXCL10, (3) no increase in Tregs in the lung tissue or HLN, and (4) hypo-responsiveness to methacholine challenge. In conclusion, SCD mice have an altered immunologic pulmonary milieu and physiologic responsiveness. These findings suggest that the clinical phenotype of AAD in SCD mice differs from that of wildtype mice and suggests that individuals with SCD may also have a unique, divergent phenotype perhaps amenable to a different therapeutic approach. PMID:25843670

  18. Glucocorticoids limit acute lung inflammation in concert with inflammatory stimuli by induction of SphK1

    PubMed Central

    Vettorazzi, Sabine; Bode, Constantin; Dejager, Lien; Frappart, Lucien; Shelest, Ekaterina; Klaßen, Carina; Tasdogan, Alpaslan; Reichardt, Holger M.; Libert, Claude; Schneider, Marion; Weih, Falk; Henriette Uhlenhaut, N.; David, Jean-Pierre; Gräler, Markus; Kleiman, Anna; Tuckermann, Jan P.

    2015-01-01

    Acute lung injury (ALI) is a severe inflammatory disease for which no specific treatment exists. As glucocorticoids have potent immunosuppressive effects, their application in ALI is currently being tested in clinical trials. However, the benefits of this type of regimen remain unclear. Here we identify a mechanism of glucocorticoid action that challenges the long-standing dogma of cytokine repression by the glucocorticoid receptor. Contrarily, synergistic gene induction of sphingosine kinase 1 (SphK1) by glucocorticoids and pro-inflammatory stimuli via the glucocorticoid receptor in macrophages increases circulating sphingosine 1-phosphate levels, which proves essential for the inhibition of inflammation. Chemical or genetic inhibition of SphK1 abrogates the therapeutic effects of glucocorticoids. Inflammatory p38 MAPK- and mitogen- and stress-activated protein kinase 1 (MSK1)-dependent pathways cooperate with glucocorticoids to upregulate SphK1 expression. Our findings support a critical role for SphK1 induction in the suppression of lung inflammation by glucocorticoids, and therefore provide rationales for effective anti-inflammatory therapies. PMID:26183376

  19. Arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan, inhibits type I-IV allergic inflammation and pro-inflammatory enzymes.

    PubMed

    Lee, Ji Yun; Kim, Chang Jong

    2010-06-01

    We previously reported that arctigenin, a phenylpropanoid dibenzylbutyrolactone lignan isolated from Forsythia koreana, exhibits anti-inflammatory, antioxidant, and analgesic effects in animal models. In addition, arctigenin inhibited eosinophil peroxidase and activated myeloperoxidase in inflamed tissues. In this study, we tested the effects of arctigenin on type I-IV allergic inflammation and pro-inflammatory enzymes in vitro and in vivo. Arctigenin significantly inhibited the heterologous passive cutaneous anaphylaxis induced by ovalbumin in mice at 15 mg/kg, p.o., and compound 48/80-induced histamine release from rat peritoneal mast cells at 10 microM. Arctigenin (15 mg/kg, p.o.) significantly inhibited reversed cutaneous anaphylaxis. Further, arctigenin (15 mg/kg, p.o.) significantly inhibited the Arthus reaction to sheep's red blood cells, decreasing the hemolysis titer, the hemagglutination titer, and the plaque-forming cell number for SRBCs. In addition, arctigenin significantly inhibited delayed type hypersensitivity at 15 mg/kg, p.o. and the formation of rosette-forming cells at 45 mg/kg, p.o. Contact dermatitis induced by picrylchloride and dinitrofluorobenzene was significantly (p < 0.05) inhibited by surface treatment with arctigenin (0.3 mg/ear). Furthermore, arctigenin dose-dependently inhibited pro-inflammatory enzymes, such as cyclooxygenase-1 and 2, 5-lipoxygenase, phospholipase A2, and phosphodiesterase. Our results show that arctigenin significantly inhibited B- and T-cell mediated allergic inflammation as well as pro-inflammatory enzymes.

  20. The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease.

    PubMed

    Ingersoll, Sarah A; Ayyadurai, Saravanan; Charania, Moiz A; Laroui, Hamed; Yan, Yutao; Merlin, Didier

    2012-03-01

    Intestinal inflammation is characterized by epithelial disruption, leading to loss of barrier function and the recruitment of immune cells, including neutrophils. Although the mechanisms are not yet completely understood, interactions between environmental and immunological factors are thought to be critical in the initiation and progression of intestinal inflammation. In recent years, it has become apparent that the di/tripeptide transporter PepT1 may play an important role in the pathogenesis of such inflammation. In healthy individuals, PepT1 is primarily expressed in the small intestine and transports di/tripeptides for metabolic purposes. However, during chronic inflammation such as that associated with inflammatory bowel disease, PepT1 expression is upregulated in the colon, wherein the protein is normally expressed either minimally or not at all. Several recent studies have shown that PepT1 binds to and transports various bacterial di/tripeptides into colon cells, leading to activation of downstream proinflammatory responses via peptide interactions with innate immune receptors. In the present review, we examine the relationship between colonic PepT1-mediated peptide transport in the colon and activation of innate immune responses during disease. It is important to understand the mechanisms of PepT1 action during chronic intestinal inflammation to develop future therapies addressing inappropriate immune activation in the colon.

  1. Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation.

    PubMed

    Sanmugapriya, E; Shanmugasundaram, P; Venkataraman, S

    2005-01-01

    In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).

  2. Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation

    PubMed Central

    Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

    2017-01-01

    Introduction The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. Aim This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Materials and Methods Albino rats of either sex were divided into five groups of six rats each (Group I – Control, Group II –Gel base, Group III –P. santalinus paste, Group IV –P. santalinus gel, Group V– Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund’s Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey’s test was used for comparison among groups. Results Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Conclusion Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation. PMID:28892928

  3. Anti-inflammatory and Analgesic Activities of Topical Formulations of Pterocarpus Santalinus Powder in Rat Model of Chronic Inflammation.

    PubMed

    Dhande, Priti Pravin; Gupta, Amit O; Jain, Sourav; Dawane, Jayshree Shriram

    2017-07-01

    The incidence of arthritis is quite high and there is a need for the search of natural products to halt the progression of disease or provide symptomatic relief without significant adverse effects. This study aimed at evaluating the anti-inflammatory and analgesic activities of topical Pterocarpus santalinus in an animal model of chronic inflammation. Albino rats of either sex were divided into five groups of six rats each (Group I - Control, Group II -Gel base, Group III -P. santalinus paste, Group IV -P. santalinus gel, Group V- Diclofenac gel). Chronic inflammation was induced on day 0 by injecting 0.1 ml Complete Freund's Adjuvant (CFA) in sub-plantar tissue of left hind paw of the rats. Topical treatment was started from day 12 till day 28. Body weight and paw volume (Plethysmometer) were assessed on day 0, 12 and 28. Pain assessment was done using Randall and Selitto paw withdrawal method. Data was analysed using GraphPad Prism version 5. Unpaired students t-test and ANOVA followed by Tukey's test was used for comparison among groups. Only topical P.santalinus gel significantly reduced the body weight (p=0.02) due to reduction in inflammatory oedema of the left limb. P. santalinus gel also showed significant reduction (p=0.03) in paw volume of rats compared to the other groups. There was significant reduction in pain threshold (gm/sec) due to chronic inflammation, with all the study drugs (p<0.05) but with P. santalinus gel, this reduction was less (p<0.001). Gel showed significant anti-inflammatory and mild analgesic activity on topical application in rat model of chronic inflammation.

  4. Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status.

    PubMed

    Huang, Xianfeng; Liu, Yuanyuan; Lu, Yingxun; Ma, Chunhua

    2015-05-01

    Acute lung injury (ALI) represents a clinical syndrome that results from complex responses of the lung to a multitude of direct and indirect insults. This study aims to evaluate the possible mechanisms responsible for the anti-inflammatory effects of eugenol (EUL) on lipopolysaccharide (LPS)-induced inflammatory reaction in ALI. ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and EUL (5, and 10 mg/kg) was injected intraperitoneally 1h prior to LPS administration. After 6h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The findings suggest that the protective mechanism of EUL may be attributed partly to decreased production of proinflammatory cytokines through the regulating inflammation and redox status. The results support that use of EUL is beneficial in the treatment of ALI.

  5. Inflammation-induced decrease in voluntary wheel running in mice: a nonreflexive test for evaluating inflammatory pain and analgesia.

    PubMed

    Cobos, Enrique J; Ghasemlou, Nader; Araldi, Dionéia; Segal, David; Duong, Kelly; Woolf, Clifford J

    2012-04-01

    Inflammatory pain impacts adversely on the quality of life of patients, often resulting in motor disabilities. Therefore, we studied the effect of peripheral inflammation induced by intraplantar administration of complete Freund's adjuvant (CFA) in mice on a particular form of voluntary locomotion, wheel running, as an index of mobility impairment produced by pain. The distance traveled over 1 hour of free access to activity wheels decreased significantly in response to hind paw inflammation, peaking 24 hours after CFA administration. Recovery of voluntary wheel running by day 3 correlated with the ability to support weight on the inflamed limb. Inflammation-induced mechanical hypersensitivity, measured with von Frey hairs, lasted considerably longer than the impaired voluntary wheel running and is not driving; therefore, the change in voluntary behavior. The CFA-induced decrease in voluntary wheel running was dose-dependently reversed by subcutaneous administration of antiinflammatory and analgesic drugs, including naproxen (10-80 mg/kg), ibuprofen (2.5-20mg/kg), diclofenac (1.25-10mg/kg), celecoxib (2.5-20mg/kg), prednisolone (0.62-5mg/kg), and morphine (0.06-0.5mg/kg), all at much lower doses than reported in most rodent models. Furthermore, the doses that induced recovery in voluntary wheel running did not reduce CFA-induced mechanical allodynia, indicating a greater sensitivity of the former as a surrogate measure of inflammatory pain. We conclude that monitoring changes in voluntary wheel running in mice during peripheral inflammation is a simple, observer-independent objective measure of functional changes produced by inflammation, likely more aligned to the global level of pain than reflexive measures, and much more sensitive to analgesic drug effects. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  6. p-Hydroxyacetophenone suppresses nuclear factor-κB-related inflammation in nociceptive and inflammatory animal models.

    PubMed

    Ching-Wen, Chang; Yun-Chieh, Chen; Yu-Chin, Lin; Wen-Huang, Peng

    2017-04-01

    p-Hydroxyacetophenone (HAP) is a crucial chemical compound present in plants of the genus Artemisia, which are used in traditional therapies for treating jaundice, hepatitis, and inflammatory diseases. Nevertheless, the bioactivity of HAP remains to be identified in order to prove its importance in the plants of genus Artemisia. This study investigated the antioxidative, antinociceptive, and anti-inflammatory effects of HAP, and probed its possible molecular mechanisms. Our results revealed that HAP (80 mg/kg, intraperitoneally) in vivo reduced the acetic acid-induced writhing response and formalin-induced licking time. Moreover, in the λ-carrageenan-induced acute-inflammatory paw edema model in mice, HAP significantly improved hind paw swelling and neutrophil infiltration. In a homogenized paw tissue examination, HAP attenuated pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-1β, and interleukin-6. Simultaneously, HAP also inhibited the production of nuclear factor kappa B, cyclooxygenase-2, and nitric oxide (NO). Another examination revealed that HAP exerted anti-inflammatory activity by decreasing malondialdehyde levels in the edematous paw through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione reductase in the liver. These findings may be beneficial in understanding the therapeutic effects of some plants of the genus Artemisia in the pretreatment of inflammation-associated diseases.

  7. RU486 blocks the anti-inflammatory effects of exercise in a murine model of allergen-induced pulmonary inflammation.

    PubMed

    Pastva, Amy; Estell, Kim; Schoeb, Trenton R; Schwiebert, Lisa M

    2005-09-01

    In an ovalbumin (OVA)-driven murine model of allergic pulmonary inflammation, we have shown previously that moderate-intensity aerobic exercise training attenuates inflammatory responses, disease progression, and NF-kappaB activation within the sensitized lung. Glucocorticoids (GCs), potent anti-inflammatory agents, have been shown to alter transcriptional events that are important in asthmatic pathogenesis, such as NF-kappaB activation. Notably, exercise training can alter the production and signaling capacity of endogenous GCs. Because GCs exert their anti-inflammatory effects through binding to intracellular glucocorticoid receptors (GRs), we examined the role of the GR in facilitating the anti-inflammatory effects of exercise. Results show that, in exercised OVA-sensitized mice, treatment with the GR antagonist RU486 blocked the exercise-induced reductions in cellular infiltration of the airways (p < .05), KC and soluble VCAM-1 protein levels in the bronchoalveloar lavage fluid (p < .05), and NF-kappaB translocation and DNA binding within the lung to levels similar to those observed in sedentary OVA-sensitized mice. Importantly, RU486 treatment also blocked exercise-induced increases in GR nuclear translocation to the levels seen in sensitized control mice. Together, these results suggest that GR nuclear translocation and NF-kappaB activation play roles in mediating the anti-inflammatory effects of exercise in allergen-mediated lung pathology.

  8. Xanomeline suppresses excessive pro-inflammatory cytokine responses through neural signal-mediated pathways and improves survival in lethal inflammation

    PubMed Central

    Rosas-Ballina, Mauricio; Ferrer, Sergio Valdés; Dancho, Meghan; Ochani, Mahendar; Katz, David; Cheng, Kai Fan; Olofsson, Peder S.; Chavan, Sangeeta S.; Al-Abed, Yousef; Tracey, Kevin J.; Pavlov, Valentin A.

    2014-01-01

    Inflammatory conditions characterized by excessive immune cell activation and cytokine release, are associated with bidirectional immune system-brain communication, underlying sickness behavior and other physiological responses. The vagus nerve has an important role in this communication by conveying sensory information to the brain, and brain-derived immunoregulatory signals that suppress peripheral cytokine levels and inflammation. Brain muscarinic acetylcholine receptor (mAChR)-mediated cholinergic signaling has been implicated in this regulation. However, the possibility of controlling inflammation by peripheral administration of centrally-acting mAChR agonists is unexplored. To provide insight we used the centrally-acting M1 mAChR agonist xanomeline, previously developed in the context of Alzheimer’s disease and schizophrenia. Intraperitoneal administration of xanomeline significantly suppressed serum and splenic TNF levels, alleviated sickness behavior, and increased survival during lethal murine endotoxemia. The anti-inflammatory effects of xanomeline were brain mAChR-mediated and required intact vagus nerve and splenic nerve signaling. The anti-inflammatory efficacy of xanomeline was retained for at least 20h, associated with alterations in splenic lymphocyte, and dendritic cell proportions, and decreased splenocyte responsiveness to endotoxin. These results highlight an important role of the M1 mAChR in a neural circuitry to spleen in which brain cholinergic activation lowers peripheral pro-inflammatory cytokines to levels favoring survival. The therapeutic efficacy of xanomeline was also manifested by significantly improved survival in preclinical settings of severe sepsis. These findings are of interest for strategizing novel therapeutic approaches in inflammatory diseases. PMID:25063706

  9. Inflammatory markers in saliva as indicators of gingival inflammation in cerebral palsy children with and without cervical motor control.

    PubMed

    Santos, Maria Teresa Botti Rodrigues; Diniz, Michele Baffi; Guaré, Renata Oliveira; Ferreira, Maria Cristina Duarte; Gutierrez, Gabriela Mancia; Gorjão, Renata

    2017-09-01

    To evaluate the relation among gingival inflammation, salivary osmolality, levels of IL-1β, IL-6, IL-8, TNF-α, and s-IgA concentrations in children with spastic CP with or without cervical motor control in a cross-sectional study. Unstimulated whole saliva and the gingival index were collected in 37 and 34 CP children with and without cervical motor control, respectively. The data were dichotomized as follows: (=0) absence of gingival inflammation and (≥0.1) presence of gingival inflammation. The group without cervical control presented statistically higher mean values of salivary osmolality, s-IgA, and cytokines. In addition, statistically positive correlation between the gingival index and salivary cytokines was observed in the group with cervical control. Salivary osmolality, salivary cytokines, and s-IgA from both groups presented a significant positive correlation. Significant differences (P = 0.00336) in the values of salivary osmolality were observed between the CP individuals with (93.9 ± 32.7) and without gingival inflammation (74.4 ± 16.6). ROC analysis was performed, and values of salivary osmolality >80 indicated a sensitivity of 0.54 and a specificity of 0.79. Children without cervical motor control presented a more pronounced oral inflammatory status that was characterized by higher levels of cytokines. © 2016 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. HTLV-1-associated inflammatory myopathies: low proviral load and moderate inflammation in 13 patients from West Indies and West Africa.

    PubMed

    Desdouits, Marion; Cassar, Olivier; Maisonobe, Thierry; Desrames, Alexandra; Aouba, Achille; Hermine, Olivier; Mikol, Jacqueline; Polivka, Marc; Penisson-Besnier, Isabelle; Marcorelles, Pascale; Zagnoli, Fabien; Papo, Thomas; Lacour, Arnaud; Amoura, Zahir; Haroche, Julien; Cherin, Patrick; Teixeira, Antonio; Benveniste, Olivier; Herson, Serge; Morin, Anne-Sophie; Mortreux, Franck; Wattel, Eric; Huerre, Michel; Cumont, Marie-Christine; Martin-Latil, Sandra; Butler-Browne, Gillian; Gout, Olivier; Taylor, Graham; Gessain, Antoine; Ozden, Simona; Ceccaldi, Pierre-Emmanuel

    2013-05-01

    The Human T-cell Leukemia Virus type 1 (HTLV-1) is the causative agent of several inflammatory diseases, including HTLV-1-associated inflammatory myopathies (HAIM). Little is known about the virological and immunological characteristics of this viral disease. To characterize the histological and virological features of HAIM patients, in order to better understand the pathogenetic mechanisms and unravel new biological markers of this disease. We conducted a retrospective study on 13 patients with HAIM, based on blood and muscle samples. We included blood samples from HTLV-1-infected individuals without myopathy as controls. Muscle biopsies were used for a broad immunohistological evaluation of tissue damage and inflammation, as well as identification of infected cells through in situ hybridization. DNA extracted from patients' PBMC was used to identify the virus genotype by sequencing and to assess the proviral load by quantitative PCR. Anti-viral antibodies in plasma samples were titrated by indirect immunofluorescence. Patients originate from HTLV-1 endemic areas, the West Indies and West Africa. Histological alterations and inflammation in patients muscles were mostly moderate, with classical features of idiopathic myositis and rare HTLV-1-infected infiltrating cells. In all patients, HTLV-1 belonged to the A subtype, transcontinental subgroup. Anti-HTLV-1 antibodies titers were high, but the proviral load was not elevated compared to asymptomatic HTLV-1 carriers. We show here that muscle inflammation is moderate in HAIM, and accompanied by a low HTLV-1 proviral load, suggesting that the pathogenetic events do not exactly mirror those of other HTLV-1-associated inflammatory diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Anti-inflammatory effects of Brazilian ginseng (Pfaffia paniculata) on TNBS-induced intestinal inflammation: Experimental evidence.

    PubMed

    Costa, C A R A; Tanimoto, A; Quaglio, A E V; Almeida, L D; Severi, J A; Di Stasi, L C

    2015-09-01

    Inflammatory bowel disease (IBD) is a chronic, relapsing, idiopathic inflammation of the gastrointestinal tract. Clinical studies suggest that the initiation of IBD is multifactorial, involving genetics, the immune system and environmental factors, such as diet, drugs and stress. Pfaffia paniculata is an adaptogenic medicinal plant used in Brazilian folk medicine as an "anti-stress" agent. Thus, we hypothesised that the P. paniculata enhances the response of animals subjected to colonic inflammation. Our aim was to investigate the intestinal anti-inflammatory activity of P. paniculata in rats before or after induction of intestinal inflammation using trinitrobenzenesulfonic acid (TNBS). The animals were divided into groups that received the vehicle, prednisolone or P. paniculata extract daily starting 14 days before or 7 days after TNBS induction. At the end of the procedure, the animals were killed and their colons were assessed for the macroscopic damage score (MDS), extent of the lesion (EL) and weight/length ratio, myeloperoxidase (MPO) activity and glutathione (GSH), cytokines and C-reactive protein (CRP) levels. Histological evaluation and ultrastructural analysis of the colonic samples were performed. Treatment with the 200mg/kg dose on the curative schedule was able to reduce the MDS and the EL. In addition, MPO activity was reduced, GSH levels were maintained, and the levels of pro-inflammatory cytokines and CRP were decreased. In conclusion, the protective effect of P. paniculata was related to reduced oxidative stress and CRP colonic levels, and due to immunomodulatory activity as evidenced by reduced levels of IL-1β, INF-γ, TNF-α and IL-6. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Anti-inflammatory effect of Man-Pen-Fang, a Chinese herbal compound, on chronic pelvic inflammation in rats.

    PubMed

    Zhang, Li-Jun; Zhu, Jian-Yong; Sun, Meng-Yao; Song, Ya-Nan; Rahman, Khalid; Peng, Cheng; Zhang, Miao; Ye, Yu-Mei; Zhang, Hong

    2017-08-17

    Traditional Chinese Medicine (TCM) has become the focus of research for the treatment of chronic pelvic inflammatory disease (CPID) based on unique medical theory system. Man-Pen-Fang (MPF), a Chinese herbal compound, which is composed of Thlaspi arvense L. (Cruciferae), Gleditsia sinensis Lam. (Leguminosae), Smilax china L. (Liliaceae), Euonymus alatus (Thunb.) Sieb. (Celastraceae) and Vaccaria segetalis (Neck.) (Caryophyllaceae) MPF has been used for the treatment of CPID and exerted significant clinical curative effects. However, the corresponding active principles and anti-inflammatory mechanism of MPF are still unknown. The objective of present study is to evaluate the effect of MPF on CPID in the chronic pelvic inflammation (CPI) rat model and elucidate its possible anti-inflammatory mechanism. The CPI in rats was induced by administration with E. coli, Staphylococcus aureus and Beta-hemolytic streptococcus. MPF (8.112g/(kg d) (20 times of adult dosage), 4.056g/(kg d) (10 times of adult dosage) and 2.028g/(kg d) (5 times of adult dosage)) and Jingangteng Capsule 2g/(kg d) (20 times of adult dosage) were administered orally for 20 days. The serum levels of five inflammation-associated cytokines (IL-2, IL-6, IL-10, TNF-α and TGF-β1) were determined by enzyme-linked immunoassay, and the mRNA expression levels of TGF-β1, P53, Fas, FasL and MMP-2 in the uterus tissue were measured by quantitative RT-PCR. Furthermore, the expression of NF-κB p65 in uterus and ovary tissues was detected by immunohistochemistry assay and the pathological changes induced in the uterus and ovary tissues were observed by histology. MPF caused a reduction in serum levels of IL-2, IL-6, IL-10, TNF-α and TGF-β1. The expression of P53 mRNA, Fas/FasL mRNA and MMP-2 mRNA in the uterus tissue was significantly elevated after treating with MPF, in contrast the expression of TGF-β1 mRNA was decreased. Furthermore, the expression of NF-κB p65 in uterus and ovary tissue was inhibited after

  13. Neutrophilia and an Anti-Inflammatory Drug as Markers of Inflammation in Delayed Muscle Soreness.

    ERIC Educational Resources Information Center

    Smith, Lucille L.; And Others

    This study reexamined the concept that delayed muscle soreness (DMS) is a form of inflammatory pain. This was accomplished by having 32 male volunteers perform exercise known to induce DMS and then assess the total and differential white blood cell changes. In addition, an anti-inflammatory drug, idomethacin, was administered to determine whether…

  14. Neutrophilia and an Anti-Inflammatory Drug as Markers of Inflammation in Delayed Muscle Soreness.

    ERIC Educational Resources Information Center

    Smith, Lucille L.; And Others

    This study reexamined the concept that delayed muscle soreness (DMS) is a form of inflammatory pain. This was accomplished by having 32 male volunteers perform exercise known to induce DMS and then assess the total and differential white blood cell changes. In addition, an anti-inflammatory drug, idomethacin, was administered to determine whether…

  15. Protective role of tumor necrosis factor (TNF) receptors in chronic intestinal inflammation: TNFR1 ablation boosts systemic inflammatory response.

    PubMed

    Wang, Yi; Han, Gencheng; Chen, Yu; Wang, Ke; Liu, Guijun; Wang, Renxi; Xiao, He; Li, Xinying; Hou, Chunmei; Shen, Beifen; Guo, Renfeng; Li, Yan; Chen, Guojiang

    2013-09-01

    Tumor necrosis factor-α (TNF-α) acts as a key factor for the development of inflammatory bowel diseases (IBDs), whose function is known to be mediated by TNF receptor 1 (TNFR1) or TNFR2. However, the precise role of the two receptors in IBD remains poorly understood. Herein, chronic colitis was established by oral administration of dextran sulfate sodium (DSS) in TNFR1 or TNFR2-/- mice. Unexpectedly, TNFR1 or TNFR2 deficiency led to exacerbation of signs of colitis compared with wild-type (WT) counterparts. Of note, TNFR1 ablation rendered significantly increased mortality compared with TNFR2 and WT mice after DSS. Aggravated pathology of colitis in TNFR1-/- or TNFR2-/- mice correlated with elevated colonic expression of proinflammatory cytokines and chemokines. Importantly, ablation of TNFR1 or TNFR2 increased apoptosis of colonic epithelial cells, which might be due to the heightened ratio of Bax/Bcl-2 and increased expression of caspase-8. Intriguingly, despite comparable intensity of intestinal inflammation in TNFR-deficient mice after DSS, systemic inflammatory response (including splenomegaly and myeloid expansion) was augmented dramatically in TNFR1-/- mice, instead of TNFR2-/- mice. Granulocyte-macrophage colony-stimulating factor (GMCSF) was identified as a key mediator in this process, as neutralization of GMCSF dampened peripheral inflammatory reaction and reduced mortality in TNFR1-/- mice. These data suggest that signaling via TNFR1 or TNFR2 has a protective role in chronic intestinal inflammation, and that lacking TNFR1 augments systemic inflammatory response in GMCSF-dependent manner.

  16. Clinical Application of Development of Nonantibiotic Macrolides That Correct Inflammation-Driven Immune Dysfunction in Inflammatory Skin Diseases

    PubMed Central

    Rodriguez-Cerdeira, Carmen; Sanchez-Blanco, Elena; Molares-Vila, Alberto

    2012-01-01

    Background. Inflammation-driven immune dysfunction supports the development of several chronic human disorders including skin diseases. Nonantibiotic macrolides have anti-inflammatory and/or immunomodulatory activity that suggests the exploitation of these in the treatment of skin diseases characterized by inflammatory disorders. Materials and Methods. We performed an extensive review of the nonantibiotic macrolide literature published between 2005 and 2012, including cross-references of any retrieved articles. We also included some data from our own experience. Results. Calcineurin antagonists such as tacrolimus and ascomycins (e.g., pimecrolimus) act by inhibiting the activation of the nuclear factor for activated T cells (NFAT). There are new applications for these macrolides that have been available for several years and have been applied to skin and hair disorders such as atopic dermatitis, oral lichen planus, vitiligo, chronic autoimmune urticaria, rosacea, alopecia areata, pyoderma gangrenosum, Behcet's disease, neutrophilic dermatosis, and lupus erythematosus. We also reviewed new macrolides, like rapamycin, everolimus, and temsirolimus. In addition to the literature review, we report a novel class of nonantibiotic 14-member macrocycle with anti-inflammatory and immunomodulatory effects. Conclusions. This paper summarizes the most important clinical studies and case reports dealing with the potential benefits of nonantibiotic macrolides which have opened new avenues in the development of anti-inflammatory strategies in the treatment of cutaneous disorders. PMID:23258954

  17. Potential anti-inflammatory effect of LQFM-021 in carrageenan-induced inflammation: The role of nitric oxide.

    PubMed

    Florentino, Iziara F; Silva, Daiany P B; Silva, Dayane M; Cardoso, Carina Sofia; Moreira, André L E; Borges, Clayton L; Soares, Célia M de A; Galdino, Pablinny M; Lião, Luciano M; Ghedini, Paulo C; Menegatti, Ricardo; Costa, Elson A

    2017-09-30

    The pyrazole compound LQFM-021 exhibits vasorelaxant, antinociceptive and anti-inflammatory activities. Furthermore, it has low toxicity, indicating that this compound may be considered to be a good prototype for the development of new analgesic/anti-inflammatory drugs. Therefore, the aim of this study was to investigate the potential anti-inflammatory activity of LQFM-021 using a model of carrageenan-induced inflammation as well as the mechanism of action and role of nitric oxide in this effect. Acute treatments with LQFM-021 (30 and 60 mg/kg p.o.) reduced paw edema formation dose-dependently 2 h after carrageenan injection. In the carrageenan-induced pleurisy test, LQFM-021 (30 mg/kg p.o.) reduced the leukocyte (polymorphonuclear) count in the pleural cavity, as well as decreased protein extravasation and myeloperoxidase activity. This dose of LQFM-021 increased the NO (nitrite/nitrate) and IL-4 levels and decreased the TNF-α and IL-1β levels in the pleural cavity. Moreover, pre-treatment with L-NAME reversed the effect of LQFM-021 on NO, leukocyte migration, and the TNF-α and IL-1β levels. Additionally, we observed that LQFM-021 showed weak inhibitory activity on cyclooxygenases, but reduced the PGE2 levels in the pleural cavity. Immunoblot analyses showed that LQFM-021 promoted a decrease in COX-2 levels and increase in iNOS levels. In conclusion, we demonstrated that LQFM-021 has marked anti-inflammatory activity by reducing polymorphonuclear recruitment, which is associated with the inhibition of the production of inflammatory cytokines and eicosanoids. In addition, we found that the synthase/release of nitric oxide promoted by LQFM-021 is essential for the anti-inflammatory effect observed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. New Echocardiographic Findings Correlate with Intramyocardial Inflammation in Endomyocardial Biopsies of Patients with Acute Myocarditis and Inflammatory Cardiomyopathy

    PubMed Central

    Escher, Felicitas; Kasner, Mario; Kühl, Uwe; Heymer, Johannes; Wilkenshoff, Ursula; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2013-01-01

    Background. The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. Methods and Results. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, −8.36 ± −3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (−9.4 ± 1.4 versus −16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Conclusion. Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi. PMID:23576857

  19. New echocardiographic findings correlate with intramyocardial inflammation in endomyocardial biopsies of patients with acute myocarditis and inflammatory cardiomyopathy.

    PubMed

    Escher, Felicitas; Kasner, Mario; Kühl, Uwe; Heymer, Johannes; Wilkenshoff, Ursula; Tschöpe, Carsten; Schultheiss, Heinz-Peter

    2013-01-01

    The diagnosis of acute myocarditis (AMC) and inflammatory cardiomyopathy (DCMi) can be difficult. Speckle tracking echocardiography with accurate assessments of regional contractility could have an outstanding importance for the diagnosis. N = 25 patients with clinically diagnosed AMC who underwent endomyocardial biopsies (EMBs) were studied prospectively. Speckle tracking imaging was examined at the beginning and during a mean follow-up period of 6.2 months. In the acute phase patients had markedly decreased left ventricular (LV) systolic function (mean LV ejection fraction (LVEF) 40.4 ± 10.3%). At follow-up in n = 8 patients, inflammation persists, correlating with a significantly reduced fractional shortening (FS, 21.5 ± 6.0%) in contrast to those without inflammation in EMB (FS 32.1 ± 7.1%, P < 0.05). All AMC patients showed a reduction in global systolic longitudinal strain (LS, -8.36 ± -3.47%) and strain rate (LSR, 0.53 ± 0.29 1/s). At follow-up, LS and LRS were significantly lower in patients with inflammation, in contrast to patients without inflammation (-9.4 ± 1.4 versus -16.8 ± 2.0%, P < 0.0001; 0.78 ± 0.4 versus 1.3 ± 0.3 1/s). LSR and LS correlate significantly with lymphocytic infiltrates (for CD3 r = 0.7, P < 0.0001, and LFA-1 r = 0.8, P < 0.0001). Speckle tracking echocardiography is a useful adjunctive assisting tool for evaluation over the course of intramyocardial inflammation in patients with AMC and DCMi.

  20. Anti-inflammatory and antinociceptive effects of salbutamol on acute and chronic models of inflammation in rats: involvement of an antioxidant mechanism.

    PubMed

    Uzkeser, Hulya; Cadirci, Elif; Halici, Zekai; Odabasoglu, Fehmi; Polat, Beyzagul; Yuksel, Tugba Nurcan; Ozaltin, Seda; Atalay, Fadime

    2012-01-01

    The possible role of β-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that the β-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulating β-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation of β-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles of β-2 adrenergic receptors in inflammatory and hyperalgesic conditions.

  1. Treatment with oral bromelain decreases colonic inflammation in the IL-10-deficient murine model of inflammatory bowel disease.

    PubMed

    Hale, Laura P; Greer, Paula K; Trinh, Chau T; Gottfried, Marcia R

    2005-08-01

    Bromelain is a mixture of proteinases derived from pineapple stem that is marketed in health food stores as a "digestive aid". Orally administered bromelain was anecdotally reported to induce clinical and endoscopic remission of ulcerative colitis in two patients whose disease was refractory to multi-agent conventional medical therapy. However, the potential efficacy of bromelain in colitis has not yet been tested rigorously in either animals or humans. In this study, the clinical and histologic severity of inflammatory bowel disease (IBD) was determined in IL-10-/- mice treated orally with bromelain in vivo. Daily treatment with oral bromelain beginning at age 5 weeks decreased the incidence and severity of spontaneous colitis in C57BL/6 IL-10-/- mice. Bromelain also significantly decreased the clinical and histologic severity of colonic inflammation when administered to piroxicam-exposed IL-10-/- mice with established colitis. Proteolytically active bromelain was required for anti-inflammatory effects in vivo. Adverse effects of dermatitis, hair loss, and weight loss due to mucositis were rare, dose related, and were not seen in wild-type mice treated orally with up to 1000 mg bromelain/kg/day for 18 weeks. Although the exact mechanisms by which exogenous proteinases affect bowel inflammation have not yet been determined, the results justify additional studies of this complementary biologically based approach to treatment of IBD.

  2. Targeting sites of inflammation: intercellular adhesion molecule-1 as a target for novel inflammatory therapies

    PubMed Central

    Hua, Susan

    2013-01-01

    Targeted drug delivery to sites of inflammation will provide effective, precise, and safe therapeutic interventions for treatment of diverse disease conditions, by limiting toxic side effects and/or increasing drug action. Disease-site targeting is believed to play a major role in the enhanced efficacy observed for a variety of drugs when formulated inside lipid vesicles. This article will focus on the factors and mechanisms involved in drug targeting to sites of inflammation and the importance of cell adhesion molecules, in particular intercellular adhesion molecule-1, in this process. PMID:24109453

  3. Anti-inflammatory Effect of Picrorhiza kurroa in Experimental Models of Inflammation.

    PubMed

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender; Raj, Arun

    2016-11-01

    Picrorhiza kurroa is an important medicinal plant in the Ayurvedic system of medicine. The root and rhizome of this plant are used for the treatment of various liver and inflammatory conditions. In the present study, we sought to investigate the anti-inflammatory activity of P. kurroa rhizome extract against carrageenan-induced paw edema and cotton pellet implantation-induced granuloma formation in rats. In addition, its immunomodulatory activity was evaluated in Complete Freund's Adjuvant-induced stimulation of a peritoneal macrophage model and lipopolysaccharide-stimulated RAW 264.7 murine macrophages. Pretreatment with P. kurroa rhizome extract inhibited carrageenan-induced paw edema and cotton pellet-induced granuloma formation in a dose-dependent manner. This was associated with reduced levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) accompanied with increased anti-inflammatory cytokine (IL-10) in the serum and peritoneal macrophages. Additionally, P. kurroa rhizome extract inhibited inflammatory TNF-receptor 1 and cyclooxygenase-2 in Complete Freund's Adjuvant-induced activated peritoneal macrophages. Furthermore, P. kurroa rhizome extract treatment significantly inhibited iNOS and suppressed the activation of NF-κB through inhibition of its phosphorylation and by blocking the activation of IκB kinase alpha in lipopolysaccharide-stimulated RAW264.7 macrophages. Taken together, these results suggest that P. kurroa has anti-inflammatory activity that is mediated through the suppression of macrophage-derived cytokine and mediators via suppression of NF-κB signaling.

  4. Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: evidence for intergenerational effects of low grade inflammation

    PubMed Central

    Kuzawa, Christopher W.; Tallman, Paula S.; Adair, Linda S.; Lee, Nanette; McDade, Thomas W.

    2012-01-01

    Background Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. Aim Evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Subjects and methods Data come from 234 parous Filipino females (21.5 ± 0.3 yr) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. Results BW in female offspring was lower only among women with high IL-1β. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p<0.104) gave birth to the largest males. Conclusion Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential intergenerational effects of chronic low-grade inflammation. PMID:22690728

  5. Inflammatory profiles in the non-pregnant state predict offspring birth weight at Cebu: evidence for inter-generational effects of low grade inflammation.

    PubMed

    Kuzawa, Christopher W; Tallman, Paula S; Adair, Linda S; Lee, Nanette; McDade, Thomas W

    2012-07-01

    Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. To evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Data come from 234 parous Filipino females (21.5 ± 0.3 years) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), tumour necrosis factor alpha (TNFα), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. BW in female offspring was lower only among women with high IL-1β. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p < 0.104) gave birth to the largest males. Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential inter-generational effects of chronic low-grade inflammation.

  6. Physical activity, by enhancing parasympathetic tone and activating the cholinergic anti-inflammatory pathway, is a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

    PubMed

    Lujan, Heidi L; DiCarlo, Stephen E

    2013-05-01

    Chronic diseases are the leading cause of death in the world and chronic inflammation is a key contributor to many chronic diseases. Accordingly, interventions that reduce inflammation may be effective in treating multiple adverse chronic conditions. In this context, physical activity is documented to reduce systemic low-grade inflammation and is acknowledged as an anti-inflammatory intervention. Furthermore, physically active individuals are at a lower risk of developing chronic diseases. However the mechanisms mediating this anti-inflammatory phenotype and range of health benefits are unknown. We hypothesize that the "cholinergic anti-inflammatory pathway" (CAP) mediates the anti-inflammatory phenotype and range of health benefits associated with physical activity. The CAP is an endogenous, physiological mechanism by which acetylcholine from the vagus nerve, interacts with the innate immune system to modulate and restrain the inflammatory cascade. Importantly, higher levels of physical activity are associated with enhanced parasympathetic (vagal) tone and lower levels of C-reactive protein, a marker of low-grade inflammation. Accordingly, physical activity, by enhancing parasympathetic tone and activating the CAP, may be a therapeutic strategy to restrain chronic inflammation and prevent many chronic diseases.

  7. Topical anti-inflammatory activities of Vitis rotundifolia (muscadine grape) extracts in the tetradecanoylphorbol acetate model of ear inflammation.

    PubMed

    Bralley, Eve E; Hargrove, James L; Greenspan, Phillip; Hartle, Diane K

    2007-12-01

    The ability of muscadine grape skin, seed, or combined skin and seed extracts to inhibit mouse ear inflammation, edema, and polymorphonuclear leukocyte infiltration was tested following topical application of 12-O-tetradecanoylphorbol 13-acetate (TPA). Ethanolic extracts of skins, seeds, or a combination of these from purple (Ison) cultivars were applied to both ears of female Swiss mice 30 minutes after TPA (2 microg per ear) administration. Control mice were treated with indomethacin or 50% ethanol vehicle 30 minutes after TPA. Ear thickness was measured before TPA and at 4 and 24 hours post-TPA administration to assess ear edema. Ear punch biopsies were collected at 24 hours and weighed as a second marker of edema. Myeloperoxidase (MPO) (EC 1.11.1.7) activity was measured in each ear punch biopsy as an index of neutrophil infiltration. Extracts of muscadine skin, seed, and combination treatments significantly reduced ear edema, ear biopsy weight, and MPO activity compared to TPA vehicle control. There was no significant difference in anti-inflammatory activity of the skin and seed extracts. However, an additive effect was observed with the combination treatment that was statistically similar to the anti-inflammatory activity of indomethacin treatment. It can be concluded that muscadine skin, seed, and combination skin/seed extracts exhibit significant topical anti-inflammatory properties.

  8. Micronutrient-gene interactions related to inflammatory/immune response and antioxidant activity in ageing and inflammation. A systematic review.

    PubMed

    Mocchegiani, Eugenio; Costarelli, Laura; Giacconi, Robertina; Malavolta, Marco; Basso, Andrea; Piacenza, Francesco; Ostan, Rita; Cevenini, Elisa; Gonos, Efstathios S; Monti, Daniela

    2014-01-01

    Recent longitudinal studies in dietary daily intake in human centenarians have shown that a satisfactory content of some micronutrients within the cells maintain several immune functions, a low grade of inflammation and preserve antioxidant activity. Micronutrients (zinc, copper, selenium) play a pivotal role in maintaining and reinforcing the performances of the immune and antioxidant systems as well as in affecting the complex network of the genes (nutrigenomic) with anti- and pro-inflammatory tasks. Genes of pro- and anti-inflammatory cytokines and some key regulators of trace elements homeostasis, such as Metallothioneins (MT), are involved in the susceptibility to major geriatric disease/disorders. Moreover, the genetic inter-individual variability may affect the nutrients' absorption (nutrigenetic) with altered effects on inflammatory/immune response and antioxidant activity. The interaction between genetic factors and micronutrients (nutrigenomic and nutrigenetic approaches) may influence ageing and longevity because the micronutrients may become also toxic. This review reports the micronutrient-gene interactions in ageing and their impact on the healthy state with a focus on the method of protein-metal speciation analysis. The association between micronutrient-gene interactions and the protein-metal speciation analysis can give a complete picture for a personalized nutrient supplementation or chelation in order to reach healthy ageing and longevity.

  9. Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation.

    PubMed

    Rialdi, Alex; Campisi, Laura; Zhao, Nan; Lagda, Arvin Cesar; Pietzsch, Colette; Ho, Jessica Sook Yuin; Martinez-Gil, Luis; Fenouil, Romain; Chen, Xiaoting; Edwards, Megan; Metreveli, Giorgi; Jordan, Stefan; Peralta, Zuleyma; Munoz-Fontela, Cesar; Bouvier, Nicole; Merad, Miriam; Jin, Jian; Weirauch, Matthew; Heinz, Sven; Benner, Chris; van Bakel, Harm; Basler, Christopher; García-Sastre, Adolfo; Bukreyev, Alexander; Marazzi, Ivan

    2016-05-27

    The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of diseases associated with exacerbated inflammation. We identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppresses the host response against influenza and Ebola viruses as well as bacterial products. Therapeutic pharmacological inhibition of Top1 protected mice from death in experimental models of lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life-threatening infections characterized by an acutely exacerbated immune response.

  10. Topoisomerase 1 inhibition suppresses inflammatory genes and protects from death by inflammation

    PubMed Central

    Zhao, Nan; Lagda, Arvin Cesar; Pietzsch, Colette; Ho, Jessica Sook Yuin; Martinez-Gil, Luis; Fenouil, Romain; Chen, Xiaoting; Edwards, Megan; Metreveli, Giorgi; Jordan, Stefan; Peralta, Zuleyma; Munoz-Fontela, Cesar; Bouvier, Nicole; Merad, Miriam; Jin, Jian; Weirauch, Matthew; Heinz, Sven; Benner, Chris; van Bakel, Harm; Basler, Christopher; García-Sastre, Adolfo; Bukreyev, Alexander; Marazzi, Ivan

    2016-01-01

    The host innate immune response is the first line of defense against pathogens and is orchestrated by the concerted expression of genes induced by microbial stimuli. Deregulated expression of these genes is linked to the initiation and progression of diseases associated with exacerbated inflammation. We identified topoisomerase 1 (Top1) as a positive regulator of RNA polymerase II transcriptional activity at pathogen-induced genes. Depletion or chemical inhibition of Top1 suppresses the host response against influenza and Ebola viruses as well as bacterial products. Therapeutic pharmacological inhibition of Top1 protected mice from death in experimental models of lethal inflammation. Our results indicate that Top1 inhibition could be used as therapy against life-threatening infections characterized by an acutely exacerbated immune response. PMID:27127234

  11. Fermented Brown Rice and Rice Bran with Aspergillus oryzae (FBRA) Prevents Inflammation-Related Carcinogenesis in Mice, through Inhibition of Inflammatory Cell Infiltration.

    PubMed

    Onuma, Kunishige; Kanda, Yusuke; Suzuki Ikeda, Saori; Sakaki, Ryuta; Nonomura, Takuya; Kobayashi, Masanobu; Osaki, Mitsuhiko; Shikanai, Masataka; Kobayashi, Hiroshi; Okada, Futoshi

    2015-12-08

    We have established an inflammation-related carcinogenesis model in mouse, in which regressive QR-32 cells subcutaneously co-implanted with a foreign body-gelatin sponge-convert themselves into lethal tumors due to massive infiltration of inflammatory cells into the sponge. Animals were fed with a diet containing 5% or 10% fermented brown rice and rice bran with Aspergillus oryzae (FBRA). In 5% and 10% FBRA diet groups, tumor incidences were lower (35% and 20%, respectively) than in the non-treated group (70%). We found that FBRA reduced the number of inflammatory cells infiltrating into the sponge. FBRA administration did not cause myelosuppression, which indicated that the anti-inflammatory effects of FBRA took place at the inflammatory lesion. FBRA did not have antitumor effects on the implanted QRsP-11 tumor cells, which is a tumorigenic cell line established from a tumor arisen after co-implantation of QR-32 cells with sponge. FBRA did not reduce formation of 8-hydroxy-2'-deoxyguanine adducts, a marker of oxidative DNA damage in the inflammatory lesion; however, it reduced expression of inflammation-related genes such as TNF-α, Mac-1, CCL3 and CXCL2. These results suggest that FBRA will be an effective chemopreventive agent against inflammation-related carcinogenesis that acts by inhibiting inflammatory cell infiltration into inflammatory lesions.

  12. Fermented Brown Rice and Rice Bran with Aspergillus oryzae (FBRA) Prevents Inflammation-Related Carcinogenesis in Mice, through Inhibition of Inflammatory Cell Infiltration

    PubMed Central

    Onuma, Kunishige; Kanda, Yusuke; Suzuki Ikeda, Saori; Sakaki, Ryuta; Nonomura, Takuya; Kobayashi, Masanobu; Osaki, Mitsuhiko; Shikanai, Masataka; Kobayashi, Hiroshi; Okada, Futoshi

    2015-01-01

    We have established an inflammation-related carcinogenesis model in mouse, in which regressive QR-32 cells subcutaneously co-implanted with a foreign body—gelatin sponge—convert themselves into lethal tumors due to massive infiltration of inflammatory cells into the sponge. Animals were fed with a diet containing 5% or 10% fermented brown rice and rice bran with Aspergillus oryzae (FBRA). In 5% and 10% FBRA diet groups, tumor incidences were lower (35% and 20%, respectively) than in the non-treated group (70%). We found that FBRA reduced the number of inflammatory cells infiltrating into the sponge. FBRA administration did not cause myelosuppression, which indicated that the anti-inflammatory effects of FBRA took place at the inflammatory lesion. FBRA did not have antitumor effects on the implanted QRsP-11 tumor cells, which is a tumorigenic cell line established from a tumor arisen after co-implantation of QR-32 cells with sponge. FBRA did not reduce formation of 8-hydroxy-2′-deoxyguanine adducts, a marker of oxidative DNA damage in the inflammatory lesion; however, it reduced expression of inflammation-related genes such as TNF-α, Mac-1, CCL3 and CXCL2. These results suggest that FBRA will be an effective chemopreventive agent against inflammation-related carcinogenesis that acts by inhibiting inflammatory cell infiltration into inflammatory lesions. PMID:26670250

  13. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria.

    PubMed

    Turner, Natalie; Wong, Hui-Li; Templeton, Arnoud; Tripathy, Sagarika; Whiti Rogers, Te; Croxford, Matthew; Jones, Ian; Sinnathamby, Mathuranthakan; Desai, Jayesh; Tie, Jeanne; Bae, Susie; Christie, Michael; Gibbs, Peter; Tran, Ben

    2016-02-01

    In Stage II colon cancer, multiple independent studies have shown that a dense intratumoural immune infiltrate (local inflammation) is associated with improved outcomes, while systemic inflammation, measured by various markers, has been associated with poorer outcomes. However, previous studies have not considered the interaction between local and systemic inflammation, nor have they assessed the type of inflammatory response compared with standard clinicopathologic criteria. In order to evaluate the potential clinical utility of inflammatory markers in Stage II colon cancer, we examined local and systemic inflammation in a consecutive series of patients with resected Stage II colon cancer between 2000 and 2010 who were identified from a prospective clinical database. Increased intratumoural chronic inflammatory cell (CIC) density, as assessed by pathologist review of hematoxylin and eosin stained slides, was used to represent local inflammation. Neutrophil-to-lymphocyte ratio (NLR) >5, as calculated from pre-operative full blood counts, was used to represent systemic inflammation. In 396 eligible patients identified, there was a non-significant inverse relationship between local and systemic inflammation. Increased CIC density was significantly associated with improved overall (HR 0.45, p = 0.001) and recurrence-free survival (HR 0.37, p = 0.003). High NLR was significantly associated with poorer overall survival (HR 2.56, p < 0.001). The combination of these markers further stratified prognosis independent of standard high-risk criteria, with a dominant systemic inflammatory response (low CIC/high NLR) associated with the worst outcome (5-year overall survival 55.8%). With further validation this simple, inexpensive combined inflammatory biomarker might assist in patient selection for adjuvant chemotherapy in Stage II colon cancer.

  14. Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor

    PubMed Central

    Agrawal, Varkha; Jaiswal, Mukesh K.; Mallers, Timothy; Katara, Gajendra K.; Gilman-Sachs, Alice; Beaman, Kenneth D.; Hirsch, Emmet

    2015-01-01

    Cellular organelles and proteins are degraded and recycled through autophagy, a process during which vesicles known as autophagosomes fuse with lysosomes. Altered autophagy occurs in various diseases, but its role in preterm labor (PTL) is unknown. We investigated the role of autophagic flux in two mouse models of PTL compared to controls: 1) inflammation-induced PTL (IPTL), induced by toll-like receptor agonists; and 2) non-inflammation (hormonally)-induced PTL (NIPTL). We demonstrate that the autophagy related genes Atg4c and Atg7 (involved in the lipidation of microtubule-associated protein 1 light chain 3 (LC3) B-I to the autophagosome-associated form, LC3B-II) decrease significantly in uterus and placenta during IPTL but not NIPTL. Autophagic flux is altered in IPTL, as shown by the accumulation of LC3B paralogues and diminishment of lysosome associated membrane protein (LAMP)-1, LAMP-2 and the a2 isoform of V-ATPase (a2V, an enzyme involved in lysosome acidification). These alterations in autophagy are associated with increased activation of NF-κB and proinflammatory cytokines/chemokines in both uterus and placenta. Similar changes are seen in macrophages exposed to TLR ligands and are enhanced with blockade of a2V. These novel findings represent the first evidence of an association between altered autophagic flux and hyper-inflammation and labor in IPTL. PMID:25797357

  15. Altered autophagic flux enhances inflammatory responses during inflammation-induced preterm labor.

    PubMed

    Agrawal, Varkha; Jaiswal, Mukesh K; Mallers, Timothy; Katara, Gajendra K; Gilman-Sachs, Alice; Beaman, Kenneth D; Hirsch, Emmet

    2015-03-23

    Cellular organelles and proteins are degraded and recycled through autophagy, a process during which vesicles known as autophagosomes fuse with lysosomes. Altered autophagy occurs in various diseases, but its role in preterm labor (PTL) is unknown. We investigated the role of autophagic flux in two mouse models of PTL compared to controls: 1) inflammation-induced PTL (IPTL), induced by toll-like receptor agonists; and 2) non-inflammation (hormonally)-induced PTL (NIPTL). We demonstrate that the autophagy related genes Atg4c and Atg7 (involved in the lipidation of microtubule-associated protein 1 light chain 3 (LC3) B-I to the autophagosome-associated form, LC3B-II) decrease significantly in uterus and placenta during IPTL but not NIPTL. Autophagic flux is altered in IPTL, as shown by the accumulation of LC3B paralogues and diminishment of lysosome associated membrane protein (LAMP)-1, LAMP-2 and the a2 isoform of V-ATPase (a2V, an enzyme involved in lysosome acidification). These alterations in autophagy are associated with increased activation of NF-κB and proinflammatory cytokines/chemokines in both uterus and placenta. Similar changes are seen in macrophages exposed to TLR ligands and are enhanced with blockade of a2V. These novel findings represent the first evidence of an association between altered autophagic flux and hyper-inflammation and labor in IPTL.

  16. Expression of Inflammation-related Intercellular Adhesion Molecules in Cardiomyocytes In Vitro and Modulation by Pro-inflammatory Agents.

    PubMed

    El-Battrawy, Ibrahim; Tülümen, Erol; Lang, Siegfried; Akin, Ibrahim; Behnes, Michael; Zhou, Xiabo; Mavany, Martin; Bugert, Peter; Bieback, Karen; Borggrefe, Martin; Elmas, Elif

    2016-01-01

    Cell-surface adhesion molecules regulate multiple intercellular and intracellular processes and play important roles in inflammation by facilitating leukocyte endothelial transmigration. Whether cardiomyocytes express surface-adhesion molecules related to inflammation and the effect of pro-inflammatory mediators remain unknown. In the present study, the expression of different cell-adhesion molecules (CD11a, CD11b, CD31, CD62P, CD162, F11 receptor and mucosal vascular addressin cell adhesion molecule 1 (MADCAM1)) and the effect of pro-inflammatory mediators were investigated in an in vitro model of human cardiomyocytes. Cells were supplied as a primary culture of cardiac alpha actin-positive cells from human heart tissue. The cells were incubated for 24 h with 1 U/ml thrombin or 700 ng/ml lipopolysaccharide (LPS) or with a combination of both. The expression of the cell adhesion molecules was measured by flow cytometry. In cultured human cardiomyocytes, 22.8% of cells expressed CD31, 7.1% MADCAM1 and 2.6% F11R. CD11a, CD11b, CD62P and CD162 were expressed by fewer than 2% of the cells at baseline. CD31 expression increased on incubation of cardiomyocytes with thrombin by 26% (p<0.05) and with LPS by 26% (p=0.06). The combination of thrombin and LPS did not result in increased levels of CD31 (p>0.10). The pro-inflammatory agents LPS and thrombin had no effect on the expression of MADCAM1 and F11R. Inflammation-related cell-adhesion molecules CD31, MADCAM1 and F11R were shown to be expressed on the surface of human cardiomyocytes in an in vitro model. Incubation with LPS or thrombin resulted in increased expression of CD31, however, it did not modify the expression of the cell adhesion molecules MADCAM1 and F11R. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  17. Yoghurt consumption regulates the immune cells implicated in acute intestinal inflammation and prevents the recurrence of the inflammatory process in a mouse model.

    PubMed

    Chaves, Silvina; Perdigon, Gabriela; de Moreno de LeBlanc, Alejandra

    2011-05-01

    Crohn's disease and ulcerative colitis, two forms of inflammatory bowel disease, are important problems in industrialized countries. The complete etiology of these two diseases is still unknown but likely involves genetic, environmental, and immunological factors. The aim of the present work was to determine whether the anti-inflammatory effects reported for yoghurt in acute trinitrobenzene sulfonic acid-induced intestinal inflammation in mice also could prevent or attenuate the recurrent intestinal inflammation, thus maintaining remission. The innate response also was evaluated through participation of Toll-like receptors (TLRs) and the analysis of T-cell populations to determine the effects of yoghurt in an acute inflammatory bowel disease model. Yoghurt exerted a beneficial effect on acute intestinal inflammation by regulating T-cell expansion and modulating the expression of TLRs, with decrease of TLR4(+) and increase of TLR9(+) cells. The anti-inflammatory effect of yoghurt also was demonstrated in a recurrent inflammation model. Yoghurt administration during the remission phase prevented the recurrence of inflammation without producing undesirable side effects. The yoghurt effect may be mediated by increased interleukin 10 production and changes in intestinal microbiota.

  18. Reflex control of inflammation by the splanchnic anti-inflammatory pathway is sustained and independent of anesthesia.

    PubMed

    Martelli, Davide; Yao, Song T; Mancera, Julian; McKinley, Michael J; McAllen, Robin M

    2014-11-01

    Following an immune challenge, there is two-way communication between the nervous and immune systems. It is proposed that a neural reflex--the inflammatory reflex--regulates the plasma levels of the key proinflammatory cytokine TNF-α, and that its efferent pathway is in the splanchnic sympathetic nerves. The evidence for this reflex is based on experiments on anesthetized animals, but anesthesia itself suppresses inflammation, confounding interpretation. Here, we show that previous section of the splanchnic nerves strongly enhances the levels of plasma TNF-α in conscious rats 90 min after they received intravenous LPS (60 μg/kg). The same reflex mechanism, therefore, applies in conscious as in anesthetized animals. In anesthetized rats, we then determined the longer-term effects of splanchnic nerve section on responses to LPS (60 μg/kg iv). We confirmed that prior splanchnic nerve section enhanced the early (90 min) peak in plasma TNF-α and found that it reduced the 90-min peak of the anti-inflammatory cytokine IL-10; both subsequently fell to low levels in all animals. Splanchnic nerve section also enhanced the delayed rise in two key proinflammatory cytokines IL-6 and interferon γ. That enhancement was undiminished after 6 h, when other measured cytokines had subsided. Finally, LPS treatment caused hypotensive shock in rats with cut splanchnic nerves but not in sham-operated animals. These findings demonstrate that reflex activation of the splanchnic anti-inflammatory pathway has a powerful and sustained restraining influence on inflammatory processes.

  19. Oxidized low density lipoprotein suppresses lipopolysaccharide-induced inflammatory responses in microglia: Oxidative stress acts through control of inflammation

    SciTech Connect

    Kim, Ohn Soon; Lee, Chang Seok; Joe, Eun-hye; Jou, Ilo . E-mail: jouilo@ajou.ac.kr

    2006-03-31

    Low density lipoprotein (LDL) is readily oxidized under certain conditions, resulting in the formation of oxidized LDL (oxLDL). Despite numerous in vitro reports that reveal the pathogenic role of oxidative stress, anti-oxidative strategies have underperformed in the clinic. In this study, we examine the role of oxLDL in brain inflammatory responses using cultured rat brain microglia. We demonstrate that oxLDL inhibits lipopolysaccharide (LPS)-induced inflammatory responses in these cells. It also decreases LPS-induced expression of inducible nitric oxide synthase and production of nitric oxide, and reduces LPS-induced secretion of tumor necrosis factor-{alpha} and monocyte chemoattractant protein-1. Oxysterols, known components of oxLDL and endogenous agonists of liver X receptor, can simulate the inhibitory effects of oxLDL in LPS-activated microglia. In addition, their inhibitory effects were mimicked by liver X receptor (LXR) agonists and potentiated by a retinoid X receptor agonist, suggesting these molecules heterodimerize to function as oxysterol receptors. Taken together, our results demonstrate that oxLDL inhibits LPS-induced inflammatory responses in brain microglia and that these inhibitory effects are mediated by oxysterols and, at least in part, by the nuclear receptor LXR. Our results suggest an additional mechanism of action for oxidative stress that acts indirectly via modulation of inflammatory responses. Although further studies are needed, these results answer in part the question of why anti-oxidative strategies have not been successful in clinical situations. Moreover, as brain inflammation participates in the initiation and progression of several neurodegenerative disorders, the present data provide information that should prove a useful guide for designing therapeutic strategies to combat oxidative brain diseases.

  20. Cytokine profile in PFAPA syndrome suggests continuous inflammation and reduced anti-inflammatory response.

    PubMed

    Stojanov, Silvia; Hoffmann, Florian; Kéry, Anja; Renner, Ellen D; Hartl, Dominik; Lohse, Peter; Huss, Kristina; Fraunberger, Peter; Malley, James D; Zellerer, Stephanie; Albert, Michael H; Belohradsky, Bernd H

    2006-06-01

    PFAPA syndrome is characterized by periodic episodes of high fever, aphthous stomatitis, pharyngitis, and/or cervical adenitis. It is of unknown etiology and manifests usually before 5 years of age. We determined serum and intracellular cytokine levels in six PFAPA patients (4 males, 2 females, mean age 8 years (+/- 1.2 SEM), range 4-13) during the symptom-free period as well as 6-12 hours and 18-24 hours after fever onset. Values were compared to age-matched, healthy controls. Febrile PFAPA attacks led to a significant increase in IL-6 and IFN-gamma serum concentrations compared to symptom-free periods and to controls, with IL-1beta, TNF-alpha and IL-12p70 levels being significantly higher than in controls. Lymphocytic IFN-gamma and CD8+ IL-2 production was consistently significantly elevated compared to healthy children. During the asymptomatic period, serum concentrations of IL-1beta, IL-6, TNF-alpha and IL-12p70 were significantly increased compared to controls. Intracellular TNF-alpha synthesis was not elevated at any time point. Soluble TNFRp55 levels were even lower in between febrile episodes, reaching values comparable to controls during attacks, whereas soluble TNFRp75 levels increased during attacks compared to healthy children. Anti-inflammatory IL-4 in serum was at all times lower in PFAPA patients compared to controls with no difference in levels of intracellular IL-4 and IL-10 or serum IL-10. The observed increase of pro-inflammatory mediators, even between febrile attacks, suggests a dysregulation of the immune response in PFAPA syndrome, with continuous pro-inflammatory cytokine activation and a reduced anti-inflammatory response.

  1. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis.

    PubMed

    Chin, Kok-Yong

    2016-01-01

    Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis.

  2. The spice for joint inflammation: anti-inflammatory role of curcumin in treating osteoarthritis

    PubMed Central

    Chin, Kok-Yong

    2016-01-01

    Osteoarthritis is a degenerative disease of the joint affecting aging populations worldwide. It has an underlying inflammatory cause, which contributes to the loss of chondrocytes, leading to diminished cartilage layer at the affected joints. Compounds with anti-inflammatory properties are potential treatment agents for osteoarthritis. Curcumin derived from Curcuma species is an anti-inflammatory compound as such. This review aims to summarize the antiosteoarthritic effects of curcumin derived from clinical and preclinical studies. Many clinical trials have been conducted to determine the effectiveness of curcumin in osteoarthritic patients. Extracts of Curcuma species, curcuminoids and enhanced curcumin, were used in these studies. Patients with osteoarthritis showed improvement in pain, physical function, and quality of life after taking curcumin. They also reported reduced concomitant usage of analgesics and side effects during treatment. In vitro studies demonstrated that curcumin could prevent the apoptosis of chondrocytes, suppress the release of proteoglycans and metal metalloproteases and expression of cyclooxygenase, prostaglandin E-2, and inflammatory cytokines in chondrocytes. These were achieved by blocking the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) system in the chondrocytes, by preventing the activation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, phosphorylation, and translocation of the p65 subunit of NF-κB complexes into the nucleus. In conclusion, curcumin is a potential candidate for the treatment of osteoarthritis. More well-planned randomized control trials and enhanced curcumin formulation are required to justify the use of curcumin in treating osteoarthritis. PMID:27703331

  3. Polyphenol metabolites from colonic microbiota exert anti-inflammatory activity on different inflammation models.

    PubMed

    Larrosa, Mar; Luceri, Cristina; Vivoli, Elisa; Pagliuca, Chiara; Lodovici, Maura; Moneti, Gloriano; Dolara, Piero

    2009-08-01

    The polyphenols in fruits and vegetables may be partly responsible for the health-promoting effects attributed to fruit and vegetable intake. Although their properties have been relatively well studied, the activity of their metabolites, produced after ingestion, has been poorly investigated. Thus, the aim of this work was to study the potential anti-inflammatory effect of 18 polyphenol metabolites, derived from colon microbiota. They were screened by measuring prostaglandin E(2) (PGE(2)) production by CCD-18 colon fibroblast cells stimulated with IL-1beta. Metabolites that inhibited more than 50% PGE(2) production were hydrocaffeic (HCAF), dihydroxyphenyl acetic (dOHPA), and hydroferulic acid (HFER), that subsequently were tested with the writhing and paw pressure test in rodents where all three compounds showed an anti-inflammatory effect. The effect of HCAF administered orally (50 mg/kg) was also tested in the dextran sodium sulfate (DSS)-induced colitis model. Weight loss and fecal water content were more pronounced in DSS rats than in DSS-HCAF treated rats. HCAF treatment diminished the expression of the cytokines IL-1beta, IL-8, and TNF-alpha, reduced malonyldialdehyde (MDA) levels and oxidative DNA damage (measured as 8-oxo-2'-deoxyguanosine levels) in distal colon mucosa. These results indicate that HCAF, dOHPA, and HFER have anti-inflammatory activity in vitro and in vivo.

  4. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

    PubMed

    Gonçalves, Pedro; Magro, Fernando; Martel, Fátima

    2015-02-01

    Epidemiological studies show that both the incidence of inflammatory bowel disease (IBD) and the proportion of people with obesity and/or obesity-associated metabolic syndrome increased markedly in developed countries during the past half century. Obesity is also associated with the development of more active IBD and requirement for hospitalization and with a decrease in the time span between diagnosis and surgery. Patients with IBD, especially Crohn's disease, present fat-wrapping or "creeping fat," which corresponds to ectopic adipose tissue extending from the mesenteric attachment and covering the majority of the small and large intestinal surface. Mesenteric adipose tissue in patients with IBD presents several morphological and functional alterations, e.g., it is more infiltrated with immune cells such as macrophages and T cells. All these lines of evidence clearly show an association between obesity, adipose tissue, and functional bowel disorders. In this review, we will show that the mesenteric adipose tissue and creeping fat are not innocent by standers but actively contribute to the intestinal and systemic inflammatory responses in patients with IBD. More specifically, we will review evidence showing that adipose tissue in IBD is associated with major alterations in the secretion of cytokines and adipokines involved in inflammatory process, in adipose tissue mesenchymal stem cells and adipogenesis, and in the interaction between adipose tissue and other intestinal components (immune, lymphatic, neuroendocrine, and intestinal epithelial systems). Collectively, these studies underline the importance of adipose tissue for the identification of novel therapeutic approaches for IBD.

  5. Local Joint inflammation and histone citrullination in a murine model of the transition from preclinical autoimmunity to inflammatory arthritis.

    PubMed

    Sohn, Dong Hyun; Rhodes, Christopher; Onuma, Kazuhiro; Zhao, Xiaoyan; Sharpe, Orr; Gazitt, Tal; Shiao, Rani; Fert-Bober, Justyna; Cheng, Danye; Lahey, Lauren J; Wong, Heidi H; Van Eyk, Jennifer; Robinson, William H; Sokolove, Jeremy

    2015-11-01

    Anti-citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition. We performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme-linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti-citrullinated H2B antibodies to mediate arthritis in vivo. We identified robust targeting of neutrophil-derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti-citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation. Our findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low-grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis

  6. Development of cerebral gray and white matter injury and cerebral inflammation over time after inflammatory perinatal asphyxia.

    PubMed

    Bonestroo, Hilde J C; Heijnen, Cobi J; Groenendaal, Floris; van Bel, Frank; Nijboer, Cora H

    2015-01-01

    Antenatal inflammation is associated with increased severity of hypoxic-ischemic (HI) encephalopathy and adverse outcome in human neonates and experimental rodents. We investigated the effect of lipopolysaccharide (LPS) on the timing of HI-induced cerebral tissue loss and gray matter injury, white matter injury and integrity, and the cerebral inflammatory response. On postnatal day 9, mice underwent HI by unilateral carotid artery occlusion followed by systemic hypoxia which resulted in early neuronal damage (MAP2 loss) at 3 h that did not increase up to day 15. LPS injection 14 h before HI (LPS+HI) significantly and gradually aggravated MAP2 loss from 3 h up to day 15, resulting in an acellular cystic lesion. LPS+HI increased white matter damage, reduced myelination in the corpus callosum and increased white matter fiber coherency in the cingulum. The number of oligodendrocytes throughout the lineage (Olig2-positive) was increased whereas more mature myelinating (CNPase-positive) oligodendrocytes were strongly decreased after LPS+HI. LPS+HI induced an increased and prolonged expression of cerebral cytokines/chemokines compared to HI. Additionally, LPS+HI increased macrophage/microglia activation and influx of neutrophils in the brain compared to HI. This study demonstrates the sensitizing effect of LPS on neonatal HI brain injury for an extended time-frame up to 15 days postinsult. LPS before HI induced a gradual increase in gray and white matter deficits, including reduced numbers of more mature myelinating oligodendrocytes and a decrease in white matter integrity. Moreover, LPS+HI prolonged and intensified the cerebral inflammatory response, including cellular infiltration. In conclusion, as the timing of damage and/or involved pathways are changed when HI is preceded by inflammation, experimental therapies might require modifications in the time window, dosage or combinations of therapies for efficacious neuroprotection. © 2015 S. Karger AG, Basel.

  7. Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

    PubMed

    Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K

    2016-04-20

    Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

  8. Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

    PubMed Central

    Ueno, Takahiro; Tsuchiya, Hironori; Mizogami, Maki; Takakura, Ko

    2008-01-01

    The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%–0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01), supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia. PMID:22096346

  9. OPN‐a induces muscle inflammation by increasing recruitment and activation of pro‐inflammatory macrophages

    PubMed Central

    Many, Gina M.; Yokosaki, Yasuyuki; Uaesoontrachoon, Kitipong; Nghiem, Peter P.; Bello, Luca; Dadgar, Sherry; Yin, Ying; Damsker, Jesse M.; Cohen, Heather B.; Kornegay, Joe N.; Bamman, Marcas M.; Mosser, David M.; Nagaraju, Kanneboyina

    2016-01-01

    New Findings What is the central question of this study? What is the functional relevance of OPN isoform expression in muscle pathology? What is the main finding and its importance? The full‐length human OPN‐a isoform is the most pro‐inflammatory isoform in the muscle microenvironment, acting on macrophages and myoblasts in an RGD‐integrin‐dependent manner. OPN‐a upregulates expression of tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Blocking TLR4 signalling inhibits the pro‐inflammatory effects of OPN‐a, suggesting that a potential mechanism of OPN action is by promoting TNC–TLR4 signalling. Although osteopontin (OPN) is an important mediator of muscle remodelling in health and disease, functional differences in human spliced OPN variants in the muscle microenvironment have not been characterized. We thus sought to define the pro‐inflammatory activities of human OPN isoforms (OPN‐a, OPN‐b and OPN‐c) on cells present in regenerating muscle. OPN transcripts were quantified in normal and dystrophic human and dog muscle. Human macrophages and myoblasts were stimulated with recombinant human OPN protein isoforms, and cytokine mRNA and protein induction was assayed. OPN isoforms were greatly increased in dystrophic human (OPN‐a > OPN‐b > OPN‐c) and dog muscle (OPN‐a = OPN‐c). In healthy human muscle, mechanical loading also upregulated OPN‐a expression (eightfold; P < 0.01), but did not significantly upregulate OPN‐c expression (twofold; P > 0.05). In vitro, OPN‐a displayed the most pronounced pro‐inflammatory activity among isoforms, acting on both macrophages and myoblasts. In vitro and in vivo data revealed that OPN‐a upregulated tenascin‐C (TNC), a known Toll‐like receptor 4 (TLR4) agonist. Inhibition of TLR4 signalling attenuated OPN‐mediated macrophage cytokine production. In summary, OPN‐a is the most abundant and functionally active human spliced isoform in the skeletal muscle

  10. Anti-inflammatory potency of nano-formulated puerarin and curcumin in rats subjected to the lipopolysaccharide-induced inflammation.

    PubMed

    Singh, Ashok K; Jiang, Yin; Gupta, Shveta; Younus, Mohamod; Ramzan, Mohamod

    2013-10-01

    Puerarin (PU) and curcumin (CU), used commonly in traditional Chinese medicine and Ayurveda, have been shown to possess potent anti-inflammatory, anti-oxidation, and neuro-protective properties. Despite the experimental success of CU and PU in in vitro and animal models, their effectiveness has not yet been demonstrated in clinical trials, possibly because of their poor bioavailability. We hypothesized that gold nanoparticle (AuNP)-formulated PU (PU-AuNP), CU (CU-AuNP), or a combination of PU and CU (PU-CU-AuNP) were a more effective and nontoxic alternative to their bulk (nonformulated) counterparts. To test the hypothesis, bioavailability, therapeutic potency, and toxicity of bulk CU and/or PU were compared with those of their nanotized counterparts in rats subjected to the lipopolysaccharide (LPS)-induced inflammation. This study showed that a 20-mg/kg dose of bulk PU or a mixture of PU and CU did not, while their nanotized counterparts, PU-AuNP, CU-AuNP, or PU-CU-AuNP, effectively suppressed the LPS-induced inflammation and cytotoxicity in rats. In addition, PU-CU-AuNP was more potent than PU-AuNP or CU-AuNP alone. The blank AuNP (bAuNP) at ≤40 mg/kg dose did not cause any adverse effects (blood and brain lactic acid concentrations, kidney function, and neuronal apoptosis were measured) in animals. Therefore, the present observations suggest that a bi-functional AuNP loaded with CU and PU may effectively suppress the LPS-induced inflammation and cytotoxicity provided the following conditions are met: (1) The AuNP dose is at or below the no-effect dose; (2) the nanoparticles release a therapeutic dose of CU and PU in vivo; and (3) the active ingredients are released into the intracellular component of the brain.

  11. Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis

    PubMed Central

    Viatte, Sebastien; Lee, James C.; Fu, Bo; Espéli, Marion; Lunt, Mark; De Wolf, Jack N. E.; Wheeler, Lily; Reynolds, John A.; Castelino, Madhura; Symmons, Deborah P. M.; Lyons, Paul A.

    2016-01-01

    Objective Genetic variation in FOXO3 (tagged by rs12212067) has been associated with a milder course of rheumatoid arthritis (RA) and shown to limit monocyte‐driven inflammation through a transforming growth factor β1–dependent pathway. This genetic association, however, has not been consistently observed in other RA cohorts. We sought to clarify the contribution of FOXO3 to prognosis in RA by combining detailed analysis of nonradiographic disease severity measures with an in vivo model of arthritis. Methods Collagen‐induced arthritis, the most commonly used mouse model of RA, was used to assess how Foxo3 contributes to arthritis severity. Using clinical, serologic, and biochemical methods, the arthritis that developed in mice carrying a loss‐of‐function mutation in Foxo3 was compared with that which occurred in littermate controls. The association of rs12212067 with nonradiographic measures of RA severity, including the C‐reactive protein level, the swollen joint count, the tender joint count, the Disease Activity Score in 28 joints, and the Health Assessment Questionnaire score, were modeled longitudinally in a large prospective cohort of patients with early RA. Results Loss of Foxo3 function resulted in more severe arthritis in vivo (both clinically and histologically) and was associated with higher titers of anticollagen antibodies and interleukin‐6 in the blood. Similarly, rs12212067 (a single‐nucleotide polymorphism that increases FOXO3 transcription) was associated with reduced inflammation, both biochemically and clinically, and with lower RA activity scores. Conclusion Consistent with its known role in restraining inflammatory responses, FOXO3 limits the severity of in vivo arthritis and, through genetic variation that increases its transcription, is associated with reduced inflammation and disease activity in RA patients, effects that result in less radiographic damage. PMID:27214848

  12. Upregulation of skeletal muscle inflammatory genes links inflammation with insulin resistance in women with the metabolic syndrome.

    PubMed

    Poelkens, Fleur; Lammers, Gerwen; Pardoel, Elisabeth M; Tack, Cees J; Hopman, Maria T E

    2013-10-01

    The metabolic syndrome, a combination of interrelated metabolic risk factors, is associated with insulin resistance and promotes the development of cardiovascular diseases and type 2 diabetes mellitus. There is a close link between inflammation and metabolic disease, but the responsible mechanisms remain elusive. The aim of this study was to identify differentially expressed genes in insulin-resistant skeletal muscle tissue of women with the metabolic syndrome compared with healthy control women. Women with the metabolic syndrome (n = 19) and healthy control women (n = 20) were extensively phenotyped, insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp, and a skeletal muscle biopsy was obtained. Gene expression levels were compared between the two groups by microarrays. The upregulated genes in skeletal muscle of the women with the metabolic syndrome were primarily enriched for inflammatory response-associated genes. The three most significantly upregulated of this group, interleukin 6 receptor (IL6R), histone deacetylase 9 (HDAC9) and CD97 molecule (CD97), were significantly correlated with insulin resistance. Taken together, these findings suggest an important role for a number of inflammatory-related genes in the development of skeletal muscle insulin resistance.

  13. Macrophage phagocytosis of neutrophils at inflammatory/infectious foci: a cooperative mechanism in the control of infection and infectious inflammation.

    PubMed

    Silva, Manuel T

    2011-05-01

    Macrophages and neutrophils possess overlapping and complementary features associated to their common origin and subsequent specialization during myelopoiesis. That specialization results in macrophage lineage being limited in antimicrobial capacity and cytotoxicity comparatively with the neutrophil lineage. These and other features of mature macrophages and neutrophils, like different lifespan and tissue localization, promote their particular lifestyles and prompt a functional partnership for cooperation in the protective antimicrobial host defense. This partnership includes reciprocal recruitment to infected sites, cooperative effector antimicrobial activities, and pro-resolving anti-inflammatory effects. One modality of the cooperative effector antimicrobial activities involves the phagocytosis by the macrophage of apoptosing neutrophils and of nonapoptosing neutrophils expressing "eat-me" signals. This cooperative interaction results in the enhancement of the comparatively limited macrophage antimicrobial capacity by the acquisition and use of potent neutrophil microbicidal molecules. Here, data are reviewed that suggest that this is a process actively engaging the two professional phagocytes. Phagocytosis of neutrophils by macrophages at inflammatory/infectious foci accumulates two effects beneficial to the protective host immune response: help in the control of the infection and prevention of neutrophil autolysis, effects that converge to accelerate the resolution of the infection-associated inflammation.

  14. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: lifestyle changes affecting the host-environment interface.

    PubMed

    Ehlers, S; Kaufmann, S H E

    2010-04-01

    In industrialized nations and high-income regions of the world, the decline of infectious diseases is paralleled by an increase in allergic, autoimmune and chronic inflammatory diseases (AACID). Changes in lifestyle in westernized societies, which impact individually and collectively on intestinal microbiota, may - at least in part - account for the AACID pandemic. Many disease genes that contribute to AACID encode pattern recognition and signalling molecules in barrier-associated cells. Interactions between gene products and environmental factors depend highly upon the host's state of maturation, the composition of the skin and gut microflora, and exposure to pollutants, antibiotics and nutrients. Inflammatory stress responses, if regulated appropriately, ensure immunity, health and relative longevity; when they are dysregulated, they can no longer be terminated appropriately and thus precipitate AACID. The 99th Dahlem Conference brought together experts of various disciplines (genetics, evolution biology, molecular biology, structural biology, cell biology, immunology, microbiology, nutrition science, epidemiology and clinical medicine) to discuss the multi-faceted relationships between infection, immunity and inflammation in barrier organs and the development of AACID. In Clinical and Experimental Immunology we are presenting a compilation of background papers that formed the basis of discussions. Controversial viewpoints and gaps in current knowledge were examined and new concepts for prevention and treatment of CID were formulated.

  15. Adoptive Transfer of Dendritic Cells Expressing Fas Ligand Modulates Intestinal Inflammation in a Model of Inflammatory Bowel Disease

    PubMed Central

    de Jesus, Edelmarie Rivera; Isidro, Raymond A; Cruz, Myrella L; Marty, Harry; Appleyard, Caroline B

    2016-01-01

    Background Inflammatory bowel diseases (IBD) are chronic relapsing inflammatory conditions of unknown cause and likely result from the loss of immunological tolerance, which leads to over-activation of the gut immune system. Gut macrophages and dendritic cells (DCs) are essential for maintaining tolerance, but can also contribute to the inflammatory response in conditions such as IBD. Current therapies for IBD are limited by high costs and unwanted toxicities and side effects. The possibility of reducing intestinal inflammation with DCs genetically engineered to over-express the apoptosis-inducing FasL (FasL-DCs) has not yet been explored. Objective Investigate the immunomodulatory effect of administering FasL-DCs in the rat trinitrobenzene sulfonic acid (TNBS) model of acute colitis. Methods Expression of FasL on DCs isolated from the mesenteric lymph nodes (MLNs) of normal and TNBS-colitis rats was determined by flow cytometry. Primary rat bone marrow DCs were transfected with rat FasL plasmid (FasL-DCs) or empty vector (EV-DCs). The effect of these DCs on T cell IFNγ secretion and apoptosis was determined by ELISPOT and flow cytometry for Annexin V, respectively. Rats received FasL-DCs or EV-DCs intraperitoneally 96 and 48 hours prior to colitis induction with TNBS. Colonic T cell and neutrophil infiltration was determined by immunohistochemistry for CD3 and myeloperoxidase activity assay, respectively. Macrophage number and phenotype was measured by double immunofluorescence for CD68 and inducible Nitric Oxide Synthase. Results MLN dendritic cells from normal rats expressed more FasL than those from colitic rats. Compared to EV-DCs, FasL-DCs reduced T cell IFNγ secretion and increased T cell apoptosis in vitro. Adoptive transfer of FasL-DCs decreased macroscopic and microscopic damage scores and reduced colonic T cells, neutrophils, and proinflammatory macrophages when compared to EV-DC adoptive transfer. Conclusion FasL-DCs are effective at treating colonic

  16. Telmisartan Attenuates Colon Inflammation, Oxidative Perturbations and Apoptosis in a Rat Model of Experimental Inflammatory Bowel Disease

    PubMed Central

    Arab, Hany H.; Al-Shorbagy, Muhammad Y.; Abdallah, Dalaal M.; Nassar, Noha N.

    2014-01-01

    Accumulating evidence has indicated the implication of angiotensin II in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. Telmisartan (TLM) is an angiotensin II receptor antagonist with marked anti-inflammatory and antioxidant actions that mediated its cardio-, reno- and hepatoprotective actions. However, its impact on IBD has not been previously explored. Thus, we aimed to investigate the potential alleviating effects of TLM in tri-nitrobenezene sulphonic acid (TNBS)-induced colitis in rats. Pretreatment with TLM (10 mg/kg p.o.) attenuated the severity of colitis as evidenced by decrease of disease activity index (DAI), colon weight/length ratio, macroscopic damage, histopathological findings and leukocyte migration. TLM suppressed the inflammatory response via attenuation of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) and myeloperoxidase (MPO) activity as a marker of neutrophil infiltration besides restoration of interleukin-10 (IL-10). TLM also suppressed mRNA and protein expression of nuclear factor kappa B (NF-κB) p65 and mRNA of cyclo-oxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proinflammatory genes with concomitant upregulation of PPAR-γ. The alleviation of TLM to colon injury was also associated with inhibition of oxidative stress as evidenced by suppression of lipid peroxides and nitric oxide (NO) besides boosting glutathione (GSH), total anti-oxidant capacity (TAC) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). With respect to apoptosis, TLM downregulated the increased mRNA, protein expression and activity of caspase-3. It also suppressed the elevation of cytochrome c and Bax mRNA besides the upregulation of Bcl-2. Together, these findings highlight evidences for the beneficial effects of TLM in IBD which are mediated through modulation of colonic inflammation, oxidative stress and apoptosis. PMID:24831514

  17. Down-regulation of PPARα in the spinal cord contributes to augmented peripheral inflammation and inflammatory hyperalgesia in diet-induced obese rats.

    PubMed

    Wang, J; Zhang, Q; Zhao, L; Li, D; Fu, Z; Liang, L

    2014-10-10

    Obesity is associated with augmented peripheral inflammation and pain sensitivity in response to inflammatory stimulation, but the underlying mechanisms remain unclear. Emerging evidence has shown that activation of peroxisome proliferator-activated receptor-α (PPARα) in the central nervous system controls peripheral inflammation and pain. We hypothesized that obesity might down-regulate PPARα in the spinal cord, leading to enhanced peripheral inflammation and inflammatory hyperalgesia. Sprague-Dawley rats fed a high-fat diet (HF) for 12weeks developed metabolic disorder and displayed significantly decreased spinal PPARα expression and activity. Interestingly, intracerebroventricular (ICV) infusion of the PPARα activator palmitoylethanolamide (PEA) in HF-fed rats for 2weeks normalized spinal PPARα expression and activity without altering metabolic parameters. HF-fed rats were more sensitive to stimulation of the inflamed paw, and exhibited more severe paw edema following carrageenan injection, whereas HF-fed rats receiving ICV PEA had similar pain sensitivity and paw edema to LF-fed rats. No difference in the expression of inflammatory mediators or nuclear factor (NF)-κB activity was observed at baseline among groups. Carrageenan induced decreased PPARα expression and activity, increased spinal cord inflammatory mediator expression and NF-κB activity in both LF-and HF-fed rats. However, the increase was more pronounced in HF-fed rats and corrected by PEA. Intrathecal injection of small interfering RNA (siRNA) against PPARα in HF-fed rats completely abolished PEA effects on peripheral pain sensitivity and paw edema. These findings suggest that diet-induced obesity causes down-regulation of spinal PPARα, which facilitates the susceptibility to peripheral inflammatory challenge by increasing inflammatory response in the spinal cord, contributing to augmented peripheral inflammation and inflammatory hyperalgesia in obesity.

  18. Does Facial Resemblance Enhance Cooperation?

    PubMed Central

    Giang, Trang; Bell, Raoul; Buchner, Axel

    2012-01-01

    Facial self-resemblance has been proposed to serve as a kinship cue that facilitates cooperation between kin. In the present study, facial resemblance was manipulated by morphing stimulus faces with the participants' own faces or control faces (resulting in self-resemblant or other-resemblant composite faces). A norming study showed that the perceived degree of kinship was higher for the participants and the self-resemblant composite faces than for actual first-degree relatives. Effects of facial self-resemblance on trust and cooperation were tested in a paradigm that has proven to be sensitive to facial trustworthiness, facial likability, and facial expression. First, participants played a cooperation game in which the composite faces were shown. Then, likability ratings were assessed. In a source memory test, participants were required to identify old and new faces, and were asked to remember whether the faces belonged to cooperators or cheaters in the cooperation game. Old-new recognition was enhanced for self-resemblant faces in comparison to other-resemblant faces. However, facial self-resemblance had no effects on the degree of cooperation in the cooperation game, on the emotional evaluation of the faces as reflected in the likability judgments, and on the expectation that a face belonged to a cooperator rather than to a cheater. Therefore, the present results are clearly inconsistent with the assumption of an evolved kin recognition module built into the human face recognition system. PMID:23094095

  19. Anti-inflammatory effect of cinnamaldehyde in Helicobacter pylori induced gastric inflammation.

    PubMed

    Muhammad, Jibran Sualeh; Zaidi, Syed Faisal; Shaharyar, Saeeda; Refaat, Alaa; Usmanghani, Khan; Saiki, Ikuo; Sugiyama, Toshiro

    2015-01-01

    Cinnamomum cassia is widely employed for gastrointestinal complaints such as dyspepsia, flatulence, diarrhea, and vomiting. Studies report cinnamaldehyde (CM) as a major active constituent of cinnamon. The aim of this study was to evaluate the anti-inflammatory mechanism of CM on Helicobacter (H.) pylori-infected gastric epithelial cells in order to validate cinnamon traditional use in gastrointestinal (GI)-related disorders. AGS/MKN-45 cells and H. pylori (193C) were employed for co-culture experiments. Anti-H. pylori cytotoxic and anti-adhesion activity of CM were determined. Enzyme linked immunosorbent assay, real time polymerase chain reaction analysis and immunoblotting were used to measure the effect on interleukin-8 (IL-8) secretion/expression. The effect on activation of nuclear factor kappa B (NF-κB) was determined by immunoblot analysis. The non-cytotoxic CM (≤125 µM) was also non-bactericidal at the given time, suggesting the effect in H. pylori/cell co-culture system was not due to alteration in H. pylori viability or the toxicity to the cells. Also, CM did not show any anti-adhesion effect against H. pylori/cell co-culture. However, pre-incubation of the cells with CM significantly inhibited the IL-8 secretion/expression from H. pylori-infected cells (p<0.01). In addition, CM suppressed H. pylori-induced NF-κB activation and prevented degradation of inhibitor (I)-κB This study provides evidence that the anti-inflammatory effect of C. cassia on H. pylori-infected gastric cells is due to blockage of the NF-κB pathway by cinnamaldehyde. This agent can be considered as a potential candidate for in vivo and clinical studies against various H. pylori related gastric pathogenic processes.

  20. Liang-Ge-San, a classic traditional Chinese medicine formula, protects against lipopolysaccharide-induced inflammation through cholinergic anti-inflammatory pathway

    PubMed Central

    Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-01-01

    Liang-Ge-San (LGS) is a classic formula in traditional Chinese medicine, which is widely used to treat acute lung injury (ALI), pharyngitis and amygdalitis in clinic. However, the underlying mechanisms remain poorly defined. In this study, we discovered that LGS exerted potent anti-inflammatory effects in lipopolysaccharide (LPS)-induced inflammation. We found that LGS significantly depressed the production of IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophage cells. The degradation and phosphorylation of IκBα and the nuclear translocation of NF-κB p65 were also inhibited. Moreover, LGS activated α7 nicotinic cholinergic receptor (α7nAchR). The blockage of α7nAchR by selective inhibitor methyllycaconitine (MLA) or α7nAchR siRNA attenuated the inhibitory effects of LGS on IκBα, NF-κB p65, IL-6 and TNF-α. Critically, LGS significantly inhibited inflammation in LPS-induced ALI rats through the activation of NF-κB signaling pathway. However, these protective effects could be counteracted by the treatment of MLA. Taken together, we first demonstrated anti-inflammatory effects of LGS both in vitro and in vivo through cholinergic anti-inflammatory pathway. The study provides a rationale for the clinical application of LGS as an anti-inflammatory agent and supports the critical role of cholinergic anti-inflammatory pathway in inflammation. PMID:27034013

  1. Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways

    PubMed Central

    Hayashi, C.; Gudino, C.V.; Gibson, F.C.; Genco, C.A.

    2010-01-01

    SUMMARY A hallmark of infection with the gram-negative pathogen Porphyromonas gingivalis is the induction of a chronic inflammatory response. P. gingivalis induces a local chronic inflammatory response that results in oral inflammatory bone destruction, which manifests as periodontal disease. In addition to chronic inflammation at the initial site of infection, mounting evidence has accumulated supporting a role for P. gingivalis-mediated periodontal disease as a risk factor for several systemic diseases including, diabetes, preterm birth, stroke, and atherosclerotic cardiovascular disease. A growing number of in vitro studies have demonstrated that P. gingivalis infection stimulates cell activation commensurate with expected responses paralleling inflammatory atherosclerotic-type responses. Furthermore, various mouse models have been used to examine the ability of P. gingivalis to stimulate chronic inflammatory plaque accumulation and recent studies have pointed to a pivotal role for innate immune signaling via the Toll-like receptors in the chronic inflammation associated with P. gingivalis infection. In this review we discuss the pathogen and host cell specificity of these responses and discuss possible mechanisms by which this oral pathogen can induce and maintain a chronic state of inflammation at sites distant from oral infection. PMID:20883220

  2. Hypothesis: Disseminated Intravascular Inflammation as the Inflammatory Counterpart to Disseminated Intravascular Coagulation

    NASA Astrophysics Data System (ADS)

    Bull, Brian S.; Bull, Maureen H.

    1994-08-01

    We have identified a leukocyte activation syndrome that is occasionally associated with the transfusion of intraoperatively recovered erythrocytes. This syndrome appears to result from intravascular damage caused by leukocytes activated during the erythrocyte salvage process. We hypothesize that this syndrome is part of a larger disease grouping: disseminated intravascular inflammation (DII). DII is the analog of the coagulation disorder disseminated intravascular coagulation. In disseminated intravascular coagulation, the organ damage results from uncontrolled activation of the clotting pathway; in DII the damage is caused by leukocytes that have become activated by direct contact with bacteria or in rare instances-such as erythrocyte salvage-in the absence of bacteria and bacterial products. Recent studies of the hazards associated with intraoperative blood salvage indicate that activation of leukocytes can be achieved by exposure to activated platelets alone. If such activated leukocytes are reinfused along with the washed erythrocytes, widespread organ damage may result. The lung is the organ most severely affected by activated leukocytes. Adult respiratory distress syndrome is one outcome. It is likely that DII is a presently unrecognized pathophysiological process that complicates a variety of primary disease states and increases their lethality.

  3. The Anti-inflammatory Effect of the CXCR4 Antagonist-N15P Peptide and Its Modulation on Inflammation-Associated Mediators in LPS-Induced PBMC.

    PubMed

    Mo, Xue-mei; Sun, Han-xiao

    2015-01-01

    Inflammation was the important pathological process of many disease developments, but current therapeutic means for inflammatory diseases are not satisfactory. Chemokines and their receptors represent valuable targets for anti-inflammatory drug discovery. The N15P polypeptide (sequence: LGASWHRPDKCCLGY) is independently developed by our research group, it is a new CXCR4 antagonist drug derived from viral macrophage inflammatory protein-II (vMIP-II). This study aims to clarify the anti-inflammatory potency of N15P polypeptide on the lipopolysaccharide (LPS)-induced inflammation in vitro. In this study, we evaluated the anti-inflammatory effects of N15P polypeptide by the LPS-induced peripheral blood mononuclear cell (PBMC) model and measured the level of inflammatory factors (tumor necrosis factor alpha (TNF-α), IL-6, IL-8, nuclear factor kappaB (NF-κB), cyclooxygenase-2 (COX-2), Toll-like receptor 4 (TLR4), MyD88, phosphoinositide 3-kinase (PI3K), and Akt). The messenger RNA (mRNA) expressions of inflammatory factors were analyzed by real-time PCR (RT-PCR) microarray analysis, and the production of inflammatory factors was measured further by enzyme-linked immunosorbent assay (ELISA) and Western blot. The results showed that the expression of inflammatory factors (TNF-α, IL-6, IL-8, NF-κB, COX-2, TLR4, MyD88, PI3K, and Akt) was downregulated by N15P peptide, suggesting that N15P peptide has a strong inhibitory effect on the inflammatory responses induced by LPS.

  4. Eicosapentaenoic acid shows anti-inflammatory effect via GPR120 in 3T3-L1 adipocytes and attenuates adipose tissue inflammation in diet-induced obese mice.

    PubMed

    Yamada, Hodaka; Umemoto, Tomio; Kakei, Masafumi; Momomura, Shin-Ichi; Kawakami, Masanobu; Ishikawa, San-E; Hara, Kazuo

    2017-01-01

    Saturated fatty acids have been shown to cause insulin resistance and low-grade chronic inflammation, whereas unsaturated fatty acids suppress inflammation via G-protein coupled receptor 120 (GPR120) in macrophages. However, the anti-inflammatory effects of unsaturated fatty acids in adipocytes have yet to be elucidated. Hence, the aims of the present study were to evaluate the anti-inflammatory effects of eicosapentaenoic acid (EPA) via GPR120 in adipocytes. We used 250 μM palmitate as a representative saturated fatty acid. 3T3-L1 adipocytes were used for in vitro studies. We further evaluated the effect of EPA supplementation in a high-fat/high-sucrose (HFHS) diet-induced adipose tissue inflammatory mouse model. EPA attenuated palmitate-induced increases in inflammatory gene expression and NF-κB phosphorylation in 3T3-L1 adipocytes. Silencing of GPR120 abolished the anti-inflammatory effects of EPA. In GPR120 downstream signal analysis, EPA was found to decrease palmitate-induced increases in TAK1/TAB1 complex expression. EPA supplementation suppressed HFHS-induced crown-like structure formation in epididymal adipose tissue and altered macrophage phenotypes from M1 to M2 in the stromal vascular fraction. Moreover, the EPA-containing diet attenuated increases in adipose p-JNK and phospho-p65 NF-κB levels. In conclusion, the findings of the present study demonstrate that EPA suppresses palmitate-induced inflammation via GPR120 by inhibiting the TAK1/TAB1 interaction in adipocytes. EPA supplementation reduced HFHS diet-induced inflammatory changes in mouse adipose tissues. These results demonstrate adipose GPR120 as a potential therapeutic target for decreasing inflammation.

  5. The proinflammatory function of lymphocytes in non-immune inflammation: effect of steroidal and non-steroidal anti-inflammatory agents.

    PubMed Central

    Leme, J. G.; Bechara, G. H.; Sudo, L. S.

    1977-01-01

    Leucopenia rendered rats unresponsive to various inflammatory stimuli. The intensity of the inflammatory response in such animals was restored by i.v. administration of suspensions of lymphocytes, but not of granulocytes. This restorative effect was blocked by both steroidal and non-steroidal anti-inflammatory drugs. Utilizing carrageenin to induce inflammatory responses in the rat's paw, the effect of these drugs on lymphocytes was observed in two circumstances. First, following incubation of the cells with the drugs in concentrations not exceeding the peak plasma levels estimated for these substances in man or laboratory animals; the effect of the drugs seemed selective, since anti-histamine and anti-serotonin agents, as well as amethopterin, were devoid of action. Second, when lymphocytes were collected from rats previously treated with the various anti-inflammatory agents, injected 6-hourly during periods of 18 and 36 h, respectively, for steroidal and non-steroidal anti-inflammatory substances. The total amounts given were lower than those required to produce consistent anti-inflammatory effects in normal animals, when the drug was given as a single dose before injection of the irritant. It is concluded that the pro-inflammatory function of lymphocytes in non-immune inflammation can be blocked by steroidal and non-steroidal anti-inflammatory agents. PMID:607989

  6. Evaluation of the Anti-Inflammatory Effect of Locally Delivered Vitamin C in the Treatment of Persistent Gingival Inflammation: Clinical and Histopathological Study

    PubMed Central

    Abdul Aziz, Manar A.; Abdel Rahman, Ahmed R.

    2016-01-01

    Objective. The purpose of this study is to investigate the role and efficiency of the locally injected vitamin C in the treatment of persistent gingival inflammation. Design. Twenty adult patients with persistent chronic gingival inflammation were included in this study. The same dose of sterile vitamin C was injected in gingival tissues after the completion of phase I therapy. Gingival biopsies were taken after total resolution of inflammation. The specimens were examined histologically, using H&E stain. Results. Clinical evaluation revealed great improvement of the injected sites with recall visits. Histopathological results revealed marked decrease in inflammatory cells and epithelial thickness and a higher number of newly formed subbasal capillaries. Conclusions. Vitamin C is an effective adjunctive treatment in reducing various degrees of chronic gingival inflammation. PMID:28050280

  7. Inflammation Mediated Metastasis: Immune Induced Epithelial-To-Mesenchymal Transition in Inflammatory Breast Cancer Cells.

    PubMed

    Cohen, Evan N; Gao, Hui; Anfossi, Simone; Mego, Michal; Reddy, Neelima G; Debeb, Bisrat; Giordano, Antonio; Tin, Sanda; Wu, Qiong; Garza, Raul J; Cristofanilli, Massimo; Mani, Sendurai A; Croix, Denise A; Ueno, Naoto T; Woodward, Wendy A; Luthra, Raja; Krishnamurthy, Savitri; Reuben, James M

    2015-01-01

    Inflammatory breast cancer (IBC) is the most insidious form of locally advanced breast cancer; about a third of patients have distant metastasis at initial staging. Emerging evidence suggests that host factors in the tumor microenvironment may interact with underlying IBC cells to make them aggressive. It is unknown whether immune cells associated to the IBC microenvironment play a role in this scenario to transiently promote epithelial to mesenchymal transition (EMT) in these cells. We hypothesized that soluble factors secreted by activated immune cells can induce an EMT in IBC and thus promote metastasis. In a pilot study of 16 breast cancer patients, TNF-α production by peripheral blood T cells was correlated with the detection of circulating tumor cells expressing EMT markers. In a variety of IBC model cell lines, soluble factors from activated T cells induced expression of EMT-related genes, including FN1, VIM, TGM2, ZEB1. Interestingly, although IBC cells exhibited increased invasion and migration following exposure to immune factors, the expression of E-cadherin (CDH1), a cell adhesion molecule, increased uniquely in IBC cell lines but not in non-IBC cell lines. A combination of TNF-α, IL-6, and TGF-β was able to recapitulate EMT induction in IBC, and conditioned media preloaded with neutralizing antibodies against these factors exhibited decreased EMT. These data suggest that release of cytokines by activated immune cells may contribute to the aggressiveness of IBC and highlight these factors as potential target mediators of immune-IBC interaction.

  8. Garcinia gardneriana (Planchon & Triana) Zappi. (Clusiaceae) as a topical anti-inflammatory alternative for cutaneous inflammation.

    PubMed

    Otuki, Michel F; Bernardi, Camila A; Prudente, Arthur S; Laskoski, Kerly; Gomig, Franciane; Horinouchi, Cintia D S; Guimarães, Claudio L; Ferreira, Juliano; Delle-Monache, Franco; Cechinel-Filho, Valdir; Cabrini, Daniela A

    2011-07-01

    Garcinia gardneriana is popularly used in skin disorders; therefore, this article investigated the effect of G. gardneriana extracts from leaves, bark and seeds and two isolated compounds in ear oedema and leucocytes migration caused by croton oil. The topical application of the extract of G. gardneriana leaves was able to reduce (70 ± 3%, and ID(50) 0.33 mg/ear) ear oedema, while the seeds (51 ± 5%) and the wood (60 ± 12%) extracts were less effective. In a time-course evaluation, the leaf extract (1 mg/ear) was effective when applied 2 hr before and until 3 hr after the stimulation, presenting a higher effectiveness when applied right after croton oil (83 ± 7% inhibition). In addition, the leaf extract was able to diminish the myeloperoxidase (MPO) activity in 64 ± 13%, which suggests the inhibition of leucocyte infiltration that was confirmed by histological analysis. Also, both biflavonoids isolated from the leaves of G. gardneriana, fukugetin (or morelloflavone) and 13-naringenin-II 8-eriodictyol (GB-2a), were able to reduce ear oedema, with ID(50) values of 0.18 (0.10-0.28) and 0.22 (0.15-0.31) mg/ear, respectively, besides the inhibition of MPO activity of 52 ± 6% and 64 ± 5%, respectively. Using the fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate, the leaf extract, fukugetin and GB-2a topically applied to the ear treated with croton oil reduced 52 ± 15%, 63 ± 17% and 83 ± 4%, respectively, the production of reactive oxygen species of the skin. Thus, these results reveal the anti-inflammatory effect of G. gardneriana leaves for topical usage, and both biflavonoids are responsible for this effect. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  9. Urinary leukotriene E4 concentrations as a potential marker of inflammation in dogs with inflammatory bowel disease.

    PubMed

    Im Hof, M; Schnyder, M; Hartnack, S; Stanke-Labesque, F; Luckschander, N; Burgener, I A

    2012-01-01

    Inflammatory bowel disease (IBD) and food-responsive diarrhea (FRD) are chronic enteropathies of dogs (CCE) that currently can only be differentiated by their response to treatment after exclusion of other diseases. In humans, increased urinary concentrations of leukotriene E4 (LTE4) have been associated with active IBD. To evaluate urinary LTE4 concentrations in dogs with IBD, FRD, and healthy controls, and to assess correlation of urinary LTE4 concentrations with the canine IBD activity index (CIBDAI) scores. Eighteen dogs with IBD, 19 dogs with FRD, and 23 healthy control dogs. In this prospective study, urine was collected and CIBDAI scores were calculated in client-owned dogs with IBD and those with FRD. Quantification of LTE4 in urine was performed by liquid chromatography-tandem mass spectrometry and corrected to creatinine. Urinary LTE4 concentrations were highest in dogs with IBD (median 85.2 pg/mg creatinine [10th-90th percentiles 10.9-372.6]) followed by those with FRD (median 31.2 pg/mg creatinine [10th-90th percentiles 6.2-114.5]) and control dogs (median 21.1 pg/mg creatinine [10th-90th percentiles 9.1-86.5]). Urinary LTE4 concentrations were higher in dogs with IBD than in control dogs (P = .011), but no significant difference between IBD and FRD was found. No correlation was found between urinary LTE4 concentrations and CIBDAI. The higher urinary LTE4 concentrations in dogs with IBD suggest that cysteinyl leukotriene pathway activation might be a component of the inflammatory process in canine IBD. Furthermore, urinary LTE4 concentrations are of potential use as a marker of inflammation in dogs with CCE. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  10. Anti-inflammatory activity of hyperimmune plasma in a lipopolysaccharide-mediated rat air pouch model of inflammation.

    PubMed

    Essien, Bryan E; Kotiw, Michael

    2012-02-01

    Tumour necrosis factor-α (TNFα) and polymorphonuclear neutrophils play key and interrelated roles in the inflammatory response against infectious agents. However, these entities can mediate significant tissue damage if their biological activity becomes deregulated. We have previously shown that canine hyperimmune frozen plasma (HFP) contains anti-TNFα activity that is attributable to elevated levels of soluble TNFα receptor 1 (sTNFR1). The aim of this study was to determine the effect of HFP on TNFα levels and neutrophil infiltration in a lipopolysaccharide (LPS)-mediated rat air pouch model of inflammation. Rats were administered either HFP, HFP which had been pre-incubated with anti-sTNFR1 antibody (5 ng/ml), fresh frozen plasma (FFP), physiological saline (PS) at 2 ml/day or Carprofen at 5 mg/kg for 3 days prior to LPS challenge. Pouch fluid was withdrawn at 1, 6, 12, 24 and 48 h post-LPS challenge and assayed for TNFα by ELISA, and for total leukocytes and neutrophils by microscopic examination. At 6 h post-LPS challenge, both TNFα levels and neutrophil counts were significantly lower in HFP-treated rats than was found in FFP, PS or Carprofen treated animals (p<0.05). In a sTNFR1 blocking experiment, incubation of HFP with anti-sTNFR1 antibody resulted in significant increases in neutrophil numbers and TNFα levels, which suggests that the anti-TNFα activity observed in HFP may be due to elevated levels of sTNFR1. The data also revealed a significant inverse correlation between total leukocyte counts and sTNFR1 levels present in pouch fluid (r= -0.73, p<0.0001). Our observations suggest that HFP warrants further investigation as a possible means for modulating acute inflammatory processes where TNFα is a key mediator.

  11. Anti-inflammatory effects of orally ingested lactoferrin and glycine in different zymosan-induced inflammation models: evidence for synergistic activity.

    PubMed

    Hartog, Anita; Leenders, Inge; van der Kraan, Peter M; Garssen, Johan

    2007-12-15

    There is a growing awareness of the interaction of food constituents with the immune system. The present study aims to evaluate the anti-inflammatory effects of two of these nutritional components (glycine and bovine-lactoferrin (b-LF)) using two different mouse models. In a zymosan-induced ear-skin inflammation model both components decreased the inflammatory response locally (ear swelling and inflammatory cytokine concentration in the ears) and systemically (number of TNF-alpha producing spleen cells). Glycine effects (20, 50 or 100 mg/mouse/day) were concentration dependent. B-LF (0.1 or 1 mg/mouse/day) inhibited the inflammatory response although higher doses (5 and 25 mg/mouse/day) were not effective. A combination of b-LF 0.1 mg/mouse/day and glycine 20 or 50 mg/mouse/day counteracted the zymosan-induced ear swelling synergistically and enhanced the decrease in the number of TNF-alpha producing spleen cells of the individual components. In a zymosan-induced acute arthritis model glycine (50 mg/mouse/day) inhibited joint swelling, inflammatory cell infiltration and cartilage proteoglycan depletion. A b-LF dose of 5 mg/mouse/day reduced the zymosan-induced joint swelling without modulating inflammatory cell infiltration and cartilage proteoglycan depletion. The present study indicates that the anti-inflammatory effects of glycine are independent of the used models. B-LF displays a reversed concentration dependency and the activity is model dependent. A combination of glycine and lactoferrin demonstrated a synergistic anti-inflammatory effect on zymosan-induced skin inflammation and an enhanced decrease in the number of TNF-alpha producing spleen cells compared to the effect of the single components. Therefore, this nutritional concept might be a new option for the treatment of chronic inflammatory diseases.

  12. Anti-inflammatory effect of rosmarinic acid and an extract of Rosmarinus officinalis in rat models of local and systemic inflammation.

    PubMed

    Rocha, Joao; Eduardo-Figueira, Maria; Barateiro, Andreia; Fernandes, Adelaide; Brites, Dora; Bronze, Rosario; Duarte, Catarina M M; Serra, Ana Teresa; Pinto, Rui; Freitas, Marisa; Fernandes, Eduarda; Silva-Lima, Beatriz; Mota-Filipe, Helder; Sepodes, Bruno

    2015-05-01

    Rosmarinic acid is a polyphenolic compound and main constituent of Rosmarinus officinalis and has been shown to possess antioxidant and anti-inflammatory properties. We aimed to evaluate the anti-inflammatory properties of rosmarinic acid and of an extract of R. officinalis in local inflammation (carrageenin-induced paw oedema model in the rat), and further evaluate the protective effect of rosmarinic acid in rat models of systemic inflammation: liver ischaemia-reperfusion (I/R) and thermal injury models. In the local inflammation model, rosmarinic acid was administered at 10, 25 and 50 mg/kg (p.o.), and the extract was administered at 10 and 25 mg/kg (equivalent doses to rosmarinic acid groups) to male Wistar rats. Administration of rosmarinic acid and extract at the dose of 25 mg/kg reduced paw oedema at 6 hr by over 60%, exhibiting a dose-response effect, suggesting that rosmarinic was the main contributor to the anti-inflammatory effect. In the liver I/R model, rosmarinic acid was administered at 25 mg/kg (i.v.) 30 min. prior to the induction of ischaemia and led to the significant reduction in the serum concentration of transaminases (AST and ALT) and LDH. In the thermal injury model, rosmarinic acid was administered at 25 mg/kg (i.v.) 5 min. prior to the induction of injury and significantly reduced multi-organ dysfunction markers (liver, kidney, lung) by modulating NF-κB and metalloproteinase-9. For the first time, the anti-inflammatory potential of rosmarinic acid has been identified, as it causes a substantial reduction in inflammation, and we speculate that it might be useful in the pharmacological modulation of injuries associated to inflammation.

  13. PEP-1-PON1 Protein Regulates Inflammatory Response in Raw 264.7 Macrophages and Ameliorates Inflammation in a TPA-Induced Animal Model

    PubMed Central

    Kim, Dae Won; Sohn, Eun Jeong; Jo, Hyo Sang; Kim, Duk-Soo; Kim, Hyun Ah; Park, Eun Young; Park, Jong Hoon; Son, Ora; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2014-01-01

    Paraoxonase 1 (PON1) is an antioxidant enzyme which plays a central role in various diseases. However, the mechanism and function of PON1 protein in inflammation are poorly understood. Since PON1 protein alone cannot be delivered into cells, we generated a cell permeable PEP-1-PON1 protein using protein transduction domains, and examined whether it can protect against cell death in lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)-treated Raw 264.7 cells as well as mice with 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin inflammation. We demonstrated that PEP-1-PON1 protein transduced into Raw 264.7 cells and markedly protected against LPS or H2O2-induced cell death by inhibiting cellular reactive oxygen species (ROS) levels, the inflammatory mediator’s expression, activation of mitogen-activated protein kinases (MAPKs) and cellular apoptosis. Furthermore, topically applied PEP-1-PON1 protein ameliorates TPA-treated mice skin inflammation via a reduction of inflammatory response. Our results indicate that PEP-1-PON1 protein plays a key role in inflammation and oxidative stress in vitro and in vivo. Therefore, we suggest that PEP-1-PON1 protein may provide a potential protein therapy against oxidative stress and inflammation. PMID:24465855

  14. PEP-1-PON1 protein regulates inflammatory response in raw 264.7 macrophages and ameliorates inflammation in a TPA-induced animal model.

    PubMed

    Kim, Mi Jin; Jeong, Hoon Jae; Kim, Dae Won; Sohn, Eun Jeong; Jo, Hyo Sang; Kim, Duk-Soo; Kim, Hyun Ah; Park, Eun Young; Park, Jong Hoon; Son, Ora; Han, Kyu Hyung; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2014-01-01

    Paraoxonase 1 (PON1) is an antioxidant enzyme which plays a central role in various diseases. However, the mechanism and function of PON1 protein in inflammation are poorly understood. Since PON1 protein alone cannot be delivered into cells, we generated a cell permeable PEP-1-PON1 protein using protein transduction domains, and examined whether it can protect against cell death in lipopolysaccharide (LPS) or hydrogen peroxide (H2O2)-treated Raw 264.7 cells as well as mice with 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced skin inflammation. We demonstrated that PEP-1-PON1 protein transduced into Raw 264.7 cells and markedly protected against LPS or H2O2-induced cell death by inhibiting cellular reactive oxygen species (ROS) levels, the inflammatory mediator's expression, activation of mitogen-activated protein kinases (MAPKs) and cellular apoptosis. Furthermore, topically applied PEP-1-PON1 protein ameliorates TPA-treated mice skin inflammation via a reduction of inflammatory response. Our results indicate that PEP-1-PON1 protein plays a key role in inflammation and oxidative stress in vitro and in vivo. Therefore, we suggest that PEP-1-PON1 protein may provide a potential protein therapy against oxidative stress and inflammation.

  15. Polyphenols from Lonicera caerulea L. Berry Inhibit LPS-Induced Inflammation through Dual Modulation of Inflammatory and Antioxidant Mediators.

    PubMed

    Wu, Shusong; Yano, Satoshi; Chen, Jihua; Hisanaga, Ayami; Sakao, Kozue; He, Xi; He, Jianhua; Hou, De-Xing

    2017-06-28

    Lonicera caerulea L. berry polyphenols (LCBP) are considered as major components for bioactivity. This study aimed to clarify the molecular mechanisms by monitoring inflammatory and antioxidant mediator actions in lipopolysaccharide (LPS)-induced mouse paw edema and macrophage cell model. LCBP significantly attenuated LPS-induced paw edema (3.0 ± 0.1 to 2.8 ± 0.1 mm, P < 0.05) and reduced (P < 0.05) serum levels of monocyte chemotactic protein-1 (MCP-1, 100.9 ± 2.3 to 58.3 ± 14.5 ng/mL), interleukin (IL)-10 (1596.1 ± 424.3 to 709.7 ± 65.7 pg/mL), macrophage inflammatory protein (MIP)-1α (1761.9 ± 208.3 to 1369.1 ± 56.4 pg/mL), IL-6 (1262.8 ± 71.7 to 499.0 ± 67.1 pg/mL), IL-4 (93.3 ± 25.7 to 50.7 ± 12.5 pg/mL), IL-12(p-70) (580.4 ± 132.0 to 315.2 ± 35.1 pg/mL), and tumor necrosis factor-α (TNF-α, 2045.5 ± 264.9 to 1270.7 ± 158.6 pg/mL). Cell signaling analysis revealed that LCBP inhibited transforming growth factor β activated kinase-1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways, and enhanced the expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and manganese-dependent superoxide dismutase (MnSOD) in earlier response. Moreover, cyanidin 3-glucoside (C3G) and (-)-epicatechin (EC), two major components of LCBP, directly bound to TAK1. These data demonstrated that LCBP might inhibit LPS-induced inflammation by modulating both inflammatory and antioxidant mediators.

  16. miRNAs as new molecular insights into inflammatory bowel disease: Crucial regulators in autoimmunity and inflammation

    PubMed Central

    Xu, Xiao-Min; Zhang, Hong-Jie

    2016-01-01

    Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammatory disorders of the gastrointestinal tract, and includes two major phenotypes: ulcerative colitis and Crohn’s disease. The pathogenesis of IBD is not fully understood as of yet. It is believed that IBD results from complicated interactions between environmental factors, genetic predisposition, and immune disorders. miRNAs are a class of small non-coding RNAs that can regulate gene expression by targeting the 3′-untranslated region of specific mRNAs for degradation or translational inhibition. miRNAs are considered to play crucial regulatory roles in many biologic processes, such as immune cellular differentiation, proliferation, and apoptosis, and maintenance of immune homeostasis. Recently, aberrant expression of miRNAs was revealed to play an important role in autoimmune diseases, including IBD. In this review, we discuss the current understanding of how miRNAs regulate autoimmunity and inflammation by affecting the differentiation, maturation, and function of various immune cells. In particular, we focus on describing specific miRNA expression profiles in tissues and peripheral blood that may be associated with the pathogenesis of IBD. In addition, we summarize the opportunities for utilizing miRNAs as new biomarkers and as potential therapeutic targets in IBD. PMID:26900285

  17. Cryptococcal meningitis accompanying lymphocytic inflammation predominantly in cerebral deep white matter: a possible manifestation of immune reconstitution inflammatory syndrome.

    PubMed

    Kuwahara, Hiroya; Tsuchiya, Kuniaki; Kobayashi, Zen; Inaba, Akira; Akiyama, Haruhiko; Mizusawa, Hidehiro

    2014-02-01

    Cryptococcal meningitis is rarely complicated by immune-mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72-year-old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro-Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome.

  18. Promoting inflammatory lymphangiogenesis by vascular endothelial growth factor-C (VEGF-C) aggravated intestinal inflammation in mice with experimental acute colitis

    PubMed Central

    Wang, X.L.; Zhao, J.; Qin, L.; Qiao, M.

    2016-01-01

    Angiogenesis and lymphangiogenesis are thought to play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, it is not understood if inflammatory lymphangiogenesis is a pathological consequence or a productive attempt to resolve the inflammation. This study investigated the effect of lymphangiogenesis on intestinal inflammation by overexpressing a lymphangiogenesis factor, vascular endothelial growth factor-C (VEGF-C), in a mouse model of acute colitis. Forty eight-week-old female C57BL/6 mice were treated with recombinant adenovirus overexpressing VEGF-C or with recombinant VEGF-C156S protein. Acute colitis was then established by exposing the mice to 5% dextran sodium sulfate (DSS) for 7 days. Mice were evaluated for disease activity index (DAI), colonic inflammatory changes, colon edema, microvessel density, lymphatic vessel density (LVD), and VEGFR-3mRNA expression in colon tissue. When acute colitis was induced in mice overexpressing VEGF-C, there was a significant increase in colonic epithelial damage, inflammatory edema, microvessel density, and neutrophil infiltration compared to control mice. These mice also exhibited increased lymphatic vessel density (73.0±3.9 vs 38.2±1.9, P<0.001) and lymphatic vessel size (1974.6±104.3 vs 1639.0±91.5, P<0.001) compared to control mice. Additionally, the expression of VEGFR-3 mRNA was significantly upregulated in VEGF-C156S mice compared to DSS-treated mice after induction of colitis (42.0±1.4 vs 3.5±0.4, P<0.001). Stimulation of lymphangiogenesis by VEGF-C during acute colitis promoted inflammatory lymphangiogenesis in the colon and aggravated intestinal inflammation. Inflammatory lymphangiogenesis may have pleiotropic effects at different stages of IBD. PMID:27074165

  19. Potential anti-inflammatory effects of maraviroc in HIV-positive patients: a pilot study of inflammation, endothelial dysfunction, and coagulation markers.

    PubMed

    Francisci, Daniela; Falcinelli, Emanuela; Baroncelli, Silvia; Petito, Eleonora; Cecchini, Enisia; Weimer, Liliana Elena; Floridia, Marco; Gresele, Paolo; Baldelli, Franco

    2014-06-01

    Persistent immune activation and chronic inflammation significantly contribute to non-AIDS morbidity in HIV-infected patients. The HIV inhibitor maraviroc (MVC) targets the cellular chemokine CCR5 HIV co-receptor, which is involved in important inflammatory pathways. MVC could have significant anti-inflammatory and anti-atherosclerotic effects, also reducing immune activation. We designed a pilot study to determine which plasma biomarkers of inflammation, endothelial dysfunction, and hypercoagulability were modified by MVC in 2 groups of 10 patients starting MVC-free or MVC-containing regimens. Ten age- and gender-matched healthy controls were also included. We found higher levels of all inflammatory biomarkers in HIV-infected patients compared to healthy controls. Both groups showed decreasing levels of interleukin (IL)-17, IL-10, and macrophage inflammatory protein (MIP)-1a following the achievement of viral suppression. Vascular cell adhesion molecule (VCAM)-1 levels were decreased in the MVC group and increased in the MVC-free group. In conclusion, some inflammatory biomarkers tend to decrease with the salvage regimen; MVC was not associated with a better impact on these measured markers.

  20. Ellagic acid ameliorates cuprizone-induced acute CNS inflammation via restriction of microgliosis and down-regulation of CCL2 and CCL3 pro-inflammatory chemokines.

    PubMed

    Sanadgol, N; Golab, F; Mostafaie, A; Mehdizadeh, M; Abdollahi, M; Sharifzadeh, M; Ravan, H

    2016-10-31

    Ellagic acid (EA) is a natural phenol antioxidant with various therapeutic activities. However, the efficacy of EA has not been examined in neuro-inflammatory conditions. Microglia making the innate immune system of the central nervous system (CNS) and are imperative cellular mediators of neuro-inflammatory processes. In this study, neuro-protective effects of EA on cuprizone (Cup)-induced acute CNS inflammation evaluated. C57BL/6J mice were fed with chow containing 0.2 % Cup for 3 weeks to induce acute neuro-inflammation predominantly in the corpus callosum (CC). EA was administered at different doses (40 or 80 mg/kg body weight/day/i.p) from the first day of the Cup diet. Microglia activation (microgliosis) and expression of microglia related chemokines during Cup challenge were examined. Results shows that EA significantly decreased the number of activated microglia cells (Iba-1+ cells) and also restricted proliferation of these cell population (Iba-1+/Ki67+ cells) in dose dependent manner. Consequently, concentration of microglial pro-inflammatory chemokines including monocyte chemoattractant protein-1/Chemokine (C-C motif) ligand 2 (MCP-1/CCL2), and macrophage inflammatory protein 1-alpha/Chemokine (C-C motif) ligand 3 (MIP-1-α/CCL3) dramatically reduced in CC after EA treatment. According to this results, we conclude that EA is a suitable therapeutic agent for moderation brain damages in neuro-inflammatory diseases.

  1. Modulation of Intestinal Inflammation by Yeasts and Cell Wall Extracts: Strain Dependence and Unexpected Anti-Inflammatory Role of Glucan Fractions

    PubMed Central

    Jawhara, Samir; Habib, Khalid; Maggiotto, François; Pignede, Georges; Vandekerckove, Pascal; Maes, Emmanuel; Dubuquoy, Laurent; Fontaine, Thierry; Guerardel, Yann; Poulain, Daniel

    2012-01-01

    Yeasts and their glycan components can have a beneficial or adverse effect on intestinal inflammation. Previous research has shown that the presence of Saccharomyces cerevisiae var. boulardii (Sb) reduces intestinal inflammation and colonization by Candida albicans. The aim of this study was to identify dietary yeasts, which have comparable effects to the anti-C. albicans and anti-inflammatory properties of Sb and to assess the capabilities of yeast cell wall components to modulate intestinal inflammation. Mice received a single oral challenge of C. albicans and were then given 1.5% dextran-sulphate-sodium (DSS) for 2 weeks followed by a 3-day restitution period. S. cerevisiae strains (Sb, Sc1 to Sc4), as well as mannoprotein (MP) and β-glucan crude fractions prepared from Sc2 and highly purified β-glucans prepared from C. albicans were used in this curative model, starting 3 days after C. albicans challenge. Mice were assessed for the clinical, histological and inflammatory responses related to DSS administration. Strain Sc1-1 gave the same level of protection against C. albicans as Sb when assessed by mortality, clinical scores, colonization levels, reduction of TNFα and increase in IL-10 transcription. When Sc1-1 was compared with the other S. cerevisiae strains, the preparation process had a strong influence on biological activity. Interestingly, some S. cerevisiae strains dramatically increased mortality and clinical scores. Strain Sc4 and MP fraction favoured C. albicans colonization and inflammation, whereas β-glucan fraction was protective against both. Surprisingly, purified β-glucans from C. albicans had the same protective effect. Thus, some yeasts appear to be strong modulators of intestinal inflammation. These effects are dependent on the strain, species, preparation process and cell wall fraction. It was striking that β-glucan fractions or pure β-glucans from C. albicans displayed the most potent anti-inflammatory effect in the DSS model. PMID

  2. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress

    SciTech Connect

    Colacino, Justin A.; Arthur, Anna E.; Ferguson, Kelly K.; Rozek, Laura S.

    2014-05-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003–2010 National Health and Nutrition Examination Survey to quantify diet's role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. - Highlights: • Cadmium may cause chronic disease through oxidative stress or inflammation. • We developed a score to quantify dietary antioxidant and anti-inflammatory intake. • Cadmium was associated with markers of oxidative stress and inflammation. • Antioxidant and anti-inflammatory intake mitigated the effects of cadmium exposure. • Dietary interventions may be effective against chronic cadmium toxicity.

  3. The Anti-Inflammatory Effect of Spray-Dried Plasma Is Mediated by a Reduction in Mucosal Lymphocyte Activation and Infiltration in a Mouse Model of Intestinal Inflammation

    PubMed Central

    Pérez-Bosque, Anna; Miró, Lluïsa; Amat, Concepció; Polo, Javier; Moretó, Miquel

    2016-01-01

    Spray-dried preparations from porcine and bovine plasma can alleviate mucosal inflammation in experimental models and improve symptoms in patients with enteropathy. In rodents, dietary supplementation with porcine spray-dried plasma (SDP) attenuates intestinal inflammation and improves the epithelial barrier function during intestinal inflammation induced by Staphylococcus aureus enterotoxin B (SEB). The aim of this study was to discern the molecular mechanisms involved in the anti-inflammatory effects of SDP. Male C57BL/6 mice were fed with 8% SDP or control diet (based on milk proteins) for two weeks, from weaning until day 33. On day 32, the mice were given a SEB dose (i.p., 25 µg/mouse) or vehicle. SEB administration increased cell recruitment to mesenteric lymph nodes and the percentage of activated Th lymphocytes and SDP prevented these effects). SDP supplementation increased the expression of interleukin 10 (IL-10) or transforming growth factor- β (TGF-β) compared to the SEB group. The SEB challenge increased six-fold the expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) and intercellular adhesion molecule 1 (ICAM-1); and these effects were attenuated by SDP supplementation. SEB also augmented NF-κB phosphorylation, an effect that was prevented by dietary SDP. Our results indicate that the anti-inflammatory effects of SDP involve the regulation of transcription factors and adhesion molecules that reduce intestinal cell infiltration and the degree of the inflammatory response. PMID:27782068

  4. The effects of grounding (earthing) on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases

    PubMed Central

    Oschman, James L; Chevalier, Gaétan; Brown, Richard

    2015-01-01

    Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing) produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1) inform researchers about what appears to be a new perspective to the study of inflammation, and 2) alert researchers that the length of time and degree (resistance to ground) of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation. PMID:25848315

  5. The effects of grounding (earthing) on inflammation, the immune response, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases.

    PubMed

    Oschman, James L; Chevalier, Gaétan; Brown, Richard

    2015-01-01

    Multi-disciplinary research has revealed that electrically conductive contact of the human body with the surface of the Earth (grounding or earthing) produces intriguing effects on physiology and health. Such effects relate to inflammation, immune responses, wound healing, and prevention and treatment of chronic inflammatory and autoimmune diseases. The purpose of this report is two-fold: to 1) inform researchers about what appears to be a new perspective to the study of inflammation, and 2) alert researchers that the length of time and degree (resistance to ground) of grounding of experimental animals is an important but usually overlooked factor that can influence outcomes of studies of inflammation, wound healing, and tumorigenesis. Specifically, grounding an organism produces measurable differences in the concentrations of white blood cells, cytokines, and other molecules involved in the inflammatory response. We present several hypotheses to explain observed effects, based on current research results and our understanding of the electronic aspects of cell and tissue physiology, cell biology, biophysics, and biochemistry. An experimental injury to muscles, known as delayed onset muscle soreness, has been used to monitor the immune response under grounded versus ungrounded conditions. Grounding reduces pain and alters the numbers of circulating neutrophils and lymphocytes, and also affects various circulating chemical factors related to inflammation.

  6. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

    PubMed Central

    DeFuria, Jason; Belkina, Anna C.; Jagannathan-Bogdan, Madhumita; Snyder-Cappione, Jennifer; Carr, Jordan David; Nersesova, Yanina R.; Markham, Douglas; Strissel, Katherine J.; Watkins, Amanda A.; Zhu, Min; Allen, Jessica; Bouchard, Jacqueline; Toraldo, Gianluca; Jasuja, Ravi; Obin, Martin S.; McDonnell, Marie E.; Apovian, Caroline; Denis, Gerald V.; Nikolajczyk, Barbara S.

    2013-01-01

    Patients with type 2 diabetes (T2D) have disease-associated changes in B-cell function, but the role these changes play in disease pathogenesis is not well established. Data herein show B cells from obese mice produce a proinflammatory cytokine profile compared with B cells from lean mice. Complementary in vivo studies show that obese B cell–null mice have decreased systemic inflammation, inflammatory B- and T-cell cytokines, adipose tissue inflammation, and insulin resistance (IR) compared with obese WT mice. Reduced inflammation in obese/insulin resistant B cell–null mice associates with an increased percentage of anti-inflammatory regulatory T cells (Tregs). This increase contrasts with the sharply decreased percentage of Tregs in obese compared with lean WT mice and suggests that B cells may be critical regulators of T-cell functions previously shown to play important roles in IR. We demonstrate that B cells from T2D (but not non-T2D) subjects support proinflammatory T-cell function in obesity/T2D through contact-dependent mechanisms. In contrast, human monocytes increase proinflammatory T-cell cytokines in both T2D and non-T2D analyses. These data support the conclusion that B cells are critical regulators of inflammation in T2D due to their direct ability to promote proinflammatory T-cell function and secrete a proinflammatory cytokine profile. Thus, B cells are potential therapeutic targets for T2D. PMID:23479618

  7. Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review.

    PubMed

    Kessel, Line; Tendal, Britta; Jørgensen, Karsten Juhl; Erngaard, Ditte; Flesner, Per; Andresen, Jens Lundgaard; Hjortdal, Jesper

    2014-10-01

    Favorable outcome after cataract surgery depends on proper control of the inflammatory response induced by cataract surgery. Pseudophakic cystoid macular edema is an important cause of visual decline after uncomplicated cataract surgery. We compared the efficacy of topical steroids with topical nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling inflammation and preventing pseudophakic cystoid macular edema (PCME) after uncomplicated cataract surgery. Patients undergoing uncomplicated surgery for age-related cataract. We performed a systematic literature search in Medline, CINAHL, Cochrane, and EMBASE databases to identify randomized trials published from 1996 onward comparing topical steroids with topical NSAIDs in controlling inflammation and preventing PCME in patients undergoing phacoemulsification with posterior chamber intraocular lens implantation for age-related cataract. Postoperative inflammation and pseudophakic cystoid macular edema. Fifteen randomized trials were identified. Postoperative inflammation was less in patients randomized to NSAIDs. The prevalence of PCME was significantly higher in the steroid group than in the NSAID group: 3.8% versus 25.3% of patients, risk ratio 5.35 (95% confidence interval, 2.94-9.76). There was no statistically significant difference in the number of adverse events in the 2 treatment groups. We found low to moderate quality of evidence that topical NSAIDs are more effective in controlling postoperative inflammation after cataract surgery. We found high-quality evidence that topical NSAIDs are more effective than topical steroids in preventing PCME. The use of topical NSAIDs was not associated with an increased events. We recommend using topical NSAIDs to prevent inflammation and PCME after routine cataract surgery. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  8. Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer.

    PubMed

    Koh, Seong-Joon; Kim, Jung Mogg; Kim, In-Kyoung; Ko, Su Hyuk; Kim, Joo Sung

    2014-03-01

    The aim of this study is to evaluate the effect of metformin on intestinal inflammation. COLO205 cells were pretreated with metformin and stimulated with tumor necrosis factor (TNF)-α. Expression of interleukin (IL)-8 was determined by luciferase assay and real-time PCR. Inhibitor of kappaB (IκB) phosphorylation/degradation and adenosine monohosphate-activated protein kinase (AMPK) activity were evaluated by Western blotting. DNA-binding activity of transcription factor nuclear factor-kappaB (NF-κB) was assessed by electrophoretic mobility shift assay. In an acute colitis model, mice were given 4% dextran sulfate sodium (DSS) for 5 days. IL-10−/− mice were used to evaluate the effect of metformin on chronic colitis. In an inflamation-associated tumor model, mice were given a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Metformin significantly inhibited IL-8 induction in COLO 205 cells stimulated with TNF-α. Metformin attenuated IκBα phosphorylation and NF-κB DNA-binding activity. Administration of metformin significantly reduced the severity of DSS-induced colitis. In addition, DSS-induced IκB kinase (IKK) activation was significantly reduced in mice treated with metformin. Metformin significantly attenuated the severity of colitis in IL-10−/− mice, induced AMPK activity in intestinal epithelial cells, and inhibited the development of colitic cancer in mice. These results indicate that metformin suppresses NF-κB activation in intestinal epithelial cells and ameliorates murine colitis and colitis-associated tumorigenesis in mice, suggesting that metformin could be a potential therapeutic agent for the treatment of inflammatory bowel disease.

  9. VEN-120, a Recombinant Human Lactoferrin, Promotes a Regulatory T Cell [Treg] Phenotype and Drives Resolution of Inflammation in Distinct Murine Models of Inflammatory Bowel Disease.

    PubMed

    MacManus, Christopher F; Collins, Colm B; Nguyen, Tom T; Alfano, Randall W; Jedlicka, Paul; de Zoeten, Edwin F

    2017-09-01

    Inflammatory bowel disease [IBD] is characterised by a disruption of immune homeostasis, which is tightly regulated to protect against harmful pathogens yet not react to commensal antigens. Animal studies indicate that regulatory T cells [Treg] modulate the immune response to prevent IBD development. Lactoferrin [LF] is an endogenous anti-inflammatory pleiotropic protein secreted at high concentrations in colostrum and at mucosal sites. However, the effect of LF on specific T lymphocyte populations has not been studied. Here, we identify a novel mechanism by which a recombinant human LF, VEN-120, regulates T cell populations in health and disease. Two murine models of intestinal inflammation, the dextran sodium sulphate colitis model and the TNFΔARE/+ model of ileitis, were used to study the anti-inflammatory and T cell modulating ability of VEN-120. Flow cytometry was used to evaluate T cell populations within the lamina propria and mesenteric lymph nodes, and to evaluate the effect of VEN-120 on CD4+ T cells in vitro. VEN-120 reduced inflammation in both models of IBD, accompanied by increased Tregs in the intestinal lamina propria. Treatment of CD4+ T cells in vitro resulted in an upregulation of Treg genes and skewing towards a Treg population. This in vitro T cell skewing translated to an increase of Treg homing to the intestinal lamina propria and associated lymph tissue in healthy mice. These data provide a novel immunological mechanism by which VEN-120 modulates T cells to restrict inflammatory T cell-driven disease.

  10. PI3K inhibitors LY294002 and IC87114 reduce inflammation in carrageenan-induced paw oedema and down-regulate inflammatory gene expression in activated macrophages.

    PubMed

    Eräsalo, Heikki; Laavola, Mirka; Hämäläinen, Mari; Leppänen, Tiina; Nieminen, Riina; Moilanen, Eeva

    2015-01-01

    PI3K/Akt pathway is a well-characterized pathway controlling cellular processes such as proliferation, migration and survival, and its role in cancer is vastly studied. There is also evidence to suggest the involvement of this pathway in the regulation of inflammatory responses. In this study, an attempt was made to investigate the role of PI3Ks in acute inflammation in vivo using pharmacological inhibitors against PI3Ks in the carrageenan-induced paw oedema model. A non-selective PI3K inhibitor LY294002 and a PI3Kδ-selective inhibitor IC87114 were used. Both of these inhibitors reduced inflammatory oedema upon carrageenan challenge in the mouse paw. To explain this result, the effects of the two inhibitors on inflammatory gene expression were investigated in activated macrophages. LY294002 and IC87114 prevented Akt phosphorylation as expected and down-regulated the expression of inflammatory factors IL-6, MCP-1,TNFα and iNOS. These findings suggest that PI3K inhibitors could be used to attenuate inflammatory responses and that the mechanism of action behind this effect is the down-regulation of inflammatory gene expression.

  11. Children's Explanations of Family Resemblances.

    ERIC Educational Resources Information Center

    Horobin, Karen D.

    Four studies investigated children's explanations for family resemblance and species-typical characteristics, under different conditions of biological parentage and rearing environment. Participating were 226 children between 3 and 11 years. Children Children were presented with a number of different tasks, some involving people and some domestic…

  12. Anti-inflammatory activity of four solvent fractions of ethanol extract of Mentha spicata L. investigated on acute and chronic inflammation induced rats.

    PubMed

    Arumugam, P; Priya, N Gayatri; Subathra, M; Ramesh, A

    2008-07-01

    Anti-inflammatory effects of four solvent fractions of ethanol extract of Mentha spicata were evaluated in acute and chronic inflammation induced in Wistar albino rats. Lipid peroxidation (LPO) and some antioxidants produced during chronic inflammation were quantitated. Hexane (320mg/kg of body weight in 25% DMSO), chloroform (320mg/kg body weight in 25% DMSO), ethyl acetate (160mg/kg body weight in 25% DMSO), aqueous (320mg/kg of body weight in ddH(2)O) fractions, two negative control groups (25% DMSO and ddH(2)O) and two anti-inflammatory drugs (Diclofenac: 25mg/kg of body weight; Indomethacin: 10mg/kg of body weight both in ddH(2)O) were administered by oral intubations to the eight groups of rats consisting six animals, each. In acute study, 1% carrageenan was injected subcutaneously in the sub-plantar region of the right hind paw after 1h of administration of test doses. The increased paw edema was measured at 0.5, 1, 2, 4, 8, 16 and 24h intervals. In the chronic study, the oral administration was carried out for seven consecutive days. On eighth day, four sterile cotton pellets (50mg each) were implanted subcutaneously in the dorsal region of the rats. On the sixteenth day, the rats were sacrificed and the cotton pellets with granulomatous tissue were dissected out and weighed (fresh and dry). Both in chronic and acute inflammation, ethyl acetate (EAF) and aqueous fraction (AF) were effective. EAF is comparable with the positive standards in chronic inflammation. The results indicate that EAF's anti-inflammatory activity is largely due to its ability to modulate in vivo antioxidants.

  13. Potentiation of indomethacin-induced anti-inflammatory response by pioglitazone in carrageenan-induced acute inflammation in rats: Role of PPARγ receptors.

    PubMed

    Houshmand, Gholamreza; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Hemmati, Ali Asghar; Hashemitabar, Mahmoud

    2016-09-01

    This study aimed to assess the interaction between anti-inflammatory effects of pioglitazone (peroxysome proliferator activated receptor-gamma (PPARγ) agonist, PGL), and indomethacin (cyclooxygenase (COX) inhibitor, IND) and to evaluate the possible underlying mechanisms. Paw edema induced by carrageenan was used to induce inflammation. Different doses of IND (0.3-10mg/kg) and PGL (1-20mg/kg) alone or in combination were administered intraperitoneally to rats. Paw tissue levels of PPARγ, COX-2, and prostaglandin E2 and serum levels of TNF-α and IL-10 were also estimated. Doses of IND and PGL showed a statistically significant anti-inflammatory effect. Combination of a non-effective dose of IND (0.3mg/kg) with increasing doses of PGL (1-10mg/kg) resulted in potentiated anti-inflammation and vise versa. IND, PGL and the combination were able to reduce the COX-2, PGE2 contents and TNF-α level. Moreover, all these treatments caused elevation in PPARγ levels and IL-10 levels. However, when the rats were pre-treated with GW-9662 (a selective PPARγ antagonist), all the anti-inflammation and alterations in the biochemical factors were antagonized. These results showed that PGL markedly enhanced the anti-inflammatory activity of IND and this effect mediated partly at least, through PPARγ. Possible mechanisms of the interaction were that PGL stimulates the PPARγ and inhibits COX-2 by those cytokines that trigger the PPARγ and also inhibit COX-2. This study suggests that combination therapy with pioglitazone and indomethacin may provide an alternative for the clinical control of inflammation especially in patients with diabetes.

  14. Anti-nociceptive and anti-inflammatory effects of cyanocobalamin (vitamin B12) against acute and chronic pain and inflammation in mice.

    PubMed

    Hosseinzadeh, H; Moallem, S A; Moshiri, M; Sarnavazi, M S; Etemad, L

    2012-07-01

    In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well. © Georg Thieme Verlag KG Stuttgart · New York.

  15. The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: Implications for a role of COX-1.

    PubMed

    Teeling, J L; Cunningham, C; Newman, T A; Perry, V H

    2010-03-01

    Systemic inflammation gives rise to metabolic and behavioural changes, largely mediated by pro-inflammatory cytokines and prostaglandin production (PGE(2)) at the blood-brain barrier. Despite numerous studies, the exact biological pathways that give rise to these changes remains elusive. This study investigated the mechanisms underlying immune-to-brain communication following systemic inflammation using various anti-inflammatory agents. Mice were pre-treated with selective cyclo-oxygenase (COX) inhibitors, thromboxane synthase inhibitors or dexamethasone, followed by intra-peritoneal injection of lipopolysaccharide (LPS). Changes in body temperature, open-field activity, and burrowing were assessed and mRNA and/or protein levels of inflammatory mediators measured in serum and brain. LPS-induced systemic inflammation resulted in behavioural changes and increased production of IL-6, IL-1beta and TNF-alpha, as well as PGE(2) in serum and brain. Indomethacin and ibuprofen reversed the effect of LPS on behaviour without changing peripheral or central IL-6, IL-1beta and TNF-alpha mRNA levels. In contrast, dexamethasone did not alter LPS-induced behavioural changes, despite complete inhibition of cytokine production. A selective COX-1 inhibitor, piroxicam, but not the selective COX-2 inhibitor, nimesulide, reversed the LPS-induced behavioural changes without affecting IL-6, IL-1beta and TNF-alpha protein expression levels in the periphery or mRNA levels in the hippocampus. Our results suggest that the acute LPS-induced changes in burrowing and open-field activity depend on COX-1. We further show that COX-1 is not responsible for the induction of brain IL-6, IL-1beta and TNF-alpha synthesis or LPS-induced hypothermia. Our results may have implications for novel therapeutic strategies to treat or prevent neurological diseases with an inflammatory component. 2009 Elsevier Inc. All rights reserved.

  16. n-3 polyunsaturated fatty acids and mechanisms to mitigate inflammatory paracrine signaling in obesity-associated breast cancer.

    PubMed

    Monk, Jennifer M; Turk, Harmony F; Liddle, Danyelle M; De Boer, Anna A; Power, Krista A; Ma, David W L; Robinson, Lindsay E

    2014-10-30

    Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer.

  17. TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention: role in chronic inflammatory diseases with an evolutionary perspective.

    PubMed

    Straub, Rainer H

    2014-09-01

    Chronic inflammatory diseases are accompanied by a systemic response of the body, necessary to redirect energy-rich fuels to the activated immune system and to induce volume expansion. The systemic response is switched on by two major pathways: (a) circulating cytokines enter the brain, and (b) signals via sensory nerve fibers are transmitted to the brain. Concerning item b, sensory nerve terminals are equipped with a multitude of receptors that sense temperature, inflammation, osmolality, and pain. Thus, they can be important to inform the brain about peripheral inflammation. Central to these sensory modalities are transient receptor potential channels (TRP channels) on sensory nerve endings. For example, TRP vanilloid 1 (TRPV1) can be activated by heat, inflammatory factors (e.g., protons, bradykinin, anandamide), hyperosmolality, pungent irritants, and others. TRP channels are multimodal switches that transmit peripheral signals to the brain, thereby inducing a systemic response. It is demonstrated how and why these TRP channels (TRPV1, TRP ankyrin type 1 (TRPA1), and TRP melastatin type 8 (TRPM8)) are important to start up a systemic response of energy expenditure, energy allocation, and water retention and how this is linked to a continuously activated immune system in chronic inflammatory diseases.

  18. TRPV1 and TRPA1 in cutaneous neurogenic and chronic inflammation: pro-inflammatory response induced by their activation and their sensitization.

    PubMed

    Gouin, Olivier; L'Herondelle, Killian; Lebonvallet, Nicolas; Le Gall-Ianotto, Christelle; Sakka, Mehdi; Buhé, Virginie; Plée-Gautier, Emmanuelle; Carré, Jean-Luc; Lefeuvre, Luc; Misery, Laurent; Le Garrec, Raphaele

    2017-03-31

    Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.

  19. Development and validation of a new model of inflammation in the cat and selection of surrogate endpoints for testing anti-inflammatory drugs.

    PubMed

    Giraudel, J M; Diquelou, A; Lees, P; Toutain, P L

    2005-06-01

    In laboratory animals many models of inflammation have been developed for preclinical evaluation of the pharmacological profiles of nonsteroidal anti-inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest, including the cat, NSAIDs have been studied mainly using dose-titration or dose-confirmation studies in clinical subjects. This is due to the scarcity of appropriate animal models and to the associated lack of quantitative validated endpoints describing the magnitude and time course of drug response. Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a powerful approach for the selection of effective and safe dosage regimens. In this study, a paw inflammation model in the cat was developed for the preclinical evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg kaolin in the paw produced a well-defined and reproducible inflammatory response that lasted 4-5 days. Several endpoints were assessed for their clinical relevance and for their metrological performance (accuracy and reproducibility). Body temperature, lameness scoring, locomotion tests and possibly skin temperature were the most appropriate endpoints for testing the antipyretic, analgesic and anti-inflammatory effects of NSAIDs in the cat.

  20. A Novel Mouse Model of Inflammatory Bowel Disease Links Mammalian Target of Rapamycin-Dependent Hyperproliferation of Colonic Epithelium to Inflammation-Associated Tumorigenesis

    PubMed Central

    Deng, Lin; Zhou, Jin-Feng; Sellers, Rani S.; Li, Jiu-Feng; Nguyen, Andrew V.; Wang, Yubao; Orlofsky, Amos; Liu, Qiang; Hume, David A.; Pollard, Jeffrey W.; Augenlicht, Leonard; Lin, Elaine Y.

    2010-01-01

    Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal cancer. However, our mechanistic understanding of the link between inflammation and tumorigenesis in the colon is limited. Here we established a novel mouse model of colitis-associated cancer by genetically inactivating signal transducer and activator of transcription 3 (Stat3) in macrophages, with partial deletion in other myeloid and lymphoid cells. Inflammation developed in the colon of mutant mice spontaneously, and tumor lesions, including invasive carcinoma, arose in the inflamed region of the intestine with a frequency similar to that observed in human IBD patients. The development of both inflammation and tumors in the mutant mice required the presence of microflora. Indeed, inflammation was associated with disruption of colonic homeostasis, fulminant epithelial/tumor cell proliferation, and activation of the mammalian target of rapamycin (mTOR)-Stat3 pathway in epithelial and tumor cells. The activation of this pathway was essential for both the excess proliferation of epithelial/tumor cells and the disruption of colonic homeostasis in the mutant mice. Notably, a similar abnormal up-regulation of mTOR-Stat3 signaling was consistently observed in the colonic epithelial cells of human IBD patients with active disease. These studies demonstrate a novel mouse model of IBD-colorectal cancer progression in which disrupted immune regulation, mTOR-Stat3 signaling, and epithelial hyperproliferation are integrated and simultaneously linked to the development of malignancy. PMID:20042677

  1. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis.

    PubMed

    Deng, Lin; Zhou, Jin-Feng; Sellers, Rani S; Li, Jiu-Feng; Nguyen, Andrew V; Wang, Yubao; Orlofsky, Amos; Liu, Qiang; Hume, David A; Pollard, Jeffrey W; Augenlicht, Leonard; Lin, Elaine Y

    2010-02-01

    Inflammatory bowel disease (IBD) is a high-risk condition for human colorectal cancer. However, our mechanistic understanding of the link between inflammation and tumorigenesis in the colon is limited. Here we established a novel mouse model of colitis-associated cancer by genetically inactivating signal transducer and activator of transcription 3 (Stat3) in macrophages, with partial deletion in other myeloid and lymphoid cells. Inflammation developed in the colon of mutant mice spontaneously, and tumor lesions, including invasive carcinoma, arose in the inflamed region of the intestine with a frequency similar to that observed in human IBD patients. The development of both inflammation and tumors in the mutant mice required the presence of microflora. Indeed, inflammation was associated with disruption of colonic homeostasis, fulminant epithelial/tumor cell proliferation, and activation of the mammalian target of rapamycin (mTOR)-Stat3 pathway in epithelial and tumor cells. The activation of this pathway was essential for both the excess proliferation of epithelial/tumor cells and the disruption of colonic homeostasis in the mutant mice. Notably, a similar abnormal up-regulation of mTOR-Stat3 signaling was consistently observed in the colonic epithelial cells of human IBD patients with active disease. These studies demonstrate a novel mouse model of IBD-colorectal cancer progression in which disrupted immune regulation, mTOR-Stat3 signaling, and epithelial hyperproliferation are integrated and simultaneously linked to the development of malignancy.

  2. IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation.

    PubMed

    Tete, S; Tripodi, D; Rosati, M; Conti, F; Maccauro, G; Saggini, A; Cianchetti, E; Caraffa, A; Antinolfi, P; Toniato, E; Castellani, M L; Conti, P; Theoharides, T C

    2012-01-01

    Cytokines such as interleukins, chemokines and interferons are immunomodulating and inflammatory agents, characterized by considerable redundancy, in that many cytokines appear to share similar functions. Virtually all nucleated cells, but especially epithelial cells and macrophages, are potent producers of cytokines. The objective of this study is to review the detailed mechanism of action and the biological profiles of IL-37, the newest anti-inflammatory cytokine. This review focuses on IL-37, a key cytokine in regulating inflammatory responses, mainly by inhibiting the expression, production and function of proinflammatory cytokines: IL-1 family pro-inflammatory effects are markedly suppressed by IL-37.

  3. Anti-inflammatory Potentials of Excretory/Secretory (ES) and Somatic Products of Marshallagia marshalli on Allergic Airway Inflammation in BALB/c Mice

    PubMed Central

    SHIRVAN, Sima PARANDE; BORJI, Hassan; MOVASSAGHI, Ahmadreza; KHAKZAD, Mohammadreza; FARZIN, Hamidreza; MALEKI, Mohsen; HAGHPARAST, Alireza

    2016-01-01

    Background: Inverse relationship between helminths infection and immune-mediated diseases has inspired researchers to investigate therapeutic potential of helminths in allergic asthma. Helminth unique ability to induce immunoregulatory responses has already been documented in several experimental studies. This study was designed to investigate whether excretory/secretory (ES) and somatic products of Marshallagia marshalli modulate the development of ovalbumin-induced airway inflammation in a mouse model. Methods: This study was carried out at the laboratories of Immunology and Parasitology of Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran during spring and summer 2015. Allergic airway inflammation was induced in mice by intraperitoneal (IP) injection with ovalbumin (OVA). The effects of ES and somatic products of M. marshalli were analyzed by inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF), pathological changes and IgE response. Results: Treatment with ES and somatic products of M. marshalli decreased cellular infiltration into BALF when they were administered during sensitization with allergen. Pathological changes were decreased in helminth-treated group, as demonstrated by reduced inflammatory cell infiltration, goblet cell hyperplasia, epithelial lesion and smooth muscle hypertrophy. However, no significant differences were observed in IgE serum levels, cytokines and eosinophil counts between different groups. Conclusion: This study provides new insights into anti-inflammatory effects of ES and somatic products of M. marshalli, during the development of non-eosinophilic model of asthma. Further study is necessary to characterize immunomodulatory molecules derived from M. marshalli as a candidate for the treatment of airway inflammation. PMID:28127363

  4. Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy.

    PubMed

    Thiele, Jan R; Habersberger, Jonathon; Braig, David; Schmidt, Yvonne; Goerendt, Kurt; Maurer, Valentin; Bannasch, Holger; Scheichl, Amelie; Woollard, Kevin J; von Dobschütz, Ernst; Kolodgie, Frank; Virmani, Renu; Stark, G Bjoern; Peter, Karlheinz; Eisenhardt, Steffen U

    2014-07-01

    The relevance of the dissociation of circulating pentameric C-reactive protein (pCRP) to its monomeric subunits (mCRP) is poorly understood. We investigated the role of conformational C-reactive protein changes in vivo. We identified mCRP in inflamed human striated muscle, human atherosclerotic plaque, and infarcted myocardium (rat and human) and its colocalization with inflammatory cells, which suggests a general causal role of mCRP in inflammation. This was confirmed in rat intravital microscopy of lipopolysaccharide-induced cremasteric muscle inflammation. Intravenous pCRP administration significantly enhanced leukocyte rolling, adhesion, and transmigration via localized dissociation to mCRP in inflamed but not noninflamed cremaster muscle. This was confirmed in a rat model of myocardial infarction. Mechanistically, this process was dependent on exposure of lysophosphatidylcholine on activated cell membranes, which is generated after phospholipase A2 activation. These membrane changes could be visualized intravitally on endothelial cells, as could the colocalized mCRP generation. Blocking of phospholipase A2 abrogated C-reactive protein dissociation and thereby blunted the proinflammatory effects of C-reactive protein. Identifying the dissociation process as a therapeutic target, we stabilized pCRP using 1,6-bis(phosphocholine)-hexane, which prevented dissociation in vitro and in vivo and consequently inhibited the generation and proinflammatory activity of mCRP; notably, it also inhibited mCRP deposition and inflammation in rat myocardial infarction. These results provide in vivo evidence for a novel mechanism that localizes and aggravates inflammation via phospholipase A2-dependent dissociation of circulating pCRP to mCRP. mCRP is proposed as a pathogenic factor in atherosclerosis and myocardial infarction. Most importantly, the inhibition of pCRP dissociation represents a promising, novel anti-inflammatory therapeutic strategy. © 2014 American Heart

  5. Alpha-Lipoic Acid Alleviates Acute Inflammation and Promotes Lipid Mobilization During the Inflammatory Response in White Adipose Tissue of Mice.

    PubMed

    Guo, Jun; Gao, Shixing; Liu, Zhiqing; Zhao, Ruqian; Yang, Xiaojing

    2016-10-01

    Recently, white adipose tissue has been shown to exhibit immunological activity, and may play an important role in host defense and protection against bacterial infection. Αlpha-lipoic acid (α-LA) has been demonstrated to function as an anti-inflammatory and anti-oxidant agent. However, its influence on the inflammatory response and metabolic changes in white adipose tissue remains unknown. We used male C57BL/6 mice as models to study the effect of α-LA on the inflammatory response and metabolic changes in white adipose tissue after stimulation with lipopolysaccharide (LPS). The non-esterified fatty acid content was measured by an automatic biochemical analyzer. The expression of inflammation-, lipid- and energy metabolism-related genes and proteins was determined by quantitative real-time polymerase chain reaction and western blotting. The results indicated that α-LA significantly decreased the epididymis fat weight index and the non-esterified fatty acid content in plasma compared with the control group. LPS significantly increased the expression of inflammation genes and α-LA reduced their expression. The LPS-induced expression of nuclear factor-κB protein was decreased by α-LA. Regarding lipid metabolism, α-LA significantly counteracted the inhibitory effects of LPS on the expression of hormone-sensitive lipase gene and protein. α-LA evidently increased the gene expression of fatty acid transport protein 1 and cluster of differentiation 36. Regarding energy metabolism, α-LA significantly increased the expression of most of mitochondrial DNA-encoded genes compared with the control and LPS group. Accordingly, α-LA can alleviate acute inflammatory response and this action may be related with the promotion of lipid mobilization in white adipose tissue.

  6. [Role of anti-inflammatory drugs in the treatment of acute coronary syndromes. From athero-inflammation to athero-thrombosis].

    PubMed

    Altman, Raúl; Scazziota, Alejandra

    2003-01-01

    Coronary thrombosis is the most important cause of morbidity and mortality and the most severe manifestation of atherosclerosis. Knowledge of the pathophysiology of atheroma formation and the causes of atheroma accidents have allowed the development of new therapeutic measures for reducing thrombotic events after a coronary episode. Treating the thrombosis after plaque rupture is useful, but a late measure once coronary flow is disturbed. Therefore, treatment at an earlier stage, which we call athero-inflammation, a central event in atheroma progression leading to atherothrombosis, seems wise. There is evidence of an inflammatory component in the pathogenesis of atheroma rupture in acute coronary events. Earlier studies of anti-inflammatory medication have not demonstrated a reduction in thrombotic complications after an acute coronary episode. However, there are pathophysiological arguments and clinical findings that suggest that it would be advisable to include anti-inflammatory medications, especially those that inhibit preferentially COX-2, in the therapeutic arsenal for this pathology. We postulated that blocking athero-inflammation could prevent thrombosis. A pilot study was carried out in 120 patients with acute coronary syndrome without ST-segment elevation in which 60 patients were treated with meloxicam, a preferential COX-2 inhibitor. All patients received heparin and aspirin. During the stay in the coronary care unit, as well as after 90 days, meloxicam lowered composite outcomes (myocardial infarction, death and revascularization procedures) compared with the control group. These results and available pathophysiological and clinical evidence support the hypothesis of potential benefits of non-steroidal anti-inflammatory drugs with preferential inhibitory activity on COX-2 in patients with acute coronary syndromes. More trials are needed to confirm their preventive effect.

  7. Differential anti-inflammatory and anti-oxidative effects of dexamethasone and N-acetylcysteine in endotoxin-induced lung inflammation

    PubMed Central

    Rocksén, D; Lilliehöök, B; Larsson, R; Johansson, T; Bucht, A

    2000-01-01

    Inhalation of bacterial endotoxin induces an acute inflammation in the lower respiratory tract. In this study, the anti-inflammatory effects of the anti-oxidant N-acetylcysteine (NAC) and the glucocorticoid dexamethasone were investigated in mice exposed to aerosolized endotoxin (lipopolysaccharide (LPS)). Powerful reduction of neutrophils in bronchoalveolar lavage fluid (BALF) was obtained by a single i.p. injection of dexamethasone (10 mg/kg), whereas treatment with NAC only resulted in reduction of neutrophils when administered at a high dose (500 mg/kg). Measurement of cytokine and chemokine expression in lung tissue revealed a significant decrease of tumour necrosis factor-alpha, IL-1α, IL-1β, IL-6, IL-12p40, and MIP-1α mRNA when mice where treated with dexamethasone but not when treated with NAC. Analysis of oxidative burst demonstrated a remarkable reduction of oxygen radicals in BALF neutrophils after treatment with dexamethasone, whereas the effect of NAC was not significantly different from that in untreated animals. In conclusion, dexamethasone exerted both anti-inflammatory and anti-oxidative effects in acute airway inflammation, probably by blocking early events in the inflammatory cascade. In contrast, treatment with NAC resulted in a weak reduction of the inflammatory response but no inhibition of proinflammatory cytokines or reduction of oxidative burst in neutrophils. These results demonstrate dramatic differences in efficiency and also indicate that the two drugs have different actions. Combined treatment with NAC and dexamethasone revealed an additive action but no synergy was observed. PMID:11091282

  8. The function of tumour necrosis factor and receptors in models of multi-organ inflammation, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease

    PubMed Central

    Kollias, G.; Douni, E.; Kassiotis, G.; Kontoyiannis, D.

    1999-01-01

    There is now good evidence to demonstrate that aberrations in tumour necrosis factor (TNF) production in vivo may be either pathogenic or protective and several plausible mechanisms may explain these contrasting activities. According to the classic pro-inflammatory scenario, failure to regulate the production of TNF at a site of immunological injury may lead to chronic activation of innate immune cells and to chronic inflammatory responses, which may consequently lead to organ specific inflammatory pathology and tissue damage. However, more cryptic functions of this molecule may be considered to play a significant part in the development of TNF mediated pathologies. Direct interference of TNF with the differentiation, proliferation or death of specific pathogenic cell targets may be an alternative mechanism for disease initiation or progression. In addition to these activities, there is now considerable evidence to suggest that TNF may also directly promote or down regulate the adaptive immune response. A more complete understanding of the temporal and spatial context of TNF/TNF receptor (TNF-R) function and of the molecular and cellular pathways leading to the development of TNF/TNF-R mediated pathologies is necessary to fully comprehend relevant mechanisms of disease induction and progression in humans. In this paper, the potential pathogenic mechanisms exerted by TNF and receptors in models of multi-organ inflammation, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease are discussed. Elucidating the nature and level of contribution of these mechanisms in chronic inflammation and autoimmunity may lead to better regulatory and therapeutic applications.

 PMID:10577971

  9. SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines.

    PubMed

    Je, In-Gyu; Kim, Hui-Hun; Park, Pil-Hoon; Kwon, Taeg Kyu; Seo, Seung-Yong; Shin, Tae-Yong; Kim, Sang-Hyun

    2015-05-01

    In this study, we investigated the effect of 3,4,5-trihydroxy-N-(8-hydroxyquinolin-2-yl)benzamide) (SG-HQ2), a synthetic analogue of gallic acid (3,4,5-trihydroxybenzoic acid), on the mast cell-mediated allergic inflammation and the possible mechanism of action. Mast cells play major roles in immunoglobulin E-mediated allergic responses by the release of histamine, lipid-derived mediators, and pro-inflammatory cytokines. We previously reported the potential effects of gallic acid using allergic inflammation models. For incremental research, we synthesized the SG-HQ2 by the modification of functional groups from gallic acid. SG-HQ2 attenuated histamine release by the reduction of intracellular calcium in human mast cells and primary peritoneal mast cells. The inhibitory efficacy of SG-HQ2 was similar with gallic acid. Enhanced expression of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, interleukin-4, and interleukin-6 in activated mast cells was significantly diminished by SG-HQ2 100 times lower concentration of gallic acid. This inhibitory effect was mediated by the reduction of nuclear factor-κB. In animal models, SG-HQ2 inhibited compound 48/80-induced serum histamine release and immunoglobulin E-mediated local allergic reaction, passive cutaneous anaphylaxis. Our results indicate that SG-HQ2, an analogue of gallic acid, might be a possible therapeutic candidate for mast cell-mediated allergic inflammatory diseases through suppression of histamine release and pro-inflammatory cytokines.

  10. Lunasin attenuates obesity-related inflammation in RAW264.7 cells and 3T3-L1 adipocytes by inhibiting inflammatory cytokine production

    PubMed Central

    Chou, Mei-Jia; Wang, Chih-Hsuan

    2017-01-01

    Obesity has become a major threat to public health and is accompanied by chronic low-grade inflammation, which leads to various pathological developments. Lunasin, a natural seed peptide, exhibits several biological activities, such as anti-carcinogenesis, anti-inflammatory, and antioxidant activities. However, the mechanism of action of lunasin in obesity-related inflammation has not been investigated. The aim of this study was to explore whether lunasin could reduce the inflammation induced by obesity-related mediators in RAW264.7 cells and 3T3-L1 adipocytes and whether it could attenuate the crosstalk between the two cell lines. RAW264.7 cells were cultured in leptin-containing medium, adipocyte-conditioned medium (Ad-CM), or co-cultured with 3T3-L1 cells to mimic the physiology of obesity. The data showed that the secretion of pro-inflammatory cytokine interleukin-1β (IL-1β) was inhibited by lunasin after leptin activation of RAW264.7 cells. In addition, lunasin decreased monocyte chemoattractant protein-1 (MCP-1) and IL-1β secretions in the Ad-CM model. Cytokine MCP-1, IL-6, tumor necrosis factor (TNF)-α, and IL-1β secretions were significantly decreased by leptin or Ad-CM plus lipopolysaccharide stimulation. Subsequently, the co-culture of the two cells refined the direct relation between them, resulting in apparently increased MCP-1, and decreased IL-6 levels after lunasin treatment. In 3T3-L1 adipocytes, lunasin also exhibited anti-inflammatory property by inhibiting MCP-1, plasminogen activator inhibitor-1, and leptin productions stimulated by (TNF)-α, lipopolysaccharide, or RAW264.7 cell-conditioned medium. This result revealed that lunasin acts as a potential anti-inflammatory agent not only in macrophages but also in adipocytes, disrupting the crosstalk between these two cells. Therefore, this study suggests the intake of lunasin from diet or as a supplement, for auxiliary prevention or therapy in obesity-related inflammatory applications. PMID

  11. Anti-proliferative and anti-inflammatory effects of 3β,6β,16β-Trihydroxylup-20(29)-ene on cutaneous inflammation.

    PubMed

    Horinouchi, Cintia Delai da Silva; Mendes, Daniel Augusto Gasparin Bueno; Nolte, Stefanie; Brito, Priscilla Salles de; Soley, Bruna da Silva; Favero, Giovani Marino; Facundo, Valdir Alves; Santos, Adair Roberto Soares; Cabrini, Daniela de Almeida; Otuki, Michel Fleith

    2017-01-04

    3β,6β,16β-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders. In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line. Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects. Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Oral administration of d-limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet supplementation in humans.

    PubMed

    d'Alessio, Patrizia A; Ostan, Rita; Bisson, Jean-François; Schulzke, Joerg D; Ursini, Matilde V; Béné, Marie C

    2013-07-10

    To further explore the anti-inflammatory properties of d-Limonene. A rat model was used to compare evolution of TNBS (2,5,6-trinitrobenzene sulfonic acid)-induced colitis after oral feeding with d-Limonene compared to ibuprofen. Peripheral levels of TNF-α (Tumor Necrosis Factor alpha) were assessed in all animals. Cell cultures of fibroblasts and enterocytes were used to test the effect of d-Limonene respectively on TNFα-induced NF-κB (nuclear factor-kappa B) translocation and epithelial resistance. Finally, plasmatic inflammatory markers were examined in an observational study of diet supplementation with d-Limonene-containing orange peel extract (OPE) in humans. Administered per os at a dose of 10mg/kg p.o., d-Limonene induced a significant reduction of intestinal inflammatory scores, comparable to that induced by ibuprofen. Moreover, d-Limonene-fed rats had significantly lowered serum concentrations of TNF-α compared to untreated TNBS-colitis rats. The anti-inflammatory effect of d-Limonene also involved inhibition of TNFα-induced NF-κB translocation in fibroblast cultures. The application of d-Limonene on colonic HT-29/B6 cell monolayers increased epithelial resistance. Finally, inflammatory markers, especially peripheral IL-6, markedly decreased upon OPE supplementation of elderly healthy subjects submitted or not to 56 days of dietary supplementation with OPE. In conclusion, d-Limonene indeed demonstrates significant anti-inflammatory effects both in vivo and in vitro. Protective effects on the epithelial barrier and decreased cytokines are involved, suggesting a beneficial role of d-Limonene as diet supplement in reducing inflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Lymphocyte 'homing' and chronic inflammation.

    PubMed

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  14. Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

    PubMed

    Frieler, Ryan A; Nadimpalli, Sameera; Boland, Lauren K; Xie, Angela; Kooistra, Laura J; Song, Jianrui; Chung, Yutein; Cho, Kae W; Lumeng, Carey N; Wang, Michael M; Mortensen, Richard M

    2015-10-22

    Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models.

  15. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

    PubMed Central

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender

    2016-01-01

    Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

  16. Ocular Penetration and Anti-inflammatory Activity of Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-Induced Inflammation

    PubMed Central

    Galindo, Danielle; Villanueva, Linda; Nguyen, Cathy; Patel, Milan; Borbridge, Lisa; Attar, Mayssa; Schiffman, Rhett M.; Hollander, David A.

    2011-01-01

    Abstract Purpose Anti-inflammatory activity of topical nonsteroidal anti-inflammatory drugs is mediated by suppression of cyclooxygenase (COX) isoenzymes. This study compared ocular penetration and inflammation suppression of topical ketorolac 0.45% and bromfenac 0.09% ophthalmic solutions in a rabbit model. Methods At hour 0, 36 rabbits received ketorolac 0.45%, bromfenac 0.09%, or an artificial tear 3 times once every 20 min. Half of the rabbits in each group then received intravenous injections of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)–dextran at hour 1, and the other half at hour 10. Aqueous and iris-ciliary body (ICB) samples were collected in the former group at hour 2 (peak) and in the latter group at hour 11 (trough) An additional group of 6 animals received only FITC-dextran, and samples were collected 1 h later. Peak and trough nonsteroidal anti-inflammatory drug concentrations were compared with previously determined half-maximal inhibitory concentrations (IC50) for COX isoenzymes. Results Peak and trough aqueous and ICB concentrations of ketorolac were at least 7-fold or greater than those of bromfenac. At peak levels, both ketorolac 0.45% and bromfenac 0.09% significantly inhibited LPS-induced aqueous prostaglandin E2 and FITC-dextran elevation (P < 0.01). At trough, both study drugs significantly inhibited LPS-induced aqueous prostaglandin E2 elevation (P < 0.05), but only ketorolac 0.45% significantly reduced LPS-induced aqueous FITC-dextran elevation (P < 0.01). Aqueous and ICB ketorolac concentrations exceeded its IC50 for COX-1 and COX-2 at peak and trough. Aqueous and ICB bromfenac levels exceeded its IC50 for COX-2 at peak and trough, but not for COX-1 at trough aqueous levels and peak and trough ICB levels. Conclusions Both ketorolac 0.45% and bromfenac 0.09% effectively suppressed inflammation at peak. At trough, only ketorolac 0.45% effectively suppressed inflammation as measured by FITC

  17. The anti-inflammatory limb of the immune response in preterm labor, intra-amniotic infection/inflammation, and spontaneous parturition at term: a role for interleukin-10.

    PubMed

    Gotsch, Francesca; Romero, Roberto; Kusanovic, Juan Pedro; Erez, Offer; Espinoza, Jimmy; Kim, Chong Jai; Vaisbuch, Edi; Than, Nandor Gabor; Mazaki-Tovi, Shali; Chaiworapongsa, Tinnakorn; Mazor, Moshe; Yoon, Bo Hyun; Edwin, Samuel; Gomez, Ricardo; Mittal, Pooja; Hassan, Sonia S; Sharma, Surendra

    2008-08-01

    The anti-inflammatory limb of the immune response is crucial for dampening inflammation. Spontaneous parturition at term and preterm labor (PTL) are mediated by inflammation in the cervix, membranes, and myometrium. This study focuses on the changes in the amniotic fluid concentrations of the anti-inflammatory cytokine interleukin (IL)- 10. The objectives of this study were to determine whether there is a relationship between amniotic fluid concentrations of IL-10 and gestational age, parturition (at term and preterm), and intra-amniotic infection/inflammation (IAI). A cross-sectional study was conducted including 301 pregnant women in the following groups: (1) mid-trimester of pregnancy who delivered at term (n = 112); (2) mid-trimester who delivered preterm neonates (n = 30); (3) term not in labor without IAI (n = 40); (4) term in labor without IAI (n = 24); (5) term in labor with IAI (n = 20); (6) PTL without IAI who delivered at term (n = 31); (7) PTL without IAI who delivered preterm (n = 30); (8) PTL with IAI who delivered preterm (n = 14). IL-10 concentrations in amniotic fluid were determined by a specific and sensitive immunoassay. Non-parametric statistics were used for analysis. (1) IL-10 was detectable in amniotic fluid and its median concentration did not change with gestational age from mid-trimester to term. (2) Patients in labor at term had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term not in labor (p = 0.04). (3) Women at term in labor with IAI had a significantly higher median amniotic fluid IL-10 concentration than that of patients at term in labor without IAI (p = 0.02). (4) Women with PTL and IAI who delivered preterm had a significantly higher median amniotic fluid concentration of IL-10 than those without IAI who delivered preterm and than those who delivered at term (p = 0.009 and p < 0.001, respectively). (5) Among patients with preterm labor without IAI, those who delivered preterm had a

  18. Immunomodulatory and anti-inflammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inflammation in rats.

    PubMed

    Pragasam, Samuel Joshua; Venkatesan, Vijayalakshmi; Rasool, MahaboobKhan

    2013-02-01

    In this study, p-coumaric acid was evaluated for its immunomodulatory and anti-inflammatory properties in vivo. The immunomodulatory effect of p-coumaric acid (100 mg/kg body weight) was assessed by evaluating its effect on cell-mediated immune responses (delayed type hypersensitivity reaction), serum immunoglobulin levels, and macrophage phagocytic index in rats. The anti-inflammatory effects of p-coumaric acid (100 mg/kg body weight) were investigated by examining its effect on expression of tumor necrosis factor (TNF-α) in synovial tissue by immunofluorescence confocal microscopy and circulating immune complexes in serum of adjuvant-induced arthritic rats. The increased cell-mediated immune responses and macrophage phagocytic index observed in control rats were significantly reduced (p < 0.05) upon treatment with p-coumaric acid implying its immunosuppressive property, whereas serum immunoglobulin levels were found to be increased in p-coumaric acid treated control rats. p-coumaric acid also showed significant (p < 0.05) anti-inflammatory effects in adjuvant-induced arthritic rats by effecting a decrease in the expression of inflammatory mediator TNF-α and circulating immune complexes. Indomethacin was used as a reference drug for anti-inflammatory studies. Thus, our results show that p-coumaric acid could be considered a potential immunosuppressive agent in treating autoimmune inflammatory diseases like rheumatoid arthritis.

  19. Dietary antioxidant and anti-inflammatory intake modifies the effect of cadmium exposure on markers of systemic inflammation and oxidative stress.

    PubMed

    Colacino, Justin A; Arthur, Anna E; Ferguson, Kelly K; Rozek, Laura S

    2014-05-01

    Chronic cadmium exposure may cause disease through induction of systemic oxidative stress and inflammation. Factors that mitigate cadmium toxicity and could serve as interventions in exposed populations have not been well characterized. We used data from the 2003-2010 National Health and Nutrition Examination Survey to quantify diet׳s role in modifying associations between cadmium exposure and oxidative stress and inflammation. We created a composite antioxidant and anti-inflammatory diet score (ADS) by ranking participants by quintile of intake across a panel of 19 nutrients. We identified associations and effect modification between ADS, urinary cadmium, and markers of oxidative stress and inflammation by multiple linear regression. An interquartile range increase in urinary cadmium was associated with a 47.5%, 8.8%, and 3.7% increase in C-reactive protein (CRP), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP), respectively. An interquartile range increase in ADS was associated with an 7.4%, 3.3%, 5.2%, and 2.5% decrease in CRP, GGT, ALP, and total white blood cell count respectively, and a 3.0% increase in serum bilirubin. ADS significantly attenuated the association between cadmium exposure, CRP and ALP. Dietary interventions may provide a route to reduce the impact of cadmium toxicity on the population level. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Evaluation of flunixin meglumine pour-on administration on prostaglandin E2 concentration in inflammatory exudate after induction of inflammation in cattle.

    PubMed

    Thiry, Julien; Fournier, René; Roy, Olivier; Catala, Mathias

    2017-04-20

    The effect of flunixin transdermal pour-on solution (Finadyne® Transdermal; MSD Animal Health) on prostaglandin E2 (PGE2) synthesis in bovine inflammatory exudate was evaluated in a tissue cage model of acute inflammation. Twelve calves were randomly allocated to two-treatment groups over two sequences. Three weeks prior to the first period, sterile hollow perforated polyethylene balls were surgically embedded in the subcutis at four distinct sites in each animal. On the first day of each period, an aseptic inflammation was induced by injecting 0.5mL of a 2% carrageenan solution into the lumen of each tissue cage. Treatment with either flunixin transdermal or negative control (NaCl) immediately followed. 0.5mL of exudate was collected prior to challenge, and at 2, 4, 8, 12, 24, 36 and 48h after challenge. Exudate PGE2 concentrations were analyzed using ultra-high pressure liquid chromatography coupled with tandem mass spectrometry method. Mean PGE2 concentrations were consistently lower in calves treated with flunixin transdermal than those measured in calves treated with negative control, indicating an inhibitory activity on cyclooxygenase. Inhibition was the highest at 8h after treatment, and differences with the negative control were significant at +8, 24, 36 and 48h. The flunixin transdermal formulation was effective in reducing PGE2 concentrations in bovine exudate following an induced inflammation. Its anti-inflammatory action started in the first hours after treatment and lasted up to 48h. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Archaic artifacts resembling celestial spheres

    NASA Astrophysics Data System (ADS)

    Dimitrakoudis, S.; Papaspyrou, P.; Petoussis, V.; Moussas, X.

    We present several bronze artifacts from the Archaic Age in Greece (750-480 BC) that resemble celestial spheres or forms of other astronomical significance. They are studied in the context of the Dark Age transition from Mycenaean Age astronomical themes to the philosophical and practical revival of astronomy in the Classical Age with its plethora of astronomical devices. These artifacts, mostly votive in nature are spherical in shape and appear in a variety of forms their most striking characteristic being the depiction of meridians and/or an equator. Most of those artifacts come from Thessaly, and more specifically from the temple of Itonia Athena at Philia, a religious center of pan-Hellenic significance. Celestial spheres, similar in form to the small artifacts presented in this study, could be used to measure latitudes, or estimate the time at a known place, and were thus very useful in navigation.

  2. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

    PubMed

    Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

    2014-06-01

    Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

  3. Anti-inflammatory effects of essential oils extracted from Chamaecyparis obtusa on murine models of inflammation and RAW 264.7 cells.

    PubMed

    Park, Yujin; Yoo, Seung-Ah; Kim, Wan-Uk; Cho, Chul-Soo; Woo, Jong-Min; Yoon, Chong-Hyeon

    2016-04-01

    Antimicrobial, antifungal and anti-inflammatory effects of essential oils extracted from Chamaecyparis obtusa (EOCO) have previously been reported. In the present study, the anti-inflammatory effects of EOCO were investigated in two murine models of inflammation: Carrageenan-induced paw edema and thioglycollate-induced peritonitis, and in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The expression levels of proinflammatory cytokines were analyzed by ELISA, the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by western blotting, and nitrite concentration was measured using Griess reagent. In mice with carrageenan-induced edema, paw thickness and the expression levels of interleukin (IL)‑1β and IL-6 in paw homogenates were significantly decreased in the EOCO (5 and 10 mg/kg) group, as compared with the control group. In mice with thioglycollate-induced peritonitis, treatment with EOCO (5 and 10 mg/kg) reduced the number of total cells and suppressed tumor necrosis factor‑α (TNF‑α), IL‑1β and IL‑6 levels in peritoneal fluid. In addition, EOCO reduced nitric oxide, TNF‑α and IL‑6 production, and suppressed iNOS and COX‑2 expression in LPS‑stimulated RAW 264.7 cells. These results suggest that EOCO may exert anti‑inflammatory effects in vivo and in vitro, and that these effects may be associated with the inhibition of inflammatory mediators. Therefore, EOCO may be considered an effective therapeutic agent for the treatment of inflammatory diseases.

  4. The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells.

    PubMed

    Murphy, Fiona A; Schinwald, Anja; Poland, Craig A; Donaldson, Ken

    2012-04-03

    Carbon nanotubes (CNT) are high aspect ratio nanoparticles with diameters in the nanometre range but lengths extending up to hundreds of microns. The structural similarities between CNT and asbestos have raised concern that they may pose a similar inhalation hazard. Recently CNT have been shown to elicit a length-dependent, asbestos-like inflammatory response in the pleural cavity of mice, where long fibres caused inflammation but short fibres did not. However the cellular mechanisms governing this response have yet to be elucidated. This study examined the in vitro effects of a range of CNT for their ability to stimulate the release of the acute phase cytokines; IL-1β, TNFα, IL-6 and the chemokine, IL-8 from both Met5a mesothelial cells and THP-1 macrophages. Results showed that direct exposure to CNT resulted in significant cytokine release from the macrophages but not mesothelial cells. This pro-inflammatory response was length dependent but modest and was shown to be a result of frustrated phagocytosis. Furthermore the indirect actions of the CNT were examined by treating the mesothelial cells with conditioned media from CNT-treated macrophages. This resulted in a dramatic amplification of the cytokine release from the mesothelial cells, a response which could be attenuated by inhibition of phagocytosis during the initial macrophage CNT treatments. We therefore hypothesise that long fibres elicit an inflammatory response in the pleural cavity via frustrated phagocytosis in pleural macrophages. The activated macrophages then stimulate an amplified pro-inflammatory cytokine response from the adjacent pleural mesothelial cells. This mechanism for producing a pro-inflammatory environment in the pleural space exposed to long CNT has implications for the general understanding of fibre-related pleural disease and design of safe nanofibres.

  5. AMPA/kainate glutamate receptors contribute to inflammation, degeneration and pain related behaviour in inflammatory stages of arthritis

    PubMed Central

    Bonnet, Cleo S; Williams, Anwen S; Gilbert, Sophie J; Harvey, Ann K; Evans, Bronwen A; Mason, Deborah J

    2015-01-01

    Objectives Synovial fluid glutamate concentrations increase in arthritis. Activation of kainate (KA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors (GluRs) increase interleukin-6 (IL-6) release and cause arthritic pain, respectively. We hypothesised that AMPA and KA GluRs are expressed in human arthritis, and that intra-articular NBQX (AMPA/KA GluR antagonist) prevents pain and pathology in antigen-induced arthritis (AIA). Methods GluR immunohistochemistry was related to synovial inflammation and degradation in osteoarthritis (OA) and rheumatoid arthritis (RA). A single intra-articular NBQX injection was given at induction, and knee swelling and gait of AIA and AIA+NBQX rats compared over 21 days, before imaging, RT-qPCR, histology and immunohistochemistry of joints. Effects of NBQX on human primary osteoblast (HOB) activity were determined. Results AMPAR2 and KA1 immunolocalised to remodelling bone, cartilage and synovial cells in human OA and RA, and rat AIA. All arthritic tissues showed degradation and synovial inflammation. NBQX reduced GluR abundance, knee swelling (p<0.001, days 1–21), gait abnormalities (days 1–2), end-stage joint destruction (p<0.001), synovial inflammation (p<0.001), and messenger RNA expression of meniscal IL-6 (p<0.05) and whole joint cathepsin K (p<0.01). X-ray and MRI revealed fewer cartilage and bone erosions, and less inflammation after NBQX treatment. NBQX reduced HOB number and prevented mineralisation. Conclusions AMPA/KA GluRs are expressed in human OA and RA, and in AIA, where a single intra-articular injection of NBQX reduced swelling by 33%, and inflammation and degeneration scores by 34% and 27%, respectively, exceeding the efficacy of approved drugs in the same model. AMPA/KA GluR antagonists represent a potential treatment for arthritis. PMID:24130267

  6. The Biochemical Origin of Pain – Proposing a new law of Pain: The origin of all Pain is Inflammation and the Inflammatory Response PART 1 of 3 – A unifying law of pain

    PubMed Central

    2009-01-01

    We are proposing a unifying theory or law of pain, which states: The origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. Treatment of pain syndromes should be based on these principles: Determination of the inflammatory profile of the pain syndromeInhibition or suppression of production of the appropriate inflammatory mediators e.g. with inflammatory mediator blockers or surgical intervention where appropriateInhibition or suppression of neuronal afferent and efferent (motor) transmission e.g. with anti-seizure drugs or local anesthetic blocksModulation of neuronal transmission e.g. with opioid medication At the L.A. Pain Clinic, we have successfully treated a variety of pain syndromes by utilizing these principles. This theory of the biochemical origin of pain is compatible with, inclusive of, and unifies existing theories and knowledge of the mechanism of pain including the gate control theory, and theories of pre-emptive analgesia, windup and central sensitization. PMID:17240081

  7. The biochemical origin of pain--proposing a new law of pain: the origin of all pain is inflammation and the inflammatory response. Part 1 of 3--a unifying law of pain.

    PubMed

    Omoigui, Sota

    2007-01-01

    We are proposing a unifying theory or law of pain, which states: the origin of all pain is inflammation and the inflammatory response. The biochemical mediators of inflammation include cytokines, neuropeptides, growth factors and neurotransmitters. Irrespective of the type of pain whether it is acute or chronic pain, peripheral or central pain, nociceptive or neuropathic pain, the underlying origin is inflammation and the inflammatory response. Activation of pain receptors, transmission and modulation of pain signals, neuro plasticity and central sensitization are all one continuum of inflammation and the inflammatory response. Irrespective of the characteristic of the pain, whether it is sharp, dull, aching, burning, stabbing, numbing or tingling, all pain arise from inflammation and the inflammatory response. We are proposing a re-classification and treatment of pain syndromes based upon their inflammatory profile. Treatment of pain syndromes should be based on these principles: 1. Determination of the inflammatory profile of the pain syndrome; 2. Inhibition or suppression of production of the appropriate inflammatory mediators, e.g. with inflammatory mediator blockers or surgical intervention where appropriate; 3. Inhibition or suppression of neuronal afferent and efferent (motor) transmission, e.g. with anti-seizure drugs or local anesthetic blocks; 4. Modulation of neuronal transmission, e.g. with opioid medication. At the L.A. Pain Clinic, we have successfully treated a variety of pain syndromes by utilizing these principles. This theory of the biochemical origin of pain is compatible with, inclusive of, and unifies existing theories and knowledge of the mechanism of pain including the gate control theory, and theories of pre-emptive analgesia, windup and central sensitization.

  8. Analgesic effect of percutaneously absorbed non-steroidal anti-inflammatory drugs: an experimental study in a rat acute inflammation model

    PubMed Central

    Sekiguchi, Miho; Shirasaka, Masayoshi; Konno, Shin-ichi; Kikuchi, Shin-ichi

    2008-01-01

    Background External medication that is absorbed percutaneously may be used to reduce inflammation and relieve pain from acute injuries such as ankle sprains and bruises. The plaster method of percutaneous absorption for non-steroidal anti-inflammatory drugs (NSAIDs) was established in Japan in 1988. However, due to the possibility of a placebo effect, the efficacy of this method remains unclear. This experimental study was conducted to control for the placebo effect and to study the efficacy of the plaster method in relieving pain by using a rat model of inflammation. Methods Male Wistar-Imamichi rats were used. A yeast suspension was injected into the right hind paw to induce inflammation. A sheet (2.0 × 1.75 cm) containing the drug was adhered to the inflamed paw. Five treatment groups were used, and each sheet contained a single drug: loxoprofen sodium (loxoprofen-Na) (2.5 mg); felbinac (1.75 mg); indomethacin (1.75 mg); ketoprofen (0.75 mg); or base only (control, 0 mg). Mechanical pain threshold, expression of c-Fos in the dorsal horn, and amount of prostaglandin (PG) E2 in the inflamed paw were evaluated. Results Pain threshold increased after treatment, and was significantly increased in the loxoprofen-Na group compared with the control group (p < 0.05). Amounts of PGE2 were significantly decreased in the loxoprofen-Na and indomethacin groups compared with the control group (p < 0.05). Expression of c-Fos was significantly decreased in the loxoprofen-Na group compared with the control group (p < 0.05). Conclusion Percutaneously absorbed NSAIDs have an analgesic effect, inhibit expression of c-Fos in the dorsal horn, and reduce PGE2 in inflamed tissue, indicating the efficacy of this method of administration for acute inflammation and localized pain. PMID:18234123

  9. Molecular Modeling of Lectin-Like Protein from Acacia farnesiana Reveals a Possible Anti-Inflammatory Mechanism in Carrageenan-Induced Inflammation

    PubMed Central

    Abrantes, Vanessa Erika Ferreira; Matias da Rocha, Bruno Anderson; Batista da Nóbrega, Raphael; Silva-Filho, José Caetano; Teixeira, Claudener Souza; Cavada, Benildo Sousa; Gadelha, Carlos Alberto de Almeida; Ferreira, Sergio Henrique; Figueiredo, Jozi Godoy; Santi-Gadelha, Tatiane; Delatorre, Plinio

    2013-01-01

    Acacia farnesiana lectin-like protein (AFAL) is a chitin-binding protein and has been classified as phytohaemagglutinin from Phaseolus vulgaris (PHA). Legume lectins are examples for structural studies, and this family of proteins shows a remarkable conservation in primary, secondary, and tertiary structures. Lectins have ability to reduce the effects of inflammation caused by phlogistic agents, such as carrageenan (CGN). This paper explains the anti-inflammatory activity of AFAL through structural comparison with anti-inflammatory legume lectins. The AFAL model was obtained by molecular modeling and molecular docking with glycan and carrageenan were performed to explain the AFAL structural behavior and biological activity. Pisum sativum lectin was the best template for molecular modeling. The AFAL structure model is folded as a β sandwich. The model differs from template in loop regions, number of β strands and carbohydrate-binding site. Carrageenan and glycan bind to different sites on AFAL. The ability of AFAL binding to carrageenan can be explained by absence of the sixth β-strand (posterior β sheets) and two β strands in frontal region. AFAL can inhibit pathway inflammatory process by carrageenan injection by connecting to it and preventing its entry into the cell and triggers the reaction. PMID:24490151

  10. Molecular modeling of lectin-like protein from Acacia farnesiana reveals a possible anti-inflammatory mechanism in Carrageenan-induced inflammation.

    PubMed

    Abrantes, Vanessa Erika Ferreira; Matias da Rocha, Bruno Anderson; Batista da Nóbrega, Raphael; Silva-Filho, José Caetano; Teixeira, Claudener Souza; Cavada, Benildo Sousa; Gadelha, Carlos Alberto de Almeida; Ferreira, Sergio Henrique; Figueiredo, Jozi Godoy; Santi-Gadelha, Tatiane; Delatorre, Plinio

    2013-01-01

    Acacia farnesiana lectin-like protein (AFAL) is a chitin-binding protein and has been classified as phytohaemagglutinin from Phaseolus vulgaris (PHA). Legume lectins are examples for structural studies, and this family of proteins shows a remarkable conservation in primary, secondary, and tertiary structures. Lectins have ability to reduce the effects of inflammation caused by phlogistic agents, such as carrageenan (CGN). This paper explains the anti-inflammatory activity of AFAL through structural comparison with anti-inflammatory legume lectins. The AFAL model was obtained by molecular modeling and molecular docking with glycan and carrageenan were performed to explain the AFAL structural behavior and biological activity. Pisum sativum lectin was the best template for molecular modeling. The AFAL structure model is folded as a β sandwich. The model differs from template in loop regions, number of β strands and carbohydrate-binding site. Carrageenan and glycan bind to different sites on AFAL. The ability of AFAL binding to carrageenan can be explained by absence of the sixth β -strand (posterior β sheets) and two β strands in frontal region. AFAL can inhibit pathway inflammatory process by carrageenan injection by connecting to it and preventing its entry into the cell and triggers the reaction.

  11. Salidroside Regulates Inflammatory Response in Raw 264.7 Macrophages via TLR4/TAK1 and Ameliorates Inflammation in Alcohol Binge Drinking-Induced Liver Injury.

    PubMed

    Sun, Peng; Song, Shun-Zong; Jiang, Shuang; Li, Xia; Yao, You-Li; Wu, Yan-Ling; Lian, Li-Hua; Nan, Ji-Xing

    2016-11-09

    The current study was designed to investigate the anti-inflammatory effect of salidroside (SDS) and the underlying mechanism by using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro and a mouse model of binge drinking-induced liver injury in vivo. SDS downregulated protein expression of toll-like receptor 4 (TLR4) and CD14. SDS inhibited LPS-triggered phosphorylation of LPS-activated kinase 1 (TAK1), p38, c-Jun terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Degradation of IκB-α and nuclear translocation of nuclear factor (NF)-κB were effectively blocked by SDS. SDS concentration-dependently suppressed LPS mediated inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein levels, as well as their downstream products, NO. SDS significantly inhibited protein secretion and mRNA expression of of interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Additionally C57BL/6 mice were orally administrated SDS for continuous 5 days, followed by three gavages of ethanol every 30 min. Alcohol binge drinking caused the increasing of hepatic lipid accumulation and serum transaminases levels. SDS pretreatment significantly alleviated liver inflammatory changes and serum transaminases levels. Further investigation indicated that SDS markedly decreased protein level of IL-1β in serum. Taken together, these data implied that SDS inhibits liver inflammation both in vitro and in vivo, and may be a promising candidate for the treatment of inflammatory liver injury.

  12. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation.

    PubMed

    Macedo, E M A; Santos, W C; Sousa, B P; Lopes, E M; Piauilino, C A; Cunha, F V M; Sousa, D P; Oliveira, F A; Almeida, F R C

    2016-06-20

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association.

  13. Association of terpinolene and diclofenac presents antinociceptive and anti-inflammatory synergistic effects in a model of chronic inflammation

    PubMed Central

    Macedo, E.M.A.; Santos, W.C.; Sousa, B.P.; Lopes, E.M.; Piauilino, C.A.; Cunha, F.V.M.; Sousa, D.P.; Oliveira, F.A.; Almeida, F.R.C.

    2016-01-01

    Pharmacological treatment of inflammatory pain is usually done by administration of non-steroidal anti-inflammatory drugs (NSAIDs). These drugs present high efficacy, although side effects are common, especially gastrointestinal lesions. One of the pharmacological strategies to minimize such effects is the combination of drugs and natural products with synergistic analgesic effect. The monoterpene terpinolene (TPL) is a chemical constituent of essential oils present in many plant species, which have pharmacological activities, such as analgesic and anti-inflammatory. The association of ineffective doses of TPL and diclofenac (DCF) (3.125 and 1.25 mg/kg po, respectively) presented antinociceptive and anti-inflammatory effects in the acute (0, 1, 2, 3, 4, 5 and 6 h, after treatment) and chronic (10 days) inflammatory hyperalgesia induced by Freund's complete adjuvant (CFA) in the right hind paw of female Wistar rats (170-230 g, n=6-8). The mechanical hyperalgesia was assessed by the Randall Selitto paw pressure test, which determines the paw withdrawal thresholds. The development of edema was quantified by measuring the volume of the hind paw by plethismography. The TPL/DCF association reduced neutrophils, macrophages and lymphocytes in the histological analysis of the paw, following a standard staining protocol with hematoxylin and eosin and the counts were performed with the aid of optical microscopy after chronic oral administration of these drugs. Moreover, the TPL/DCF association did not induce macroscopic gastric lesions. A possible mechanism of action of the analgesic effect is the involvement of 5-HT2A serotonin receptors, because ketanserin completely reversed the antinociceptive effect of the TPL/DCF association. These results suggest that the TPL/DCF association had a synergistic anti-inflammatory and analgesic effect without causing apparent gastric injury, and that the serotonergic system may be involved in the antinociceptive effect of this association

  14. The Study of Anti-Inflammatory Activity of Oil-Based Dill (Anethum graveolens L.) Extract Used Topically in Formalin-Induced Inflammation Male Rat Paw

    PubMed Central

    Naseri, Mohsen; Mojab, Faraz; Khodadoost, Mahmood; Kamalinejad, Mohammad; Davati, Ali; Choopani, Rasol; Hasheminejad, Abbas; Bararpoor, Zahra; Shariatpanahi, Shamsa; Emtiazy, Majid

    2012-01-01

    Inflammation is one of the symptoms of many common and harmful diseases. As it is incurable through chemical drugs, the study on this ailment using new methods and drugs seems necessary. In addition, the adverse effects of the present anti-inflammatory drugs like NSAIDS and Glucocorticoid appeared in the long time use make such study more demanded. Accordingly, in this study we examined the effects of aerial organs’ extract and seed of a plant commonly used in Iranian traditional medicine named Dill on the inflammation caused by plantar injection of formalin in rats and compared them with Diclofenac-gel. One of the methods used for the inflammation assessment is injecting formalin in the rat paw and then measuring the paw volume by the new plethysmometer (weighing method). The assessment is done at a specific time on day for 8 days and then recorded. This study includes 3 groups of 6 male rats: Formalin, Dill-Oil and Diclofenac-gel groups. The Dill-Oil group received 2 g of Dill-Oil, containing 100 mg Dill-extract and the Diclofenac group received 2 g gel containing, 20 mg Diclofenac Na. Data were analyzed with SPSS 17 using ANOVA, Kruskal-Wallis, and Repeated-Measures. The average paw volumes changes in these groups after Formalin-induced inflammation on 1st day, were 0.31 (standard error (SEM) = 0.02), 0.30 (SEM = 0.01) and 0.32 (SEM = 0.05) respectively, with no significant difference. Regarding the peak of inflammation on the 2nd day, it was indicated that the average inflammations in Formalin, Dill-Oil and Diclofenac-gel groups were 0.44 (SEM = 0.03), 0.15 (SEM = 0.04) and 0.36 (SEM = 0.08), respectively. The paw volume changes in groups receiving Dill-oil and Diclofenac-gel, after the daily formalin injection in 8 days compared to the blank group, had a significant decrease (p < 0.001). The Dill group showed even more decrease in the paw volume compared to the Diclofenac one. The results of paw volume measurement analyzed by the Plethysmometer manifest that

  15. The Study of Anti-Inflammatory Activity of Oil-Based Dill (Anethum graveolens L.) Extract Used Topically in Formalin-Induced Inflammation Male Rat Paw.

    PubMed

    Naseri, Mohsen; Mojab, Faraz; Khodadoost, Mahmood; Kamalinejad, Mohammad; Davati, Ali; Choopani, Rasol; Hasheminejad, Abbas; Bararpoor, Zahra; Shariatpanahi, Shamsa; Emtiazy, Majid

    2012-01-01

    Inflammation is one of the symptoms of many common and harmful diseases. As it is incurable through chemical drugs, the study on this ailment using new methods and drugs seems necessary. In addition, the adverse effects of the present anti-inflammatory drugs like NSAIDS and Glucocorticoid appeared in the long time use make such study more demanded. Accordingly, in this study we examined the effects of aerial organs' extract and seed of a plant commonly used in Iranian traditional medicine named Dill on the inflammation caused by plantar injection of formalin in rats and compared them with Diclofenac-gel. One of the methods used for the inflammation assessment is injecting formalin in the rat paw and then measuring the paw volume by the new plethysmometer (weighing method). The assessment is done at a specific time on day for 8 days and then recorded. This study includes 3 groups of 6 male rats: Formalin, Dill-Oil and Diclofenac-gel groups. The Dill-Oil group received 2 g of Dill-Oil, containing 100 mg Dill-extract and the Diclofenac group received 2 g gel containing, 20 mg Diclofenac Na. Data were analyzed with SPSS 17 using ANOVA, Kruskal-Wallis, and Repeated-Measures. The average paw volumes changes in these groups after Formalin-induced inflammation on 1st day, were 0.31 (standard error (SEM) = 0.02), 0.30 (SEM = 0.01) and 0.32 (SEM = 0.05) respectively, with no significant difference. Regarding the peak of inflammation on the 2nd day, it was indicated that the average inflammations in Formalin, Dill-Oil and Diclofenac-gel groups were 0.44 (SEM = 0.03), 0.15 (SEM = 0.04) and 0.36 (SEM = 0.08), respectively. The paw volume changes in groups receiving Dill-oil and Diclofenac-gel, after the daily formalin injection in 8 days compared to the blank group, had a significant decrease (p < 0.001). The Dill group showed even more decrease in the paw volume compared to the Diclofenac one. The results of paw volume measurement analyzed by the Plethysmometer manifest that

  16. [Recent development of non-steroidal anti-inflammatory drugs on the neuro-inflammation of Alzheimer's disease].

    PubMed

    Ma, Xiao-Wei; Li, Jin-Ze; Zhang, Tian-Tai; Du, Guan-Hua

    2014-09-01

    Neuropathological, clinical epidemiology and animal models studies provide clear evidence for the activation of neuroinflammation in Alzheimer's disease (AD), and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked with reduced risk to develop the disease. But the clinical trials got a negative outcome with traditional NSAIDs treating AD. The therapeutic effects of NSAIDs on Alzheimer's disease are still not clear based on the present research. Profound study for anti-inflammatory mechanisms and standardized clinical trials are needed. As cause and effect relationships between neuroinflammation and AD are being worked out, the challenge is how to realize the effect of traditional NSAIDs on treating AD.

  17. Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice.

    PubMed

    Seleme, Maria C; Kosmac, Kate; Jonjic, Stipan; Britt, William J

    2017-04-15

    mouse model that recapitulates characteristics of the brain infection described in human infants, we have shown that TNF-α plays a key role in brain inflammation, including recruitment of inflammatory mononuclear cells. Neutralization of TNF-α normalized neurodevelopmental abnormalities in infected mice, providing evidence that virus-induced inflammation is a major component of disease in the developing brain. These results suggest that interventions limiting inflammation associated with the infection could potentially improve the neurologic outcome of infants infected in utero with HCMV.

  18. Protective role of surface Toll-like receptor 9 expressing neutrophils in local inflammation during systemic inflammatory response syndrome in mice.

    PubMed

    Meng, Xiuping; Sun, Wei; Ren, Yunjia; Xiao, Yue; Zhao, Peiyan; Lu, Wenting; Hua, Li; Wang, Luowei; Wang, Liying; Yu, Yongli

    2017-10-01

    Clinically, systemic inflammatory response syndrome (SIRS) occurs after serious trauma or sepsis. In sepsis, neutrophils are the major effector cells responsible for eliminating pathogens. However, the role of neutrophils in development of SIRS, especially in local inflammatory area, is controversial. In this study, we established a SIRS mouse model characterized with cytokine-mediated lethal shock by intraperitoneal injection of oligodexynucleotides containing CpG motifs (CpG ODN) in D-galactosamine (D-GalN) sensitized mice based on our previous work and found that abundant neutrophils were rapidly recruited into the peritoneal cavity, where some neutrophils expressed surface TLR9 (sTLR9), defined as sTLR9(+) neutrophils. Along with the progression of SIRS, the expression of sTLR9 in sTLR9(+) neutrophils isolated from peritoneal lavage cells (PLCs) was declined in accompany with an increase in the level of the inflammatory cytokine TNFα and a decrease in the level of the anti-inflammatory cytokine IL-10 in Ly6G(+) PLCs. When using CCT ODN, an oligodeoxynucleotide with CCT repeats, which we have previously shown to be capable of rescuing mice from lethal shock, the expression of sTLR9 on neutrophils was significantly elevated. Adoptive therapy using early recruited neutrophil-rich PLCs containing sTLR9(+) neutrophils that express high levels of sTLR9, could rescue mice from SIRS. Overall, the data reveal that the early recruited sTLR9(+) neutrophils may, at least in the area of local inflammation, play a protective role during SIRS development and provide a method to rescue the patients with severe SIRS via the up-regulation of sTLR9 levels on the surface of neutrophils or via adoptive therapy with protective sub-populations of neutrophils. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation.

    PubMed

    Nardi, Geisson Marcos; Farias Januario, Adriana Graziele; Freire, Cassio Geremia; Megiolaro, Fernanda; Schneider, Kétlin; Perazzoli, Marlene Raimunda Andreola; Do Nascimento, Scheley Raap; Gon, Ana Cristina; Mariano, Luísa Nathália Bolda; Wagner, Glauber; Niero, Rivaldo; Locatelli, Claudriana

    2016-03-01

    Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this study were the investigation and comparison of chemical composition

  20. Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation

    PubMed Central

    Nardi, Geisson Marcos; Farias Januario, Adriana Graziele; Freire, Cassio Geremia; Megiolaro, Fernanda; Schneider, Kétlin; Perazzoli, Marlene Raimunda Andreola; Do Nascimento, Scheley Raap; Gon, Ana Cristina; Mariano, Luísa Nathália Bolda; Wagner, Glauber; Niero, Rivaldo; Locatelli, Claudriana

    2016-01-01

    Background: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. Objective: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Materials and Methods: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. Results: High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. Conclusion: These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. SUMMARY Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this

  1. RETRACTED: Efficacy and Safety of Induction Dosing of Vedolizumab for Reducing Biliary Inflammation in Primary Sclerosing Cholangitis (Psc) in Individuals with Inflammatory Bowel Disease.

    PubMed

    Eksteen, B; Heatherington, J; Oshiomogo, J; Panaccione, R; Kaplan, G; Ghosh, S

    2016-01-01

    This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The abstract authors and presenters of PS124 - EFFICACY AND SAFETY OF INDUCTION DOSING OF VEDOLIZUMAB FOR REDUCING BILIARY INFLAMMATION IN PRIMARY SCLEROSING CHOLANGITIS (PSC) IN INDIVIDUALS WITH INFLAMMATORY BOWEL DISEASE submitted and presented at ILC 2016 have raised concerns that the source data in some cases are inconsistent and requires further evaluation to determine the true magnitude of effect. Hence given the potential impact of this study in PSC at the authors request this abstract, until such time the data can be more completely presented in manuscript form, is being retracted. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

  2. Evidence of different mediators of central inflammation in dysfunctional and inflammatory pain — Interleukin-8 in fibromyalgia and interleukin-1 β in rheumatoid arthritis

    PubMed Central

    Kosek, Eva; Altawil, Reem; Kadetoff, Diana; Finn, Anja; Westman, Marie; Le Maître, Erwan; Andersson, Magnus; Jensen-Urstad, Mats; Lampa, Jon

    2015-01-01

    The purpose of this study was to relate central inflammation to autonomic activity (heart rate variability (HRV)) in patients with rheumatoid arthritis (RA) and fibromyalgia (FM). RA patients had reduced parasympathetic activity and FM patients had increased sympathetic activity compared to healthy controls. Comparisons between RA and FM showed higher cerebrospinal fluid (CSF) interleukin (IL)-1β inversely correlated to parasympathetic activity in RA. The FM patients had higher concentrations of CSF IL-8, IL-1Ra, IL-4 and IL-10, but none of these cytokines correlated with HRV. In conclusion, we found different profiles of central cytokines, i.e., elevated IL-1β in inflammatory pain (RA) and elevated IL-8 in dysfunctional pain (FM). PMID:25773155

  3. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: the normal gut microbiota in health and disease.

    PubMed

    Bäckhed, F

    2010-04-01

    Mammals are metagenomic, in that they are composed not only of their own genome but also those of all of their associated microbes (microbiome). Individual variations in the microbiome influence host health and may be implicated in disease aetiology. Therefore, it is not surprising that decreased microbial diversity is associated with both obesity and inflammatory bowel disease. Studies in germ-free mice have demonstrated that the gut microbiota is required for development of diet-induced obesity as well as inflammatory diseases. However, the underlying molecular mechanism(s) for how the gut microbiota causes metabolic diseases is only beginning to be clarified. Furthermore, emerging data suggest that the gut microbiota may predispose or protect against other important diseases such as cardiovascular disease and diabetes.

  4. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw.

    PubMed

    Costa, Barbara; Colleoni, Mariapia; Conti, Silvia; Parolaro, Daniela; Franke, Chiara; Trovato, Anna Elisa; Giagnoni, Gabriella

    2004-03-01

    Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.1 ml carrageenan (1% w/v in saline) in the rat. At the end of the treatment prostaglandin E2 (PGE2) was assayed in the plasma, and cyclooxygenase (COX) activity, production of nitric oxide (NO; nitrite/nitrate content), and of other oxygen-derived free radicals (malondialdehyde) in inflamed paw tissues. All these markers were significantly increased following carrageenan. Thermal hyperalgesia, induced by carrageenan and assessed by the plantar test, lasted 7 h. Cannabidiol had a time- and dose-dependent anti-hyperalgesic effect after a single injection. Edema following carrageenan peaked at 3 h and lasted 72 h; a single dose of cannabidiol reduced edema in a dose-dependent fashion and subsequent daily doses caused further time- and dose-related reductions. There were decreases in PGE2 plasma levels, tissue COX activity, production of oxygen-derived free radicals, and NO after three doses of cannabidiol. The effect on NO seemed to depend on a lower expression of the endothelial isoform of NO synthase. In conclusion, oral cannabidiol has a beneficial action on two symptoms of established inflammation: edema and hyperalgesia.

  5. Anti-inflammatory effects of Tat-Annexin protein on ovalbumin-induced airway inflammation in a mouse model of asthma

    SciTech Connect

    Lee, Sun Hwa; Kim, Dae Won; Kim, Hye Ri; Woo, Su Jung; Kim, So Mi; Jo, Hyo Sang; Jeon, Seong Gyu; Cho, Sung-Woo; Park, Jong Hoon; Won, Moo Ho; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

    2012-01-20

    Highlights: Black-Right-Pointing-Pointer We construct a cell permeable Tat-ANX1 fusion protein. Black-Right-Pointing-Pointer We examined the protective effects of Tat-ANX1 protein on OVA-induced asthma in animal models. Black-Right-Pointing-Pointer Transduced Tat-ANX1 protein protects from the OVA-induced production of cytokines and eosinophils in BAL fluid. Black-Right-Pointing-Pointer Tat-ANX1 protein markedly reduced OVA-induced MAPK in lung tissues. Black-Right-Pointing-Pointer Tat-ANX1 protein could be useful as a therapeutic agent for lung disorders including asthma. -- Abstract: Chronic airway inflammation is a key feature of bronchial asthma. Annexin-1 (ANX1) is an anti-inflammatory protein that is an important modulator and plays a key role in inflammation. Although the precise action of ANX1 remains unclear, it has emerged as a potential drug target for inflammatory diseases such as asthma. To examine the protective effects of ANX1 protein on ovalbumin (OVA)-induced asthma in animal models, we used a cell-permeable Tat-ANX1 protein. Mice sensitized and challenged with OVA antigen had an increased amount of cytokines and eosinophils in their bronchoalveolar lavage (BAL) fluid. However, administration of Tat-ANX1 protein before OVA challenge significantly decreased the levels of cytokines (interleukin (IL)-4, IL-5, and IL-13) and BAL fluid in lung tissues. Furthermore, OVA significantly increased the activation of mitogen-activated protein kinase (MAPK) in lung tissues, whereas Tat-ANX1 protein markedly reduced phosphorylation of MAPKs such as extracellular signal-regulated protein kinase, p38, and stress-activated protein kinase/c-Jun N-terminal kinase. These results suggest that transduced Tat-ANX1 protein may be a potential protein therapeutic agent for the treatment of lung disorders including asthma.

  6. ApoE deficiency promotes colon inflammation and enhances the inflammatory potential of oxidized-LDL and TNF-α in primary colon epithelial cells

    PubMed Central

    El-Bahrawy, Ali H.; Tarhuni, Abdelmetalab; Kim, Hogyoung; Subramaniam, Venkat; Benslimane, Ilyes; Elmajeed, Zakaria Y. Abd; Okpechi, Samuel C.; Ghonim, Mohamed A.; Hemeida, Ramadan A.M.; Abo-yousef, Amira M.; El-Sherbiny, Gamal A.; Abdel-Raheem, Ihab T.; Kim, Jong; Naura, Amarjit S.; Boulares, A. Hamid

    2016-01-01

    Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homoeostasis remains unknown. ApoE appears to control inflammation by regulating nuclear factor-κB (NF-κB). The present study was designed to examine whether ApoE deficiency affects factors of colon integrity in vivo and given the likelihood that ApoE deficiency increases oxidized lipids and TNF-α, the present study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α in colon epithelial cells (CECs), in vitro. Here we show that ApoE deficiency is associated with chronic inflammation systemically and in colonic tissues as assessed by TNF-α levels. Increased colon TNF-α mRNA coincided with a substantial increase in cyclooxygenase (COX)-2. ApoE deficiency enhanced the potential of oxLDL and TNF-α to induce COX-2 expression as well as several other inflammatory factors in primary CECs. Interestingly, oxLDL enhanced TGF-β expression only in ApoE−/−, but not in wild-type, epithelial cells. ApoE deficiency appears to promote COX-2 expression enhancement through a mechanism that involves persistent NF-κB nuclear localization and PI3 and p38 MAP kinases but independently of Src. In mice, ApoE deficiency promoted a moderate increase in crypt length, which was associated with opposing effects of an increase in cell proliferation and apoptosis at the bottom and top of the crypt respectively. Our results support the notion that ApoE plays a central role in colon homoeostasis and that ApoE deficiency may constitute a risk factor for colon pathologies. PMID:27538678

  7. Uric Acid Is Associated With Inflammatory Biomarkers and Induces Inflammation Via Activating the NF-κB Signaling Pathway in HepG2 Cells.

    PubMed

    Spiga, Rosangela; Marini, Maria Adelaide; Mancuso, Elettra; Di Fatta, Concetta; Fuoco, Anastasia; Perticone, Francesco; Andreozzi, Francesco; Mannino, Gaia Chiara; Sesti, Giorgio

    2017-06-01

    Serum uric acid (UA) has been associated with increased risk of cardiovascular and metabolic diseases. However, the causal mechanisms linking elevated UA levels to cardio-metabolic diseases are still unsettled. One potential explanation for how UA might contribute to cardio-metabolic disease might be its ability to induce systemic inflammation. Herein, we report a positive relationship between serum UA and acute-phase reactants, such as high-sensitivity C-reactive protein, fibrinogen, ferritin, complement C3, and erythrocyte sedimentation rate, in a cohort of 2731 nondiabetic adults. The relationship remains significant after adjustment for several confounders, including age, sex, adiposity, anti-hypertensive treatments or diuretics use. To confirm the existence of a causal relationship, we examined the effect of UA on the expression of inflammatory biomarkers in human hepatoma HepG2 cells and characterized the signaling pathway by which UA acts. We show that UA stimulates the expression of C-reactive protein, fibrinogen, ferritin, and complement C3 in a dose-dependent fashion. The proinflammatory effects of UA were abrogated by benzbromarone, a specific inhibitor of UA transporters. Exposure of cells to UA resulted in activation of the IκB kinase/IκBα/NF-κB signaling pathway that was attenuated by benzbromarone. The effect of UA was completely blocked by the antioxidant N-acetylcysteine. These in vivo and in vitro data suggest that hyperuricemia might induce the expression of hepatic inflammatory molecules by activating the proinflammatory NF-κB signaling cascade. Because inflammation has an important pathogenetic role in metabolic and cardiovascular disease, our study may help understanding the mechanism by which hyperuricemia may contribute to organ damage. © 2017 American Heart Association, Inc.

  8. Anti-inflammatory effect of sugar-amino acid Maillard reaction products on intestinal inflammation model in vitro and in vivo.

    PubMed

    Oh, Jun-Gu; Chun, Su-Hyun; Kim, Da Hyun; Kim, Jin Hye; Shin, Hye Soo; Cho, Yong Soo; Kim, Yong Ki; Choi, Hee-Don; Lee, Kwang-Won

    2017-09-08

    The Maillard reaction is a nonenzymatic reaction between an amino acid and a reducing sugar that usually occurs upon heating. This reaction occurs routinely in cooking, generates numerous products, which are collectively referred to as Maillard reaction products (MRPs) contributing to aroma and color features. Advanced glycation end-products (AGEs) transformed from MRPs are participated in many types of inflammation reaction. In this study, various sugar-amino acid MRPs were prepared from three different amino acids (lysine, arginine, and glycine) and sugars (glucose, fructose, and galactose) for 1 h with heating at 121 °C. Treatment of lipopolysaccharide-stimulated RAW264.7 macrophages with the MRPs decreased nitric oxide (NO) expression compared to control without MRPs treatment. MRPs derived from lysine and galactose (Lys-Gal MRPs) significantly inhibited NO expression. The retentate fraction of Lys-Gal MRPs with cut-off of molecular weight of 3-10 kDa (LGCM) suppressed NO expression more effectively than did Lys-Gal MRPs. The anti-inflammatory effect of LGCM was evaluated using a co-culture system consisting of Caco-2 (apical side) and RAW264.7 or THP-1 (basolateral side) cells to investigate the gut inflammation reaction by stimulated macrophage cells. In this system, LGCM prevented a decreased transepithelial electrical resistance, and decreased both tumor necrosis factor-α production in macrophages and interleukin (IL)-8 and IL-1β mRNA expression in Caco-2 cells. In co-culture and in vivo dextran sulfate sodium (DSS)-induced colitis model study, we also observed the anti-inflammatory activity of LGCM. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Endothelial FoxM1 Mediates Bone Marrow Progenitor Cell-Induced Vascular Repair and Resolution of Inflammation following Inflammatory Lung Injury

    PubMed Central

    Zhao, Yidan D.; Huang, Xiaojia; Yi, Fan; Dai, Zhiyu; Qian, Zhijian; Tiruppathi, Chinnaswamy; Tran, Khiem; Zhao, You-Yang

    2015-01-01

    Adult stem cell treatment is a potential novel therapeutic approach for acute respiratory distress syndrome. Given the extremely low rate of cell engraftment, it is believed that these cells exert their beneficial effects via paracrine mechanisms. However, the endogenous mediator(s) in the pulmonary vasculature remains unclear. Employing the mouse model with endothelial cell (EC)-restricted disruption of FoxM1 (FoxM1 CKO), here we show that endothelial expression of the reparative transcriptional factor FoxM1 is required for the protective effects of bone marrow progenitor cells (BMPC) against LPS-induced inflammatory lung injury and mortality. BMPC treatment resulted in rapid induction of FoxM1 expression in WT but not FoxM1 CKO lungs. BMPC-induced inhibition of lung vascular injury, resolution of lung inflammation, and survival, as seen in WT mice, were abrogated in FoxM1 CKO mice following LPS challenge. Mechanistically, BMPC treatment failed to induce lung EC proliferation in FoxM1 CKO mice, which was associated with impaired expression of FoxM1 target genes essential for cell cycle progression. We also observed that BMPC treatment enhanced endothelial barrier function in WT, but not in FoxM1-deficient EC monolayers. Restoration of β-catenin expression in FoxM1-deficient ECs normalized endothelial barrier enhancement in response to BMPC treatment. These data demonstrate the requisite role of endothelial FoxM1 in the mechanism of BMPC-induced vascular repair to restore vascular integrity and accelerate resolution of inflammation, thereby promoting survival following inflammatory lung injury. PMID:24578354

  10. Suppression of Transglutaminase-2 is Involved in Anti-Inflammatory Actions of Glucosamine in 12-O-Tetradecanoylphorbol-13-Acetate-Induced Skin Inflammation

    PubMed Central

    Cho, Sun A; Lee, Hye Ja; Lee, Eun Ji; Kang, June Hee; Kim, You Lee; Kim, Hyun Ji; Oh, Seung Hyun; Choi, Changsun; Lee, Ho; Kim, Soo Youl

    2012-01-01

    Glucosamine (GS) is well known for the treatment of inflam-mation. However, the mechanism and efficacy of GS for skin inflammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxy-genase-2 (COX-2), NF-κB and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the inflamed ear of mice and anti-inflammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema. PMID:24009824

  11. The Role of Chlamydia trachomatis Polymorphic Membrane Proteins in Inflammation and Sequelae among Women with Pelvic Inflammatory Disease

    PubMed Central

    Taylor, Brandie D.; Darville, Toni; Tan, Chun; Bavoil, Patrik M.; Ness, Roberta B.; Haggerty, Catherine L.

    2011-01-01

    Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis. PMID:22028586

  12. The role of Chlamydia trachomatis polymorphic membrane proteins in inflammation and sequelae among women with pelvic inflammatory disease.

    PubMed

    Taylor, Brandie D; Darville, Toni; Tan, Chun; Bavoil, Patrik M; Ness, Roberta B; Haggerty, Catherine L

    2011-01-01

    Chlamydia trachomatis polymorphic membrane proteins (Pmps) may increase genital tract inflammation and play a role in virulence. Antibody levels for PmpA, PmpD, and PmpI, measured in densitometric units, were assessed among a pilot sample of 40 C. trachomatis-infected women with mild-to-moderate clinical PID. Women who expressed antibodies to PmpA were less likely to achieve pregnancy (40.0% versus 85.7%; P = 0.042) and less likely to have a live birth (0.0% versus 80.0%; P = 0.005) compared to women who did not express antibody to PmpA. Women who expressed antibodies to PmpI were more likely to have upper genital tract infection (61.5% versus 20.0%; P = 0.026). However, seropositivity to PmpI and PmpD did not modify the risk of reproductive sequelae or inflammation. Seropositivity to chlamydial PmpA may represent a biomarker of increased risk of sequelae secondary to infection with C. trachomatis.

  13. NS6180, a new KCa3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease

    PubMed Central

    Strøbæk, D; Brown, DT; Jenkins, DP; Chen, Y-J; Coleman, N; Ando, Y; Chiu, P; Jørgensen, S; Demnitz, J; Wulff, H; Christophersen, P

    2013-01-01

    Background and Purpose The KCa3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of KCa3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses. Experimental Approach We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2H-1,4-benzothiazin-3(4H)-one) with respect to potency and molecular site of action on KCa3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease (IBD). Key Results NS6180 inhibited cloned human KCa3.1 channels (IC50 = 9 nM) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed KCa3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15–20 nM). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed KCa3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg−1 b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg−1 q.d.). Conclusions and Implications NS6180 represents a novel class of KCa3.1 channel inhibitors which inhibited experimental colitis, suggesting KCa3.1 channels as targets for pharmacological control of intestinal inflammation. PMID:22891655

  14. Protective Effect of Bioactivity Guided Fractions of Ziziphus jujuba Mill. Root Bark against Hepatic Injury and Chronic Inflammation via Inhibiting Inflammatory Markers and Oxidative Stress

    PubMed Central

    Kandimalla, Raghuram; Dash, Suvakanta; Kalita, Sanjeeb; Choudhury, Bhaswati; Malampati, Sandeep; Kalita, Kasturi; Kalita, Bhupalee; Devi, Rajlakshmi; Kotoky, Jibon

    2016-01-01

    The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer, and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark (ZJRB) against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF), and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD, and CAT) and cytokine levels (TNF-α, Il-1β, and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of ZJRB as good therapeutic agent for liver toxicity and chronic inflammation. PMID:27656145

  15. Suppression of molecular inflammatory pathways by Toll-like receptor 7, 8, and 9 antagonists in a model of IL-23-induced skin inflammation.

    PubMed

    Suárez-Fariñas, Mayte; Arbeit, Robert; Jiang, Weiwen; Ortenzio, Francesca S; Sullivan, Tim; Krueger, James G

    2013-01-01

    Psoriasis is a complex inflammatory disease resulting from the activation of T helper (Th) 1 and Th17 cells. Recent evidence suggests that abnormal activation of Toll-like receptors (TLRs) 7, 8 and 9 contributes to the initiation and maintenance of psoriasis. We have evaluated the effects of TLR antagonists on the gene expression profile in an IL-23-induced skin inflammation model in mice. Psoriasis-like skin lesions were induced in C57BL/6 mice by intradermal injection of IL-23 in the dorsum. Two TLR antagonists were compared: IMO-3100, an antagonist of TLRs 7 and 9, and IMO-8400, an antagonist of TLRs 7, 8 and 9, both of which previously have been shown to reduce epidermal hyperplasia in this model. Skin gene expression profiles of IL-23-induced inflammation were compared with or without TLR antagonist treatment. IL-23 injection resulted in alteration of 5100 gene probes (fold change ≥ 2, FDR < 0.05) including IL-17 pathways that are up-regulated in psoriasis vulgaris. Targeting TLRs 7, 8 and 9 with IMO-8400 resulted in modulation of more than 2300 mRNAs while targeting TLRs 7 and 9 with IMO-3100 resulted in modulation of more than 1900 mRNAs. Both agents strongly decreased IL-17A expression (>12-fold reduction), normalized IL-17 induced genes such as beta-defensin and CXCL1, and normalized aberrant expression of keratin 16 (indicating epidermal hyperplasia). These results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9 and that these receptors represent novel therapeutic targets in psoriasis vulgaris and other diseases with similar pathophysiology.

  16. Epidermal Nbn deletion causes premature hair loss and a phenotype resembling psoriasiform dermatitis

    PubMed Central

    Seidel, Philipp; Remus, Martina; Delacher, Michael; Grigaravicius, Paulius; Reuss, David E.; Frappart, Lucien; von Deimling, Andreas; Feuerer, Markus; Abdollahi, Amir; Frappart, Pierre-Olivier

    2016-01-01

    Nijmegen Breakage Syndrome is a disease caused by NBN mutations. Here, we report a novel function of Nbn in skin homeostasis. We found that Nbn deficiency in hair follicle (HF) progenitors promoted increased DNA damage signaling, stimulating p16Ink4a up-regulation, Trp53 stabilization and cytokines secretion leading to HF-growth arrest and hair loss. At later stages, the basal keratinocytes layer exhibited also enhanced DNA damage response but in contrast to the one in HF progenitor was not associated with pro-inflammatory cytokines expression, but rather increased proliferation, lack of differentiation and immune response resembling psoriasiform dermatitis. Simultaneous Nbn and Trp53 inactivation significantly exacerbated this phenotype, due to the lack of inhibition of pro-inflammatory cytokines secretion by Trp53. Altogether, we demonstrated novel functions of Nbn in HF maintenance and prevention of skin inflammation and we provide a mechanistic explanation that links cell intrinsic DNA maintenance with large scale morphological tissue alterations. PMID:27050272

  17. S-Propargyl-Cysteine, a Novel Hydrogen Sulfide Donor, Inhibits Inflammatory Hepcidin and Relieves Anemia of Inflammation by Inhibiting IL-6/STAT3 Pathway

    PubMed Central

    Xin, Hong; Zhu, Yi Zhun

    2016-01-01

    Anemia of inflammation (AI) is clinically prevalent and greatly threatens public health. Traditional remedies have raised controversy during clinical practice, calling for alternative therapies. We have recently found that hydrogen sulfide (H2S) inhibits inflammatory hepcidin, the critical mediator of AI. However, due to the chemical property of H2S, there remains an urgent need for a stable H2S donor in AI treatment. Here we reported that S-propargyl-cysteine (SPRC), a novel water-soluble H2S donor, suppressed hepatic hepcidin and corrected hypoferremia induced by lipopolysaccharide. The effects of SPRC were reversed by inhibition of cystathionine γ-lyase, one of the major endogenous H2S synthases. Moreover, SPRC reduced serum hepcidin, improved transferrin saturation, and maintained erythrocyte membrane integrity in a chronic mouse AI model. Consistently, splenomegaly was ameliorated and splenic iron accumulation relieved. Mechanism study indicated that serum IL-6 content and hepatic Il-6 mRNA were decreased by SPRC, in parallel with reduced hepatic JAK2/STAT3 activation. On the whole, our data reveal the inhibition of inflammatory hepcidin by SPRC, and suggest SPRC as a potential remedy against AI. PMID:27649298

  18. A supramolecular topical gel derived from a non-steroidal anti-inflammatory drug, fenoprofen, is capable of treating skin inflammation in mice.

    PubMed

    Majumder, Joydeb; Yedoti, Pavani; Dastidar, Parthasarathi

    2015-02-28

    A new series of bioconjugates derived from a non-steroidal anti-inflammatory drug (NSAID), namely fenoprofen, has been synthesised by amidation with various biogenic molecules such as β-alanine, aminocaproic acid and tyramine with the aim of converting the NSAID into a supramolecular gelator for plausible biomedical applications. One such bioconjugate (2) showed gelation ability with methylsalicylate (MS) and 1% menthol in methyl salicylate (MMS) solvents. These gels were characterized by table top rheology, high resolution-transmission electron microscopy (HR-TEM) and dynamic rheology. Gelator 2 was found to be biostable both in proteolytic enzymes and in blood serum of BALB/c mouse under physiological conditions. It was also found to be biocompatible, as revealed by the methyl thiazolyldiphenyl tetrazolium bromide (MTT) assay in mouse macrophage RAW 264.7 and mouse myoblast C2C12 cells. The anti-inflammatory response (prostaglandin E2 assay, denoted PGE2 assay) of 2 was comparable to that of the parent drug fenoprofen calcium salt. Finally, a topical gel formulation of 2 displayed in vivo self-delivery application in treating imiquimod (IMQ) induced skin inflammation in BALB/c mice.

  19. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

    PubMed

    Fowke, Jay H; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E

    2016-01-01

    BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. The WHR, an estimate of centralized

  20. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms

    PubMed Central

    Fowke, Jay H.; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E.

    2016-01-01

    Background BPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association. Methods Participants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI). Results Prostate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation. Conclusion

  1. Beneficial effects of treatment with transglutaminase inhibitor cystamine on the severity of inflammation in a rat model of inflammatory bowel disease.

    PubMed

    Elli, Luca; Ciulla, Michele M; Busca, Giuseppe; Roncoroni, Leda; Maioli, Claudio; Ferrero, Stefano; Bardella, Maria Teresa; Bonura, Antonella; Paliotti, Roberta; Terrani, Claudia; Braidotti, Paola

    2011-03-01

    Inflammatory bowel disease (IBD) represents a socially and clinically relevant disorder, characterized by intestinal chronic inflammation. Cystamine (CysN) is a multipotent molecule with healthy effects and, moreover, it is an inhibitor of transglutaminases (TGs), including the TG type 2 (TG2), an enzyme with pleiotropic functions, involved in different pathways of inflammation and central in the pathogenesis of some human disorders as the IBD. Our aim was to evaluate the effect of CysN in an IBD rat model. A total of 30 rats were divided into 4 groups: controls without treatment (CTR; n=7); receiving the 2,4,6-trinitrobenzene sulfonic acid enema (TNBS group; n=8); treated with TNBS enema plus oral CysN (TNBS-CysN group; n=8); treated with CysN (CysN group; n=7). After killing, bowel inflammation was evaluated applying specific scores. TG activity, TG2 and isopeptide bond immunohistochemical expression, and tumor necrosis factor-α (TNF-α) were evaluated in the colonic tissue, such as interleukin-6 (IL-6) serological levels (ELISA). TG2 was also evaluated on the luminal side of the colon by immunoautoradiography. Colonic samples from IBD patients were compared with animal results. TNBS-CysN group developed a less severe colitis compared with the TNBS group (macroscopic score 0.43±0.78 vs 3.28±0.95, microscopic score 6.62±12.01 vs 19.25±6.04, P<0.05, respectively) associated with a decrease of TG activity, TG2 and isopeptide bond immunohistochemical expression, TNF-α and IL-6 levels. No statistically significant differences were found between CysN and CTR groups. The colonic immunolocalization of TG2 was comparable in humans affected by IBD and TNBS-administered animals. This is the first demonstration that treatment with a CysN has an anti-inflammatory effect, reducing severity of colitis in a rat model. CysN could be tested as a possible treatment or co-treatment in IBD therapeutic trials.

  2. Defining the therapeutic time window for suppressing the inflammatory prostaglandin E2 signaling after status epilepticus

    PubMed Central

    Du, Yifeng; Kemper, Timothy; Qiu, Jiange; Jiang, Jianxiong

    2016-01-01

    Neuroinflammation is a common feature in nearly all neurological and some psychiatric disorders. Resembling its extraneural counterpart, neuroinflammation can be both beneficial and detrimental depending on the responding molecules. The overall effect of inflammation on disease progression is highly dependent on the extent of inflammatory mediator production and the duration of inflammatory induction. The time-dependent aspect of inflammatory responses suggests that the therapeutic time window for quelling neuroinflammation might vary with molecular targets and injury types. Therefore, it is important to define the therapeutic time window for anti-inflammatory therapeutics, as contradicting or negative results might arise when different treatment regimens are utilized even in similar animal models. Herein, we discuss a few critical factors that can help define the therapeutic time window and optimize treatment paradigm for suppressing the cyclooxygenase-2/prostaglandin-mediated inflammation after status epilepticus. These determinants should also be relevant to other anti-inflammatory therapeutic strategies for the CNS diseases. PMID:26689339

  3. Dietary Enrichment with 20% Fish Oil Decreases Mucus Production and the Inflammatory Response in Mice with Ovalbumin-Induced Allergic Lung Inflammation

    PubMed Central

    Hall, Jean A.; Hartman, Jaye; Skinner, Monica M.; Schwindt, Adam R.; Fischer, Kay A.; Vorachek, William R.; Bobe, Gerd; Valentine, Beth A.

    2016-01-01

    The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks. At 8 and 10 weeks, mice were given an intraperitoneal injection of saline (10 control-fed mice) or OVA (30 remaining mice). Once at 10 weeks and on 3 consecutive days during week 12, mice were challenged by nebulizing with saline or OVA. Mice were euthanized 24 hours after the last challenge and blood was collected for plasma FA analysis. Bronchoalveolar lavage (BAL) fluid was collected to determine cell composition and Th2-type cytokine (IL-4, IL-13) concentrations. Periodic acid-Schiff (PAS) + mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue were quantified using morphometric analysis. Relative abundance of mRNA for mucin (Muc4, Muc5ac, and Muc5b) and Th2-type cytokine (IL-4, IL-5, and IL-13) genes were compared with ß-actin by qPCR. Supplementation with either corn oil or fish oil effectively altered plasma FA profiles towards more (n-6) FA or (n-3) FA, respectively (P < 0.0001). Sensitization and challenge with OVA increased the proportion of neutrophils, lymphocytes, and eosinophils, and decreased the proportion of macrophages and concentrations of IL-13 in BAL fluid; increased the percentage of PAS+ mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue; and increased gene expression of mucins (Muc4, Muc5ac, and Muc5b) and Th2-type cytokines (IL-5 and IL-13) in lung tissue of control-fed mice. Dietary PUFA reversed the increase in PAS+ mucus-producing cells (P = 0.003). In addition, dietary

  4. Dietary Enrichment with 20% Fish Oil Decreases Mucus Production and the Inflammatory Response in Mice with Ovalbumin-Induced Allergic Lung Inflammation.

    PubMed

    Hall, Jean A; Hartman, Jaye; Skinner, Monica M; Schwindt, Adam R; Fischer, Kay A; Vorachek, William R; Bobe, Gerd; Valentine, Beth A

    The prevalence of asthma has increased in recent decades, which may be related to higher dietary intake of (n-6) polyunsaturated fatty acids (PUFA) and lower intake of (n-3) PUFA, e.g., those contained in fish oil. The objective of this study was to determine if dietary PUFA enrichment decreases mucus production or the inflammatory response associated with ovalbumin (OVA)-induced allergic lung inflammation. Mice (n = 10/group) were fed control, 20% fish oil, or 20% corn oil enriched diets for a total of 12 weeks. At 8 and 10 weeks, mice were given an intraperitoneal injection of saline (10 control-fed mice) or OVA (30 remaining mice). Once at 10 weeks and on 3 consecutive days during week 12, mice were challenged by nebulizing with saline or OVA. Mice were euthanized 24 hours after the last challenge and blood was collected for plasma FA analysis. Bronchoalveolar lavage (BAL) fluid was collected to determine cell composition and Th2-type cytokine (IL-4, IL-13) concentrations. Periodic acid-Schiff (PAS) + mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue were quantified using morphometric analysis. Relative abundance of mRNA for mucin (Muc4, Muc5ac, and Muc5b) and Th2-type cytokine (IL-4, IL-5, and IL-13) genes were compared with ß-actin by qPCR. Supplementation with either corn oil or fish oil effectively altered plasma FA profiles towards more (n-6) FA or (n-3) FA, respectively (P < 0.0001). Sensitization and challenge with OVA increased the proportion of neutrophils, lymphocytes, and eosinophils, and decreased the proportion of macrophages and concentrations of IL-13 in BAL fluid; increased the percentage of PAS+ mucus-producing cells and CD45+ inflammatory cell infiltrates in lung tissue; and increased gene expression of mucins (Muc4, Muc5ac, and Muc5b) and Th2-type cytokines (IL-5 and IL-13) in lung tissue of control-fed mice. Dietary PUFA reversed the increase in PAS+ mucus-producing cells (P = 0.003). In addition, dietary

  5. Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.

    PubMed

    Nakao, Tetsushi; Horie, Takahiro; Baba, Osamu; Nishiga, Masataka; Nishino, Tomohiro; Izuhara, Masayasu; Kuwabara, Yasuhide; Nishi, Hitoo; Usami, Shunsuke; Nakazeki, Fumiko; Ide, Yuya; Koyama, Satoshi; Kimura, Masahiro; Sowa, Naoya; Ohno, Satoko; Aoki, Hiroki; Hasagawa, Koji; Sakamoto, Kazuhisa; Minatoya, Kenji; Kimura, Takeshi; Ono, Koh

    2017-09-07

    Abdominal aortic aneurysm (AAA) is an increasingly prevalent and ultimately fatal disease with no effective pharmacological treatment. Because matrix degradation induced by vascular inflammation is the major pathophysiology of AAA, attenuation of this inflammation may improve its outcome. Previous studies suggested that microRNA-33 inhibition and genetic ablation of microRNA-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis. MicroRNA-33a-5p expression in central zone of human AAA was higher than marginal zone. MicroRNA-33 deletion attenuated AAA formation in both mouse models of angiotensin II- and calcium chloride-induced AAA. Reduced macrophage accumulation and monocyte chemotactic protein-1 expression were observed in calcium chloride-induced AAA walls in microRNA-33(-/-) mice. In vitro experiments revealed that peritoneal macrophages from microRNA-33(-/-) mice showed reduced matrix metalloproteinase 9 expression levels via c-Jun N-terminal kinase inactivation. Primary aortic vascular smooth muscle cells from microRNA-33(-/-) mice showed reduced monocyte chemotactic protein-1 expression by p38 mitogen-activated protein kinase attenuation. Both of the inactivation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase were possibly because of the increase of ATP-binding cassette transporter A1 that is a well-known target of microRNA-33. Moreover, high-density lipoprotein cholesterol derived from microRNA-33(-/-) mice reduced expression of matrix metalloproteinase 9 in macrophages and monocyte chemotactic protein-1 in vascular smooth muscle cells. Bone marrow transplantation experiments indicated that microRNA-33-deficient bone marrow cells ameliorated AAA formation in wild-type recipients. MicroRNA-33 deficiency in recipient mice was also shown to contribute the inhibition of AAA formation. These data strongly suggest that inhibition of microRNA-33 will be effective as a novel strategy for treating AAA. © 2017

  6. Riboflavin along with antibiotics balances reactive oxygen species and inflammatory cytokines and controls Staphylococcus aureus infection by boosting murine macrophage function and regulates inflammation.

    PubMed

    Dey, Somrita; Bishayi, Biswadev

    2016-01-01

    Macrophages serve as intracellular reservoirs of S. aureus. Recent in vitro studies have confirmed high level resistance by S. aureus to macrophage mediated killing and the intracellular persistence of Staphylococci may play an important role in the pathogenesis. Since this localization protects them from both cell-mediated and humoral immune responses, therefore, a successful anti-staphylococcal therapy should include the elimination of intracellular bacteria, further protecting the host cells from staphylococci-induced cell death. So, only antibiotic therapy may not be helpful, successful therapy needs combination of drugs not only for elimination of pathogen but also for rescuing the host cell for S. aureus induced cell death. In keeping with this idea an in vitro study has been done to examine the effect of Riboflavin along with antibiotics on phagocytosis, hydorgen peroxide, superoxide production, antioxidant enzyme levels, and cytokine levels in mouse macrophages for amelioration of the Staphylococcus aureus burden. The immune boosting effects of Riboflavin have been validated through perturbations of redox homeostasis and pro-inflammatory cytokines measurements. It was observed that the supplementation of Vitamin B-2 (Riboflavin) not only enhances macrophage function as previously reported but also decreases pro-inflammatory responses in Staphylococcus aureus infected macrophages. The observed influence of Riboflavin on enhanced antimicrobial effects such as enhanced phagocytosis of macrophages exposed to S. aureus, hydrogen peroxide or superoxide production when combined with either ciprofloxacin (CIP) or Azithromycin (AZM) and decrease in pro-inflammatory responses of IFN-γ, IL-6, IL-1β. Riboflavin treatment also decreased NO and TNF-α level possibly by inhibiting the NF-κβ pathway. The increased antioxidant enzymes like glutathione reductase, SOD and GSH level helped in maintaining a stable redox state in the cell. Riboflavin plus antibiotic

  7. Solanum paranense Extracts and Solanine Present Anti-Inflammatory Activity in an Acute Skin Inflammation Model in Mice

    PubMed Central

    Piana, Mariana; Camponogara, Camila

    2017-01-01

    The aim of the study was to evaluate the anti-inflammatory activity of the S. paranense crude extract, S. paranense alkaloid fraction, and solanine alkaloid. These samples reduce the croton oil-induced ear edema in a dose-dependent manner and a maximum inhibition of 81%, 98%, and 80% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Moreover, the samples inhibit the MPO activity with an inhibition maximum of 51%, 40%, and 46% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Similar results were found for dexamethasone 0.10 mg/ear (positive control), which showed inhibitions of ear edema and MPO activity of 100% and 65%, respectively. These results found probably are related to the presence of solanine which is present in significant quantity in the alkaloid fraction and others as rutin and rosmarinic, chlorogenic, and gallic acids. These results support the use of S. paranense for the treatment of inflammatory skin disorders. PMID:28626486

  8. Solanum paranense Extracts and Solanine Present Anti-Inflammatory Activity in an Acute Skin Inflammation Model in Mice.

    PubMed

    Piana, Mariana; Camponogara, Camila; Boligon, Aline Augusti; Oliveira, Sara Marchesan

    2017-01-01

    The aim of the study was to evaluate the anti-inflammatory activity of the S. paranense crude extract, S. paranense alkaloid fraction, and solanine alkaloid. These samples reduce the croton oil-induced ear edema in a dose-dependent manner and a maximum inhibition of 81%, 98%, and 80% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Moreover, the samples inhibit the MPO activity with an inhibition maximum of 51%, 40%, and 46% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Similar results were found for dexamethasone 0.10 mg/ear (positive control), which showed inhibitions of ear edema and MPO activity of 100% and 65%, respectively. These results found probably are related to the presence of solanine which is present in significant quantity in the alkaloid fraction and others as rutin and rosmarinic, chlorogenic, and gallic acids. These results support the use of S. paranense for the treatment of inflammatory skin disorders.

  9. Anti-inflammatory and chondroprotective effects of nutraceuticals from Sasha's Blend in a cartilage explant model of inflammation.

    PubMed

    Pearson, Wendy; Orth, Michael W; Karrow, Niel A; Maclusky, Neil J; Lindinger, Michael I

    2007-08-01

    New Zealand green lipped mussel (NZGLM), abalone (AB), and shark cartilage (SC) are extensively used for treatment of and/or as preventatives for arthritis, despite a relative paucity of scientific evidence for efficacy. This research integrated a simulated digestion protocol with ultrafiltration and cartilage explants to generate new information on the anti-inflammatory and chondroprotective properties of NZGLM, SC, and AB. Each nutraceutical was artificially digested using simulated gastric and intestinal fluids, and the crude digest was ultrafiltered (50 kDa). Each filtrate was applied individually to cartilage explants before the explants were stimulated with IL-1 to induce an acute inflammatory response. Media were collected daily for 48 h and analyzed for prostaglandin E(2) (PGE(2)), glycosaminoglycan (GAG), and nitric oxide (NO), and cartilage tissue was differentially stained to determine the relative proportion of live and dead cells. SC and NZGLM significantly inhibited IL-1-induced PGE(2) synthesis and IL-1-induced GAG release, and AB was an effective inhibitor of IL-1-induced NO production. The three test nutraceuticals affect at least three major pathways involved in the catabolic cycle of arthritis and may prove important treatments and/or preventatives for the pain and degradation associated with this condition. The methodology and results describe a useful model for evaluating dietary nutraceuticals in vitro.

  10. Keratoconus: an inflammatory disorder?

    PubMed Central

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-01-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition. PMID:25931166

  11. Keratoconus: an inflammatory disorder?

    PubMed

    Galvis, V; Sherwin, T; Tello, A; Merayo, J; Barrera, R; Acera, A

    2015-07-01

    Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.

  12. Bioenergetic Dysfunction and Inflammation in Alzheimer’s Disease: A Possible Connection

    PubMed Central

    Wilkins, Heather M.; Carl, Steven M.; Greenlief, Alison C. S.; Festoff, Barry W.; Swerdlow, Russell H.

    2014-01-01

    Inflammation is observed in Alzheimer’s disease (AD) subject brains. Inflammation-relevant genes are increasingly implicated in AD genetic studies, and inflammatory cytokines to some extent even function as peripheral biomarkers. What underlies AD inflammation is unclear, but no “foreign” agent has been implicated. This suggests that internally produced damage-associated molecular pattern (DAMPs) molecules may drive inflammation in AD. A more complete characterization and understanding of AD-relevant DAMPs could advance our understanding of AD and suggest novel therapeutic strategies. In this review, we consider the possibility that mitochondria, intracellular organelles that resemble bacteria in many ways, trigger and maintain chronic inflammation in AD subjects. Data supporting the possible nexus between AD-associated bioenergetic dysfunction are discussed. PMID:25426068

  13. The posterior ligamentous complex inflammatory syndrome: spread of fluid and inflammation in the retrodural space of Okada.

    PubMed

    Lehman, V T; Murthy, N S; Diehn, F E; Verdoorn, J T; Maus, T P

    2015-05-01

    The retrodural space of Okada is situated dorsal to the ligamentum flavum in the interlaminar space, and provides communication between contralateral facet joints. MRI will often demonstrate heterogeneous signal abnormality with contrast enhancement in this space and several communicating compartments of the posterior ligamentous complex: bilateral facet joints, adventitial interspinous bursae, or retrodural cysts penetrating the ligamentum flavum. Pars interarticularis defects are frequently present. This imaging pattern may be associated with axial low back pain and/or radicular pain. Recognition of this pattern at MRI has distinct implications for image interpretation, unifying prior reports of involvement of individual components of the posterior ligamentous complex. Its recognition will also affect planning for therapeutic interventional pain procedures. We refer to this constellation of imaging and clinical findings as posterior ligamentous complex inflammatory syndrome (PLCIS). Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  14. Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice

    SciTech Connect

    Arenas, Meritxell; Gil, Felix B.A.; Gironella, Meritxell; Hernandez, Victor; Jorcano, Sandra; Biete, Albert; Pique, Josep M.; Panes, Julian . E-mail: jpanes@clinic.ub.es

    2006-10-01

    Purpose: The aim of this study was to determine the effects of low-dose radiotherapy (LD-RT) on the inflammatory response and to characterize the potential mechanisms underlying these effects. Methods and Materials: Mice were irradiated with 0.1, 0.3, 0.6 Gy, or sham radiation before lipopolysaccharide (LPS) challenge. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Intercellular adhesion molecule-1 (ICAM-1) expression was determined using radiolabeled antibodies 5 h after irradiation. Production of transforming growth factor-{beta}{sub 1} (TGF-{beta}{sub 1}) was measured by enzyme-linked immunosorbent assay and its in vivo functional relevance by immunoneutralization. Results: Compared with vehicle treated animals, LPS induced a marked increase in leukocyte adhesion (0.13 {+-} 0.59 vs. 5.89 {+-} 1.03, p < 0.0001) in intestinal venules. The number of adherent leukocytes was significantly reduced by the 3 doses of LD-RT tested; the highest inhibition was observed with 0.3 Gy (0.66 {+-} 1.96, p < 0.0001). LPS-induced ICAM-1 upregulation was not modified by LD-RT. Circulating levels of TGF-{beta}{sub 1} were significantly increased in response to LD-RT in controls and LPS challenged animals. Neutralization of TGF-{beta}{sub 1} partially restored LPS-induced adhesion (4.83 {+-} 1.41, p < 0.05). Conclusions: LD-RT has a significant anti-inflammatory effect, inhibiting leukocyte recruitment, which is maximal at 0.3 Gy. This effect results in part from increased TGF-{beta}{sub 1} production and is not related to modulation of ICAM-1 expression.

  15. Aqueous extract from Ipomoea asarifolia (Convolvulaceae) leaves and its phenolic compounds have anti-inflammatory activity in murine models of edema, peritonitis and air-pouch inflammation.

    PubMed

    Furtado, Allanny A; Torres-Rêgo, Manoela; Lima, Maíra C J S; Bitencourt, Mariana A O; Estrela, Andréia Bergamo; Souza da Silva, Nayara; da Silva Siqueira, Emerson Michell; Tomaz, José Carlos; Lopes, Norberto Peporine; Silva-Júnior, Arnóbio Antônio; Zucolotto, Silvana M; Fernandes-Pedrosa, Matheus F

    2016-11-04

    Ipomoea asarifolia (Desr.) Roem. and Schult.(Convolvulaceae), popularly known as salsa or salsa-brava, is a plant of which the decoction of leaves is used in folk medicine to treat various inflammatory disorders such of dermatitis, scabies, symptoms of syphilis, skin ulcers and external wounds. However, little is known about possible compounds and mechanisms of action of the plant to support the activities reported by popular use. The study aimed to identify bioactive molecules present in the crude extract of I. asarifolia leaves and investigate the anti-inflammatory potential of this extract in different experimental in vivo models to improve the understanding on that activity. Aqueous extract of I. asarifolia leaves was prepared by decoction (1:10 m/v) and its chromatographic profile was obtained by high performance liquid chromatography coupled with diode array detector (HPLC-DAD) and liquid chromatography diode array detector coupled with mass spectrometry (LC-DAD-MS). The potential anti-inflammatory activity of the extract was assessed using the following in vivo models: xylene-induced ear edema (20, 30 and 40mg/kg), evaluating the degree of edema formation; carrageenan-induced peritonitis (10, 20 and 30mg/kg), evaluating leukocyte migration and cytokine levels (IL-1β, IL-6, IL-12 and TNF-α) at 4h; zymosan-induced air pouch inflammation (20, 30 and 40mg/kg), evaluating the kinetics of leukocyte migration by total and differential counts at 6, 24 and 48h. The same tests were conducted using pure compounds identified in the aqueous extract from I. asarifolia leaves in different doses for each experimental model. The compounds identified in the aqueous extract of I. asarifolia leaves by HPLC-DAD and LC-DAD-MS were rutin, chlorogenic acid and caffeic acid. The extract significantly reduced ear edema induced by xylene (81%, 85% and 86% for doses of 20, 30 and 40mg/kg, respectively, p<0.001), as well as cell migration in experimental models of peritonitis (70%, 78

  16. Strategies for managing periodontal inflammation.

    PubMed

    Schonfeld, Steven E

    2010-04-01

    Most of the tissue destruction in periodontal disease is caused by the patient's inflammatory response. Classical approaches to controlling inflammation rely on attempts to eliminate pathogenic bacteria that incite the inflammatory response through mechanical or chemical means. This approach still has a place in treating periodontal inflammation today. Emerging and future approaches will rely more on modifying the inflammatory response itself, by limiting the activity of proinflammatory pathways and by amplifying pathways that resolve inflammation.

  17. miRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism

    PubMed Central

    Jin, Xi; Chen, Dong; Zheng, Ruo-Heng; Zhang, Hong; Chen, Yi-Peng; Xiang, Zun

    2017-01-01

    AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-α, IL-1β, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods. RESULTS An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-α, IL-1β, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group. CONCLUSION The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD. PMID:28104982

  18. Inflammation switches the differentiation program of Ly6Chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon

    PubMed Central

    Rivollier, Aymeric; He, Jianping; Kole, Abhisake; Valatas, Vassilis

    2012-01-01

    Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hiCX3CR1hi (CD11b+CD103−) cells account for 80% of mouse colonic lamina propria MHC-IIhi cells. Both CD11c+ and CD11c− cells within this population were identified as MPs based on multiple criteria, including an MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1−CD11b− DCs, CD103+CX3CR1−CD11b+ DCs, and CD103−CX3CR1intCD11b+ DCs. In noninflammatory conditions, Ly6Chi monocytes (MOs) differentiated primarily into CD11c+ but not CD11c− MPs. In contrast, during colitis, Ly6Chi MOs massively invaded the colon and differentiated into proinflammatory CD103−CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS, and TNF. These findings demonstrate the dual capacity of Ly6Chi blood MOs to differentiate into either regulatory MPs or inflammatory DCs in the colon and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions. PMID:22231304

  19. Hypoxia and Mucosal Inflammation

    PubMed Central

    Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

    2016-01-01

    Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

  20. Redox Proteomics of the Inflammatory Secretome Identifies a Common Set of Redoxins and Other Glutathionylated Proteins Released in Inflammation, Influenza Virus Infection and Oxidative Stress

    PubMed Central

    Checconi, Paola; Salzano, Sonia; Bowler, Lucas; Mullen, Lisa; Mengozzi, Manuela; Hanschmann, Eva-Maria; Lillig, Christopher Horst; Sgarbanti, Rossella; Panella, Simona; Nencioni, Lucia; Palamara, Anna Teresa; Ghezzi, Pietro

    2015-01-01

    Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions. PMID:25985305

  1. Relationships between equine airway reactivity measured by flowmetric plethysmography and specific indicators of airway inflammation in horses with suspected inflammatory airway disease.

    PubMed

    Wichtel, M; Gomez, D; Burton, S; Wichtel, J; Hoffman, A

    2016-07-01

    Agreement between airway reactivity measured by flowmetric plethysmography and histamine bronchoprovocation, and lower airway inflammation measured by bronchoalveolar lavage (BAL) cytology, has not been studied in horses with suspected inflammatory airway disease (IAD). We tested the hypothesis that airway reactivity is associated with BAL cytology in horses presenting for unexplained poor performance and/or chronic cough. Prospective clinical study. Forty-five horses, predominantly young Standardbred racehorses, presenting for unexplained poor performance or chronic cough, underwent endoscopic evaluation, tracheal wash, flowmetric plethysmography with histamine bronchoprovocation and BAL. Histamine response was measured by calculating PC35, the concentration of nebulised histamine eliciting an increase in Δflow of 35%. In this population, there was no significant correlation between histamine response and cell populations in BAL cytology. When airway hyperreactivity (AHR) was defined as ≥35% increase in Δflow at a histamine concentration of <6 mg/ml, 24 of the 45 horses (53%) were determined to have AHR. Thirty-three (73%) had either abnormal BAL cytology or AHR, and were diagnosed with IAD on this basis. Of horses diagnosed with IAD, 9 (27%) had an abnormal BAL, 11 (33%) had AHR and 13 (39%) had both. Airway reactivity and BAL cytology did not show concordance in this population of horses presenting for unexplained poor performance and/or chronic cough. Failure to include tests of airway reactivity may lead to underdiagnosis of IAD in young Standardbred racehorses that present with clinical signs suggestive of IAD. © 2015 EVJ Ltd.

  2. Inflammation and haemostasis.

    PubMed

    Margetic, Sandra

    2012-01-01

    Inflammation and haemostasis are interrelated pathophysiologic processes that considerably affect each other. In this bidirectional relationship, inflammation leads to activation of the haemostatic system that in turn also considerably influences inflammatory activity. Such, the haemostatic system acts in concert with the inflammatory cascade creating an inflammation-haemostasis cycle in which each activated process promotes the other and the two systems function in a positive feedback loop. The extensive crosstalk between immune and haemostatic systems occurs at level of all components of the haemostatic system including vascular endothelial cells, platelets, plasma coagulation cascade, physiologic anticoagulants and fibrinolytic activity. During inflammatory response, inflammatory mediators, in particular proinflammatory cytokines, play a central role in the effects on haemostatic system by triggering its disturbance in a number of mechanisms including endothelial cell dysfunction, increased platelet reactivity, activation of the plasma coagulation cascade, impaired function of physiologic anticoagulants and suppressed fibrinolytic activity. The two examples of pathophysiologic processes in which the tight interdependent relationship between inflammation and haemostasis considerably contribute to the pathogenesis and/or progression of disease are systemic inflammatory response to infection or sepsis and acute arterial thrombosis as a consequence of ruptured atherosclerotic plaque. Close links between inflammation and haemostasis help explain the prothrombotic tendency in these two clinical conditions in which inflammation shifts the haemostatic activity towards procoagulant state by the ability of proinflammatory mediators to activate coagulation system and to inhibit anticoagulant and fibrinolytic activities. This review summarizes the current knowledge of the complex interactions in the bidirectional relationship between inflammation and haemostasis.

  3. Hepatocyte growth factor preferentially activates the anti-inflammatory arm of NF-κB signaling to induce A20 and protect renal proximal tubular epithelial cells from inflammation.

    PubMed

    da Silva, Cleide G; Maccariello, Elizabeth R; Wilson, Szuhuei Wu; Putheti, Prabhakar; Daniel, Soizic; Damrauer, Scott M; Peterson, Clayton R; Siracuse, Jeffrey J; Kaczmarek, Elzbieta; Ferran, Christiane

    2012-04-01

    Inflammation induces the NF-κB dependent protein A20 in human renal proximal tubular epithelial cells (RPTEC), which secondarily contains inflammation by shutting down NF-κB activation. We surmised that inducing A20 without engaging the pro-inflammatory arm of NF-κB could improve outcomes in kidney disease. We showed that hepatocyte growth factor (HGF) increases A20 mRNA and protein levels in RPTEC without causing inflammation. Upregulation of A20 by HGF was NF-κB/RelA dependent as it was abolished by overexpressing IκBα or silencing p65/RelA. Unlike TNFα, HGF caused minimal IκBα and p65/RelA phosphorylation, with moderate IκBα degradation. Upstream, HGF led to robust and sustained AKT activation, which was required for p65 phosphorylation and A20 upregulation. While HGF treatment of RPTEC significantly increased A20 mRNA, it failed to induce NF-κB dependent, pro-inflammatory MCP-1, VCAM-1, and ICAM-1 mRNA. This indicates that HGF preferentially upregulates protective (A20) over pro-inflammatory NF-κB dependent genes. Upregulation of A20 supported the anti-inflammatory effects of HGF in RPTEC. HGF pretreatment significantly attenuated TNFα-mediated increase of ICAM-1, a finding partially reversed by silencing A20. In conclusion, this is the first demonstration that HGF activates an AKT-p65/RelA pathway to preferentially induce A20 but not inflammatory molecules. This could be highly desirable in acute and chronic renal injury where A20-based anti-inflammatory therapies are beneficial. Copyright © 2011 Wiley Periodicals, Inc.

  4. Hepatocyte Growth Factor preferentially activates the anti-inflammatory arm of NF-κB signaling to induce A20 and protect renal proximal tubular epithelial cells from inflammation

    PubMed Central

    da Silva, Cleide G.; Maccariello, Elizabeth R.; Wilson, Szuhuei Wu; Putheti, Prabhakar; Daniel, Soizic; Damrauer, Scott M.; Peterson, Clayton; Siracuse, Jeffrey J.; Kaczmarek, Elzbieta; Ferran, Christiane

    2012-01-01

    Inflammation induces the NF-κB dependent protein A20 in human renal proximal tubular epithelial cells (RPTEC), which secondarily contains inflammation by shutting down NF-κB activation. We surmised that inducing A20 without engaging the pro-inflammatory arm of NF-κB could improve outcomes in kidney disease. We showed that hepatocyte growth factor (HGF) increases A20 mRNA and protein levels in RPTEC without causing inflammation. Upregulation of A20 by HGF was NF-κB/RelA dependent as it was abolished by overexpressing IκBα or silencing p65/RelA. Unlike TNFα, HGF caused minimal IκBα and p65/RelA phosphorylation, with moderate IκBα degradation. Upstream, HGF led to robust and sustained AKT activation, which was required for p65 phosphorylation and A20 upregulation. While HGF treatment of RPTEC significantly increased A20 mRNA, it failed to induce NF-κB dependent, pro-inflammatory MCP-1, VCAM-1, and ICAM-1 mRNA. This indicates that HGF preferentially upregulates protective (A20) over pro-inflammatory NF-κB dependent genes. Upregulation of A20 supported the anti-inflammatory effects of HGF in RPTEC. HGF pretreatment significantly attenuated TNFα-mediated increase of ICAM-1, a finding partially reversed by silencing A20. In conclusion, this is the first demonstration that HGF activates an AKT-p65/RelA pathway to preferentially induce A20 but not inflammatory molecules. This could be highly desirable in acute and chronic renal injury where A20-based anti-inflammatory therapies are beneficial. PMID:21618526

  5. Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation.

    PubMed

    Kallaur, Ana Paula; Lopes, Josiane; Oliveira, Sayonara Rangel; Simão, Andrea Name Colado; Reiche, Edna Maria Vissoci; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; de Pereira, Wildea Lice Carvalho Jennings; Alfieri, Daniele Frizon; Borelli, Sueli Donizete; Kaimen-Maciel, Domacio Ramon; Maes, Michael

    2016-10-01

    There is evidence that activated immune-inflammatory and oxidative and nitrosative stress (IO&NS) pathways play a role in the pathophysiology of multiple sclerosis (MS) and depression. This study examines serum levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10; peroxides (LOOH); nitric oxide metabolites (NOx); albumin; ferritin; C-reactive protein (CRP); and tumor necrosis factor (TNF)-β NcoI polymorphism (rs909253) and gadolinium-enhanced magnetic resonance imaging (MRI) scan in MS patients with (n = 42) and without (n = 108) depression and normal controls (n = 249). Depression is scored using the depressive subscale of the Hospital Anxiety and Depression Scale (HADS). The extent of neurological disability is measured using the Expanded Disability Status Scale (EDSS) at the same time of the abovementioned measurements and 5 years earlier. Disease progression is assessed as actual EDSS-EDSS 5 years earlier. Three variables discriminate MS patients with depression from those without depression, i.e., increased IL-6 and lower IL-4 and albumin. Binary logistic regression showed that MS with depression (versus no depression) was characterized by more gastrointestinal symptoms and disease progression, higher serum IL-6, and lower albumin levels. In subjects with MS, the HADS score was significantly predicted by three EDSS symptoms, i.e., pyramidal, gastrointestinal, and visual symptoms. Fifty-eight percent of the variance in the HADS score was predicted by gastrointestinal symptoms, visual symptoms, the TNFB1/B2 genotype, and contrast enhancement (both inversely associated). There were no significant associations between depression in MS and type of MS, duration of illness, age, sex, nicotine dependence, and body mass index. MS with depression is associated with signs of peripheral inflammation, more disability, disease progression, gastrointestinal and visual symptoms, but less contrast enhancement as compared to MS without depression. It is

  6. Vitamin D and inflammation

    PubMed Central

    Cannell, John J; Grant, William B; Holick, Michael F

    2014-01-01

    Several studies found an inverse relationship between 25-hydroxyvitamin D [25(OH)D] and markers of inflammation. A controversy exists as to whether vitamin D lowers inflammation or whether inflammation lowers 25(OH)D concentrations. Certainly 25(OH)D concentrations fall after major surgery. However, is this due to inflammation lowering 25(OH)D or is 25(OH)D being metabolically cleared by the body to quell inflammation. We searched the literature and found 39 randomized controlled trials (RCT) of vitamin D and markers of inflammation. Seventeen found significantly reduced inflammatory markers, 19 did not, one was mixed and one showed adverse results. With few exceptions, studies in normal subjects, obesity, type 2 diabetics, and stable cardiovascular disease did not find significant beneficial effects. However, we found that 6 out of 7 RCTS of vitamin D3 in highly inflammatory conditions (acute infantile congestive heart failure, multiple sclerosis, inflammatory bowel disease, cystic fibrosis, SLE, active TB and evolving myocardial infarction) found significant reductions. We found baseline and final 25(OH)D predicted RCTs with significant reduction in inflammatory markers. Vitamin D tends to modestly lower markers of inflammation in highly inflammatory conditions, when baseline 25(OH)D levels were low and when achieved 25(OH)D levels were higher. Future inquiries should: recruit subjects with low baseline 25(OH)D levels, subjects with elevated markers of inflammation, subjects with inflammatory conditions, achieve adequate final 25(OH)D levels, and use physiological doses of vitamin D. We attempted to identify all extant randomized controlled trials (RCTs) of vitamin D that used inflammatory markers as primary or secondary endpoints. PMID:26413186

  7. Loss of epidermal Evi/Wls results in a phenotype resembling psoriasiform dermatitis.

    PubMed

    Augustin, Iris; Gross, Julia; Baumann, Daniel; Korn, Claudia; Kerr, Grainne; Grigoryan, Tamara; Mauch, Cornelia; Birchmeier, Walter; Boutros, Michael

    2013-08-26

    Cells of the epidermis renew constantly from germinal layer stem cells. Although epithelial cell differentiation has been studied in great detail and the role of Wnt signaling in this process is well described, the contribution of epidermal Wnt secretion in epithelial cell homeostasis remains poorly understood. To analyze the role of Wnt proteins in this process, we created a conditional knockout allele of the Wnt cargo receptor Evi/Gpr177/Wntless and studied mice that lacked Evi expression in the epidermis. We found that K14-Cre, Evi-LOF mice lost their hair during the first hair cycle, showing a reddish skin with impaired skin barrier function. Expression profiling of mutant and wild-type skin revealed up-regulation of inflammation-associated genes. Furthermore, we found that Evi expression in psoriatic skin biopsies is down-regulated, suggesting that Evi-deficient mice developed skin lesions that resemble human psoriasis. Immune cell infiltration was detected in Evi-LOF skin. Interestingly, an age-dependent depletion of dendritic epidermal T cells (DETCs) and an infiltration of γδ(low) T cells in Evi mutant epidermis was observed. Collectively, the described inflammatory skin phenotype in Evi-deficient mice revealed an essential role of Wnt secretion in maintaining normal skin homeostasis by enabling a balanced epidermal-dermal cross talk, which affects immune cell recruitment and DETC survival.

  8. Inflammatory Biomarkers and Atherosclerosis.

    PubMed

    Soeki, Takeshi; Sata, Masataka

    2016-01-01

    Atherosclerosis has been regarded as a form of chronic vascular inflammation. Numerous biomarkers associated with inflammation have been identified as novel targets to monitor atherosclerosis and cardiovascular risk. C-reactive protein (CRP) is one of the most actively studied and established inflammatory biomarkers for cardiovascular events. However, CRP response is triggered by many disorders unrelated to cardiovascular disease, which interferes with the clinical application. This review describes established and traditional inflammatory biomarkers including CRP as well as novel inflammatory biomarkers reflective of local atherosclerotic inflammation. In addition, we focus on the potential usefulness of inflammatory biomarkers in developing anti-atherosclerotic therapeutic approaches.

  9. Studies on the pathogenesis of acute inflammation. I. The inflammatory reaction to thermal injury as observed in the rabbit ear chamber.

    PubMed

    ALLISON, F; SMITH, M R; WOOD, W B

    1955-12-01

    A special adaptation of the rabbit ear chamber has been devised to study in vivo, under high magnification, the acute inflammatory reaction to thermal injury. Systematic observations of the cellular response have led to the following conclusions. 1. Contrary to the commonly accepted view, vasodilatation does not always precede the adherence of leucocytes to vascular endothelium. 2. The fact that leucocytes often adhere to one another as well as to the endothelium indicates that the increased adhesiveness characteristic of the early stages of inflammation is not limited to the surfaces of the endothelial cells. 3. The sharing of erythrocytes and platelets in this increased stickiness suggests that a "plasma factor" is involved. There is indirect but as yet inconclusive evidence that the plasma factor may concern the clotting mechanism of the blood. 4. The adherence of leucocytes to the endothelium is usually first noted on the side of the vessel closest to the site of injury. This previously undescribed phenomenon of "unilateral sticking" is in keeping with the concept that the vascular reaction is caused by products of cellular damage which diffuse to the vessel from the site of injury. 5. Leucocytes always become adherent to the endothelium before penetrating the vessel wall. They often migrate about for some time on the endothelial surface before undergoing diapedesis. 6. Although no definite stomata are at any time visible in the endothelium, penetrating leucocytes may leave behind temporary defects through which other leucocytes and even erythrocytes may pass. 7. The diapedesis of leucocytes appears to depend primarily upon cellular motility. It may occur in static vessels where there is presumably little if any hydrostatic pressure. 8. The diapedesis of erythrocytes, on the other hand, is a passive process depending upon intravascular pressure. Its occurrence is greatly exaggerated in areas in which intravascular pressure becomes elevated. Such elevations

  10. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders

    PubMed Central

    Dudesek, A; Rimmele, F; Tesar, S; Kolbaske, S; Rommer, P S; Benecke, R; Zettl, U K

    2014-01-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement ‘peppering’ the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long

  11. CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders.

    PubMed

    Dudesek, A; Rimmele, F; Tesar, S; Kolbaske, S; Rommer, P S; Benecke, R; Zettl, U K

    2014-03-01

    Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long

  12. PET Imaging of Inflammation Biomarkers

    PubMed Central

    Wu, Chenxi; Li, Fang; Niu, Gang; Chen, Xiaoyuan

    2013-01-01

    Inflammation plays a significant role in many disease processes. Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process. Positron emission tomography using 18F-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm. In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation. This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation. Also, the current attempt in differentiating inflammation from tumor using PET is also discussed. PMID:23843893

  13. Molecular mechanisms of the anti-inflammatory functions of interferons

    PubMed Central

    Kovarik, Pavel; Sauer, Ines; Schaljo, Barbara

    2014-01-01

    Interferons are pleiotropic cytokines with important proinflammatory functions required in defence against infections with bacteria, viruses and multicellular parasites. In recent years, fundamental functions of interferons in other processes such as cancer immunosurveillance, immune homeostasis and immunosuppression have been established. In addition, anti-inflammatory roles of interferons are well-documented in several inflammatory disease models in the mouse, most importantly in experimental autoimmune encephalomyelitis that resembles multiple sclerosis in humans. While the beneficial effects of interferons in such disease models are known, the molecular mechanisms remain poorly understood. Only recently a few molecular principles for the anti-inflammatory properties of interferons at the cellular level have been revealed. They include the ability of interferons to reduce the expression of the receptors for the inflammation-related cytokines IL-1 and IL-4, or to increase the expression of the potent anti-inflammatory genes tristetraprolin and Twist. However, the individual contribution of these anti-inflammatory responses to the overall beneficial effects of interferons in inflammatory diseases is still an open question. Also, the reason for the apparently limited number of tissues that are susceptible to the anti-inflammatory functions of interferons remains enigmatic. This review summarizes the present knowledge of the anti-inflammatory effects of interferons, and describes the currently known molecular mechanisms that may help explain the benefits of interferon signalling in several inflammatory diseases. PMID:18086388

  14. Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators.

    PubMed

    Dhanasekar, Chitra; Rasool, Mahaboobkhan

    2016-09-05

    The anti-inflammatory effect of morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -α, interleukin (IL)-1β, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)), and nuclear factor-kappa B (NF-κB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in morin treated MSU crystal-induced rats. In addition, morin treatment reduced the protein expression of NF-κB p65, p-NF-κB p65, iNOS, COX-2, and TNF-α. The results clearly demonstrated that morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats.

  15. Obesity and Cancer Mechanisms: Tumor Microenvironment and Inflammation.

    PubMed

    Iyengar, Neil M; Gucalp, Ayca; Dannenberg, Andrew J; Hudis, Clifford A

    2016-12-10

    Purpose There is growing evidence that inflammation is a central and reversible mechanism through which obesity promotes cancer risk and progression. Methods We review recent findings regarding obesity-associated alterations in the microenvironment and the local and systemic mechanisms through which these changes support tumor growth. Results Locally, hyperadiposity is associated with altered adipose tissue function, adipocyte death, and chronic low-grade inflammation. Most individuals who are obese harbor inflamed adipose tissue, which resembles chronically injured tissue, with immune cell infiltration and remodeling. Within this distinctly altered local environment, several pathophysiologic changes are found that may promote breast and other cancers. Consistently, adipose tissue inflammation is associated with a worse prognosis in patients with breast and tongue cancers. Systemically, the metabolic syndrome, including dyslipidemia and insulin resistance, occurs in the setting of adipose inflammation and operates in concert with local mechanisms to sustain the inflamed microenvironment and promote tumor growth. Importantly, adipose inflammation and its protumor consequences can be found in some individuals who are not considered to be obese or overweight by body mass index. Conclusion The tumor-promoting effects of obesity occur at the local level via adipose inflammation and associated alterations in the microenvironment, as well as systemically via circulating metabolic and inflammatory mediators associated with adipose inflammation. Accurately characterizing the obese state and identifying patients at increased risk for cancer development and progression will likely require more precise assessments than body mass index alone. Biomarkers of adipose tissue inflammation would help to identify high-risk populations. Moreover, adipose inflammation is a reversible process and represents a novel therapeutic target that warrants further study to break the obesity

  16. Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats.

    PubMed

    Arigesavan, Kaninathan; Sudhandiran, Ganapasam

    2015-05-29

    Chronic inflammation is one of the remarkable etiologic factors for various human ailments including cancer. The well known hypothesis is that persistent inflammation in colon can increase the risk of colorectal cancer (CRC). In this study, a pharmacological evaluation of carvacrol, a phenolic monoterpene constituent of essential oils produced from aromatic plant Oreganum vulgarea sp. on colitis associated colon cancer (CACC) induced by 1,2 Dimethylhydrazine (DMH) and dextran sodium sulfate (DSS) in male Fischer 344 rat model was studied. F344 rats were given three subcutaneous injections of DMH (40 mg/kg body wt) in the first week and were given free access to drinking water containing 1% DSS for the next one week followed by 7-14 days of water as three cycles. Carvacrol was administrated before and after tumor induction at a concentration of 50 mg/kg body weight (o.p). Carvacrol treated groups promotes the endogenous antioxidant system and suppress the inflammation in DMH/DSS induced animals. An increased antioxidant status and restoration of histological lesions in the inflamed colonic mucosa was observed in carvacrol treated rats. This effect was confirmed biochemically by reducing free-radical accumulation and suppressing expression of pro-inflammatory mediators. In this study, Carvacrol significantly increased the anti-oxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) glutathione (GSH) levels and reduced lipid peroxides (LPO), myeloperoxidase (MPO) and nitric oxide (NO) as compared to DMH/DSS induced rats. These dramatic changes facilitate the suppression of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), and interleukin-1 beta (IL-1β) in CACC induced rats. Taken together, these findings suggest that Carvacrol may play a beneficial role in DMH/DSS induced experimental rat model and serve as an excellent dietary antioxidant as well as anti-inflammatory agent. It may represent novel therapeutic interventions

  17. Relation of Resemblance in Information Retrieval.

    ERIC Educational Resources Information Center

    Pietilainen, Pirkko

    1982-01-01

    Presents a method for using the amount of semantic information in search-query terms as a weighting factor in constructing a fuzzy relation of resemblance between retrieved items in information retrieval online. Two tables, two figures, and a reference list accompany the text. (Author/JL)

  18. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?

    PubMed Central

    Gehlen, Heidrun

    2016-01-01

    Equine inflammatory airway disease (IAD) and recurrent airway obstruction (RAO) represent a spectrum of chronic inflammatory disease of the airways in horses resembling human asthma in many aspects. Therefore, both are now described as severity grades of equine asthma. Increasing evidence in horses and humans suggests that local pulmonary inflammation is influenced by systemic inflammatory processes and the other way around. Inflammation, coagulation, and fibrinolysis as well as extracellular remodeling show close interactions. Cytology of bronchoalveolar lavage fluid and tracheal wash is commonly used to evaluate the severity of local inflammation in the lung. Other mediators of inflammation, like interleukins involved in the chemotaxis of neutrophils, have been studied. Chronic obstructive pneumopathies lead to remodeling of bronchial walls and lung parenchyma, ultimately causing fibrosis. Matrix metalloproteinases (MMPs) are discussed as the most important proteolytic enzymes during remodeling in human medicine and increasing evidence exists for the horse as well. A systemic involvement has been shown for severe equine asthma by increased acute phase proteins like serum amyloid A and haptoglobin in peripheral blood during exacerbation. Studies focusing on these and further possible inflammatory markers for chronic respiratory disease in the horse are discussed in this review of the literature. PMID:28053371

  19. 2-Chloroadenosine (2-CADO) treatment modulates the pro-inflammatory immune response to prevent acute lung inflammation in BALB/c mice suffering from Klebsiella pneumoniae B5055-induced pneumonia.

    PubMed

    Kumar, Vijay; Harjai, Kusum; Chhibber, Sanjay

    2010-06-01

    Acute lung inflammation (ALI) is a life-threatening pathology and can develop during the course of several clinical conditions such as pneumonia, acid aspiration or sepsis. Adenosine plays a significant role in controlling acute inflammation via binding to A(2A) receptors on inflammatory cells, i.e. neutrophils or macrophages. The present study was designed to evaluate the anti-inflammatory and immunomodulatory effects of 2-chloroadenosine (2-CADO), alone or in combination with amoxicillin/clavulanic acid (AMC), in Klebsiella pneumoniae B5055-induced acute lung infection in mice. Acute lung infection in mice was induced by directly instilling the selected dose (10(4) colony-forming units/mL) of bacteria intranasally. Histopathological examination of the lungs was performed to reveal neutrophil infiltration into the lung alveoli. In addition to the major pro-inflammatory cytokines tumour necrosis factor-alpha (TNFalpha) and interleukin (IL)-1alpha, levels of the anti-inflammatory cytokine IL-10 were also determined. Intranasal instillation of bacteria caused profound neutrophil infiltration into the lung alveoli as well as a significant increase in the levels of pro-inflammatory mediators (i.e. TNFalpha and IL-1alpha). However, intravenous administration of 2-CADO 10 microg/kg/day, alone or in combination with an antibiotic (i.e. AMC), significantly decreased neutrophil infiltration into the lung alveoli. A significant decrease in TNFalpha and IL-1alpha along with elevation of IL-10 levels in the lung homogenate of mice with acute lung infection was observed upon treatment with 2-CADO alone, with no significant decrease in bacterial counts. Moreover, in combination with AMC, 2-CADO exhibited its immunomodulatory action in acute lung infection and prevented ALI, whilst an antibacterial action was exhibited by AMC. 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  20. Non-steroidal Anti-inflammatory Drugs Attenuate Hyperalgesia and Block Upregulation of Trigeminal Ganglionic Sodium Channel 1.7 after Induction of Temporomandibular Joint Inflammation in Rats.

    PubMed

    Bi, Rui Yun; Ding, Yun; Gan, Ye Hua

    2016-03-01

    To investigate the association between the analgesic effect of non-steroidal antiinflammatory drugs (NSAIDs) and sodium channel 1.7 (Nav1.7) expression in the trigeminal ganglion (TG). Temporomandibular joint (TMJ) inflammation was induced by complete Freund's adjuvant (CFA) in female rats. Ibuprofen, diclofenac sodium and meloxicam were given intragastrically before induction of TMJ inflammation. Histopathological evaluation and scoring of TMJ inflammation was used to evaluate the level of inflammation. The head withdrawal threshold and food intake were measured to evaluate TMJ nociceptive responses. The mRNA and protein expression of trigeminal ganglionic Nav1.7 was examined using real-time polymerase chain reaction and western blot. Twenty-four hours after the injection of CFA into the TMJs, NSAIDs attenuated hyperalgesia of inflamed TMJ and simultaneously blocked inflammation-induced upregulation of Nav1.7 mRNA and protein expression in the TG. However, ibuprofen and diclofenac sodium slightly attenuated TMJ inflammation and meloxicam did not affect TMJ inflammation. Attenuation of hyperalgesia of inflamed TMJ by NSAIDs might be associated with their role in blocking upregulation of trigeminal ganglionic Nav1.7.

  1. Inflammatory myopathies.

    PubMed

    Podell, Michael

    2002-01-01

    Inflammatory myopathies are the result of infiltration of inflammatory cells into striated muscle, with or without an association with an underlying cause. Two broad classifications are IIMs and secondary inflammatory myopathies associated with other diseases. Standard diagnostic criteria for inflammatory myopathy include the presence of weakness or loss of specific muscle group function, an increase in CK, EMG changes associated with muscle membrane instability, and histologic evidence of inflammation. Not all these criteria, however, must be present. Fresh-frozen biopsy from two proximal muscles is recommended for biopsy confirmation. IIM can either focally affect head or neck muscles or be more diffuse. MMM is an immune-mediated disease characterized by a humoral antibody produced against the unique type IIM and type I variant mvofibers of masticatory muscles of dogs, which causes inflammation and loss of function of the muscles of mastication. Idiopathic polymyositis can affect focal muscle groups (extraocular, laryngeal) or present as multifocal or diffuse involvement of skeletal muscle in the cat and dog. Familial canine DM is an inflammatory disease of the striated muscle, skin, and vasculature in young Collies, Shetland Sheepdogs (Shelties), and, rarely, Collie-crossbred dogs. Immunosuppressive therapy is the key to successful treatment. Protozoal parasitic myopathies are the most common cause of clinically relevant secondary inflammatory myopathies. The degree of systemic involvement is often the limiting factor to successful treatment. Early recognition of the clinical signs for proper diagnostic testing and institution of appropriate therapy can result in a rewarding outcome in treating inflammatory myopathies in the cat and dog.

  2. Cannabinoids, inflammation, and fibrosis.

    PubMed

    Zurier, Robert B; Burstein, Sumner H

    2016-11-01

    Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs). As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis. A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ(9)-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented. Mention is also made of the noncannabinoid plant components and pyrolysis products, followed by a discussion of 3 synthetic preparations-Cesamet (nabilone; Meda Pharmaceuticals, Somerset, NJ, USA), Marinol (dronabinol; THC; AbbVie, Inc., North Chicago, IL, USA), and Sativex (Cannabis extract; GW Pharmaceuticals, Cambridge United Kingdom)-that have anti-inflammatory effects. A fourth synthetic cannabinoid, ajulemic acid (AJA; CT-3; Resunab; Corbus Pharmaceuticals, Norwood, MA, USA), is discussed in greater detail because it represents the most recent advance in this area and is currently undergoing 3 phase 2 clinical trials by Corbus Pharmaceuticals. The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed. The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances. Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents. Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.-Zurier, R. B., Burstein, S. H. Cannabinoids, inflammation, and fibrosis. © FASEB.

  3. Post-mating inflammatory responses of the uterus.

    PubMed

    Katila, T

    2012-08-01

    This review attempts to summarize the current knowledge on uterine inflammatory response after mating in horses, pigs and cattle. Post-mating endometritis has been extensively studied in horses as it has been considered to cause infertility. The inflammation is known to occur also in cattle, but it has not been investigated to a similar extent. There are a number of publications about mechanisms of post-mating uterine inflammation in pigs, which seem to resemble those in horses. The major focus of this review is the horse, but relevant literature is presented also on swine and cattle. Spermatozoa, seminal plasma and semen extenders play roles in the induction of inflammation. In addition, sperm numbers, concentration and viability, as well as the site of semen deposition may modulate the inflammatory response. Cytokines, polymorphonuclear leucocytes (PMN) and mononuclear cells represent the uterine inflammatory response to mating. Inflammation is the first line of defence against invasion and eliminates excess spermatozoa and bacteria. Semen deposition elicits a massive PMN invasion, followed by phagocytosis of sperm aided by the formation of neutrophil extracellular traps. Exposure of the female genital tract to semen is important also for endometrial receptivity and pre-implantation embryo development. Seminal plasma (SP) and inflammation elicit transient immune tolerance to antigens present in semen. SP contains immune-regulatory molecules that activate and control immune responses to antigens by stimulating expression of cytokines and growth factors and by initiating tissue remodelling. SP also regulates ovarian function. Effective elimination of excess sperm and inflammatory by-products and subsequent rapid return of the endometrium to the normal state is a prerequisite for pregnancy. Uterine backflow, driven by myometrial contractions and requiring a patent cervix, is an important physical tool in uterine drainage.

  4. Pelvic Inflammatory Disease

    MedlinePlus

    Pelvic inflammatory disease (PID) is an infection and inflammation of the uterus, ovaries, and other female reproductive organs. It causes scarring ... United States. Gonorrhea and chlamydia, two sexually transmitted diseases, are the most common causes of PID. Other ...

  5. Pseudohypoparathyroidism presenting with bony deformities resembling rickets.

    PubMed

    Bajpai, Anurag; Sharma, Jyoti; Hari, Pankaj; Bagga, Arvind

    2004-04-01

    Pseudohypoparathyroidism (PHP), characterized by hypocalcemia, hyperphosphatemia and elevated parathormone level, may rarely be associated with bony deformities resembling rickets. The authors report two siblings with clinical and radiological features suggestive of rickets unresponsive to treatment with vitamin D. Low serum calcium, elevated serum phosphate, normal renal functions, raised tubular maximum of phosphate and high serum parathormone were suggestive of PHP. Treatment with 1-hydroxyvitamin D and calcium carbonate led to decrease in bone pain, increase in height and weight and resolution of radiological features. PHP should be suspected in patients with bony deformities, hypocalcemia, elevated blood phosphate levels and normal renal functions.

  6. Anti-inflammatory effects of hydrophilic and lipophilic statins with hyaluronic acid against LPS-induced inflammation in porcine articular chondrocytes.

    PubMed

    Chang, Chih-Hung; Hsu, Yuan-Ming; Chen, Yu-Chun; Lin, Feng-Huei; Sadhasivam, Subramaniam; Loo, Siow-Tung; Savitha, Sivasubramanian

    2014-04-01

    The objective of the study is to understand the therapeutic effects of lipophilic (simvastatin) and hydrophilic statins (pravastatin) combined with/without hyaluronic acid for osteoarthritis by an in vitro LPS-induced inflammatory model of articular chondrocytes. HA in combination with different doses of simvastatin or pravastatin were used. Beside cytotoxicity, the influence of statins on NO production, pro-inflammatory cytokine, inflammatory mediators, and NF-κB p50 protein were analyzed. Finally, TUNEL assay was performed to detect DNA strand breakage. Two statins were less able to lower NF-κB activity when they were administrated along without HA. The gene expression demonstrates that simvastatin and pravastatin had the ability to decrease pro-inflammatory and inflammatory mediator levels. High dose simvastatin with or without HA down regulated inflammatory cytokines, but resulted in higher cytotoxicity. TUNEL assay confirms the regulatory effect of statins with or without HA over the apoptosis of chondrocytes, especially in hydrophilic statins. The significant down-regulation of inflammatory mediators suggests that intra-articular injection of HA in combination with statins might feasibly slow the progress of osteoarthritis. Administration of simvastatin or pravastatin with hyaluronic acid may produce beneficial effects for OA treatment, but with better results when hydrophilic statin was used. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  7. The resolution of inflammation.

    PubMed

    Buckley, Christopher D; Gilroy, Derek W; Serhan, Charles N; Stockinger, Brigitta; Tak, Paul P

    2013-01-01

    In 2012, Nature Reviews Immunology organized a conference that brought together scientists and clinicians from both academia and industry to discuss one of the most pressing questions in medicine--how do we turn off rampant, undesirable inflammation? There is a growing appreciation that, similarly to the initiation of inflammation, the resolution of inflammation is an intricate and active process. Can we therefore harness the mediators involved in resolution responses to treat patients with chronic inflammatory or autoimmune diseases? Here, we ask five of the speakers from the conference to share their thoughts on this emerging field.

  8. Protective effect of a Butea monosperma (Lam.) Taub. flowers extract against skin inflammation: antioxidant, anti-inflammatory and matrix metalloproteinases inhibitory activities.

    PubMed

    Krolikiewicz-Renimel, Isabelle; Michel, Thomas; Destandau, Emilie; Reddy, Madhukar; André, Patrice; Elfakir, Claire; Pichon, Chantal

    2013-07-09

    Butea monosperma (Lam.) Taubert (Syn. Butea frondosa; family Fabaceae) is a common plant of the Indian continent (Das et al., 2011; Sharma and Deshwal, 2011). The brightly orange flowers of this plant are widely used in traditional medicine and more particularly for inflammatory disease. In vitro anti-inflammatory mechanism of a hydroethanolic extract of B. monosperma flowers (BME) and more specifically of an enriched fraction in butrin and isobutrin (BI) was studied using cell culture of Normal Human Keratinocyte, cells involved in the skin inflammatory. Dried and crushed B. monosperma flowers were extracted with Ethanol/H2O (70/30 v/v). The butrin/isobutrin fraction was obtained by centrifugal Partition Chromatography (CPC). Experiments were conducted on UV-B treated normal human epidermis keratinocytes, cells involved in the skin inflammatory response. To evaluate extract anti-inflammatory activity, cytokines IL-1β, IL-6, IL-8, prostaglandin E2 and metalloproteinases MMP-1, -2, -9 and -10 were measured in the cells supernatant. Our data clearly showed that hydroalcoholic B. monosperma flower extract was able to decrease the secretion of IL-1β, IL-6 and IL-8 pro-inflammatory cytokines of -32, -33 and -18% respectively. Interestingly, Prostaglandin E2 production and the secretion of MMP-1, -2, -9 and -10 were also inhibited. Same results were observed in presence of enriched fraction in butrin and isobutrin and confirmed the participation of these molecules in the anti-inflammatory activity. These results explain the anti-inflammatory activity of B. monosperma and confirm the interest to use it in traditional Indian medicine. Moreover, its metalloproteinases inhibitory activities coupled with its anti-inflammatory action also give anti-aging property to this plant. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin

    PubMed Central

    Phua, Terri; Sng, Ming Keat; Tan, Eddie Han Pin; Chee, Dickson Shao Liang; Li, Yinliang; Wee, Jonathan Wei Kiat; Teo, Ziqiang; Chan, Jeremy Soon Kiat; Lim, Maegan Miang Kee; Tan, Chek Kun; Zhu, Pengcheng; Arulampalam, Velmurugesan; Tan, Nguan Soon

    2017-01-01

    Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4−/−) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. A microarray gene expression profile of the colon from DSS-treated ANGPTL4−/− mice was enriched for genes involved in leukocyte migration and infiltration, and showed a close association to inflamed ulcerative colitis (UC), whereas the profile from ANGPTL4+/+ littermates resembled that of non-inflamed UC biopsies. Bone marrow transplantation demonstrates the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation. Using immortalized human colon epithelial cells, we revealed that the ANGPTL4-mediated upregulation of tristetraprolin expression operates through CREB and NF-κB transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation. PMID:28287161

  10. Angiopoietin-like 4 Mediates Colonic Inflammation by Regulating Chemokine Transcript Stability via Tristetraprolin.

    PubMed

    Phua, Terri; Sng, Ming Keat; Tan, Eddie Han Pin; Chee, Dickson Shao Liang; Li, Yinliang; Wee, Jonathan Wei Kiat; Teo, Ziqiang; Chan, Jeremy Soon Kiat; Lim, Maegan Miang Kee; Tan, Chek Kun; Zhu, Pengcheng; Arulampalam, Velmurugesan; Tan, Nguan Soon

    2017-03-13

    Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4(-/-)) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge. A microarray gene expression profile of the colon from DSS-treated ANGPTL4(-/-) mice was enriched for genes involved in leukocyte migration and infiltration, and showed a close association to inflamed ulcerative colitis (UC), whereas the profile from ANGPTL4(+/+) littermates resembled that of non-inflamed UC biopsies. Bone marrow transplantation demonstrates the intrinsic role of colonic ANGPTL4 in regulating leukocyte infiltration during DSS-induced inflammation. Using immortalized human colon epithelial cells, we revealed that the ANGPTL4-mediated upregulation of tristetraprolin expression operates through CREB and NF-κB transcription factors, which in turn, regulates the stability of chemokines. Together, our findings suggest that ANGPTL4 protects against acute colonic inflammation and that its absence exacerbates the severity of inflammation. Our findings emphasize the importance of ANGPTL4 as a novel target for therapy in regulating and attenuating inflammation.

  11. Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics.

    PubMed

    Migale, Roberta; MacIntyre, David A; Cacciatore, Stefano; Lee, Yun S; Hagberg, Henrik; Herbert, Bronwen R; Johnson, Mark R; Peebles, Donald; Waddington, Simon N; Bennett, Phillip R

    2016-06-13

    Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for the development of PTL prevention strategies.

  12. BET protein function is required for inflammation: Brd2 genetic disruption and BET inhibitor JQ1 impair mouse macrophage inflammatory responses.

    PubMed

    Belkina, Anna C; Nikolajczyk, Barbara S; Denis, Gerald V

    2013-04-01

    Histone acetylation regulates activation and repression of multiple inflammatory genes known to play critical roles in chronic inflammatory diseases. However, proteins responsible for translating the histone acetylation code into an orchestrated proinflammatory cytokine response remain poorly characterized. Bromodomain and extraterminal (BET) proteins are "readers" of histone acetylation marks, with demonstrated roles in gene transcription, but the ability of BET proteins to coordinate the response of inflammatory cytokine genes through translation of histone marks is unknown. We hypothesize that members of the BET family of dual bromodomain-containing transcriptional regulators directly control inflammatory genes. We examined the genetic model of brd2 lo mice, a BET protein hypomorph, to show that Brd2 is essential for proinflammatory cytokine production in macrophages. Studies that use small interfering RNA knockdown and a small-molecule inhibitor of BET protein binding, JQ1, independently demonstrate BET proteins are critical for macrophage inflammatory responses. Furthermore, we show that Brd2 and Brd4 physically associate with the promoters of inflammatory cytokine genes in macrophages. This association is absent in the presence of BET inhibition by JQ1. Finally, we demonstrate that JQ1 ablates cytokine production in vitro and blunts the "cytokine storm" in endotoxemic mice by reducing levels of IL-6 and TNF-α while rescuing mice from LPS-induced death. We propose that targeting BET proteins with small-molecule inhibitors will benefit hyperinflammatory conditions associated with high levels of cytokine production.

  13. Potent anti-inflammatory activity of novel microtubule-modulating brominated noscapine analogs.

    PubMed

    Zughaier, Susu; Karna, Prasanthi; Stephens, David; Aneja, Ritu

    2010-02-11

    Noscapine, a plant-derived, non-toxic, over-the-counter antitussive alkaloid has tubulin-binding properties. Based upon the structural resemblance of noscapine to colchicine, a tubulin-binding anti-inflammatory drug, noscapine and its semi-synthetic brominated analogs were examined for in vitro anti-inflammatory activity. Brominated noscapine analogs were found to inhibit cytokine and chemokine release from macrophage cell lines but did not affect cell viability. Brominated noscapine analogs demonstrated anti-inflammatory properties in both TLR- and non-TLR induced in vitro innate immune pathway inflammation models, mimicking septic and sterile infection respectively. In addition, electron microscopy and immunoblotting data indicated that these analogs induced robust autophagy in human macrophages. This study is the first report to identify brominated noscapines as innate immune pathway anti-inflammatory molecules.

  14. Age-dependent effects of peripheral inflammation on the electrophysiological properties of neonatal rat dorsal horn neurons.

    PubMed

    Torsney, Carole; Fitzgerald, Maria

    2002-03-01

    The aim of this study was to investigate the postnatal development of spinal cord neurophysiological mechanisms of inflammatory pain. The effect of hindpaw inflammation on the properties of neonatal spinal dorsal horn cells was investigated in urethane-anesthetized newborn rats using in vivo single-unit extracellular recordings. Responses to cutaneous mechanical and electrical A and C fiber stimulation were recorded at postnatal day (P) 3, 10, and 21 in pups that had received a unilateral intraplantar carageenan injection (1%, 1 microl/g body wt) 2-5 h earlier and compared with age-matched controls. At all three ages, carageenan inflammation increased A fiber evoked sensitization, spontaneous activity, and the suprathreshold response magnitude of dorsal horn cells. Receptive field size, which normally decreases with postnatal age, was unaffected by inflammation in P3 and P10 pups but significantly increased at P21 so that the size distribution closely resembled that in control P3 pups. Mechanical thresholds of individual dorsal horn neurons were not altered by carageenan inflammation at any age. The results show that some dorsal horn cell properties that are likely to underlie inflammatory hypersensitivity such as increased spontaneous activity and response magnitude are observed from the earliest postnatal age examined (P3). However inflammation induced expansion of mechanical receptive field size is not observed until at least the second postnatal week. These results have implications for the postnatal processing of inflammatory pain.

  15. n-3 Polyunsaturated Fatty Acids and Mechanisms to Mitigate Inflammatory Paracrine Signaling in Obesity-Associated Breast Cancer

    PubMed Central

    Monk, Jennifer M.; Turk, Harmony F.; Liddle, Danyelle M.; De Boer, Anna A.; Power, Krista A.; Ma, David W.L.; Robinson, Lindsay E.

    2014-01-01

    Globally, the prevalence of obesity is increasing which subsequently increases the risk of the development of obesity-related chronic diseases. Low-grade chronic inflammation and dysregulated adipose tissue inflammatory mediator/adipokine secretion are well-established in obesity, and these factors increase the risk of developing inflammation-associated cancer. Breast cancer is of particular interest given that increased inflammation within the subcutaneous mammary adipose tissue depot can alter the local tissue inflammatory microenvironment such that it resembles that of obese visceral adipose tissue. Therefore, in obese women with breast cancer, increased inflammatory mediators both locally and systemically can perpetuate inflammation-associated pro-carcinogenic signaling pathways, thereby increasing disease severity. Herein, we discuss some of these inflammation-associated pro-carcinogenic mechanisms of the combined obese breast cancer phenotype and offer evidence that dietary long chain n-3 polyunsaturated fatty acids (PUFA) may have utility in mitigating the severity of obesity-associated inflammation and breast cancer. PMID:25360510

  16. Pulmonary inflammation induced by repeated inhalations of beta(1,3)-D-glucan and endotoxin.

    PubMed Central

    Fogelmark, B.; Sjöstrand, M.; Rylander, R.

    1994-01-01

    In an animal model of hypersensitivity pneumonitis (HP) guinea-pigs were exposed for 5 weeks to an aerosol of bacterial endotoxin, beta(1,3)-D-glucan (curdlan) or a combination. Exposure to endotoxin or curdlan showed only small changes in inflammatory cells in airways or the lung wall, histologically or in terms of enzyme secretion from alveolar macrophages. When the two agents were given together, a histology resembling HP was seen with alveolar infiltrates and early granulomas. Inflammatory cells in airways were increased and enzyme production of macrophages was changed, suggesting an effect of curdlan on the inflammatory regulating capacity of airway macrophages. The results suggest that interference with macrophage function and inflammation are important components in the development of HP. PMID:8199009

  17. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

    PubMed Central

    Gonçalves-de-Albuquerque, Cassiano Felippe; Silva, Adriana Ribeiro; Burth, Patrícia; Castro-Faria, Mauro Velho; Castro-Faria-Neto, Hugo Caire

    2015-01-01

    Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation. PMID:26640323

  18. Tricin, flavonoid from Njavara reduces inflammatory responses in hPBMCs by modulating the p38MAPK and PI3K/Akt pathways and prevents inflammation associated endothelial dysfunction in HUVECs.

    PubMed

    Shalini, V; Pushpan, Chithra K; G, Sindhu; A, Jayalekshmy; A, Helen

    2016-02-01

    Previous studies revealed the potent anti-inflammatory activity of tricin, the active component of Njavara rice bran. Here, we report the involvement of specific signaling pathways in the protective effect of tricin against LPS induced inflammation in hPBMCs and the role of tricin in modulating endothelial dysfunction in LPS induced HUVECs. Pretreatment with tricin (15μM) significantly inhibited the release of TNF-α and was comparable to the specific pathway blockers like ERK inhibitor (PD98059), JNK inhibitor (SP600125) and p38 inhibitor (SB203580), whereas an increased release of TNF-α was observed in PI3K/Akt inhibitor (LY294002) treated cells. Tricin alone and combination treatment of tricin and SB203580 showed more significant inhibition of activation of COX-2 and TNF-α than that of SB203580 alone treated group. Combination treatment of tricin and LY294002 showed increased activation of COX-2 and TNF-α, proved that PI3K activation is essential for the anti-inflammatory effect of tricin. Studies conducted on HUVECs revealed the protective effect of tricin against endothelial dysfunction associated with LPS induced inflammation by inhibiting the activation of proinflammatory mediators like TNF-α, IFN-γ, MCP 1 by modulating NF-κB and MAPK signaling pathways. ELISA and flow cytometric analysis again confirmed the protection of tricin against endothelial damage, especially from the decreased activation of cell adhesion molecules like ICAM-1, VCAM-1 and E-Selectin upon tricin treatment. This work establishes the mechanism behind the potent anti-inflammatory activity of the flavonoid tricin.

  19. Spinal Tuberculosis Resembling Neoplastic Lesions on MRI

    PubMed Central

    Kumar, Anil

    2015-01-01

    Background Tuberculous spondylitis is one of the commonest forms of skeletal tuberculosis in developing countries like India causing significant morbidity due to compression of spinal cord and adjacent nerve roots. Diagnosis and intervention at early stage can prevent permanent damage such as spinal deformity and neurological deficits. Aim The purpose of this study was to demonstrate atypical MRI features in cases of tubercular spondylitis resembling neoplastic lesions and to stress that tuberculous spondylitis should be one of the differential diagnoses in any spinal pathology especially in developing countries. Materials and Methods This was a prospective study done in the patients diagnosed as tuberculous spondylitis on 0.2 T Siemens MRI between June 2011 and December 2014 in a tertiary care hospital in India. Total 529 cases of tubercular spinal lesions were diagnosed. Out of which only 59 patients showed atypical features on MR imaging which resembled neoplastic lesions were included in the study. The diagnosis was confirmed by cytology, histopathology, serology and corroborative findings. Results Lumbo-sacral region involvement (30.5%) is the commonest in our study followed by dorsal and cervical region. Multiple level lesions are seen in 14 cases (23.7%). All the 59 (100%) cases show no involvement of intervetebral disc. Posterior appendage involvement seen in 32 cases (54.2%). Soft tissue component seen in Intraspinal (37.2%) and paraspinal (45.7%) compartments. Cord compression seen in 19 cases (32.2%), out which only 7 cases (11.8%) shows cord oedema. Conclusion On MRI, tubercular spondylitis may have variable pictures on imaging. For any spinal and paraspinal lesions, we should also consider the possibility of tubercular aetiology along with other. Since early diagnosis avoids unnecessary delay in the treatment thereby reducing morbidity and possible complications. PMID:26675162

  20. Prostaglandins and Inflammation

    PubMed Central

    Ricciotti, Emanuela; FitzGerald, Garret A.

    2011-01-01

    Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

  1. [Connective tissue and inflammation].

    PubMed

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  2. Specific inhibition of ICAM-1 effectively reduces bladder inflammation in a rat model of severe non-bacterial cystitis

    PubMed Central

    Zhang, Xiang; He, Hongchao; Lu, Guoliang; Xu, Tianyuan; Qin, Liang; Wang, Xianjin; Jin, Xingwei; Liu, Boke; Zhao, Zhonghua; Shen, Zhoujun; Shao, Yuan

    2016-01-01

    The development and progression of bladder pain syndrome/interstitial cystitis (BPS/IC) is closely related to bladder inflammation. Intercellular adhesion molecule 1 (ICAM-1) is associated with bladder inflammation in BPS/IC. We investigated the effect of specific inhibition of ICAM-1 using an anti-ICAM-1 antibody (AIA) on bladder inflammation in a rat model of severe non-bacterial cystitis (NBC) resembling BPS/IC by evaluating the bladder inflammation grade, mast cell infiltration and related cytokines and receptors. We also compared the effects of AIA with the COX-2 inhibitor celecoxib and the neurokinin-1 receptor (NK1R) inhibitor aprepitant. Our NBC model was established by intraperitoneal injection of cyclophosphamide combined with intravesical protamine/lipopolysaccharide, which resulted in severe bladder inflammation and increased mast cell infiltration, similar to the pathological changes of BPS/IC. Inhibition of ICAM-1 by AIA significantly decreased the bladder inflammation grade and mast cell counts, which was accompanied by a reduction of purinergic receptors (P2X2/P2X3), prostaglandin E2, EP1/EP2 receptors, TNF-α, NK1R, and ICAM-1. Moreover, AIA showed superior effects to those of celecoxib and aprepitant treatment in improving the bladder inflammatory response. Our results suggest that ICAM-1 may play a critical role in bladder inflammation in severe NBC and may be used as a novel therapeutic target in non-bacterial bladder inflammation such as BPS/IC. PMID:27782122

  3. Evaluation of the Anti-Inflammatory, Antioxidant and Immunomodulatory Effects of the Organic Extract of the Red Sea Marine Sponge Xestospongia testudinaria against Carrageenan Induced Rat Paw Inflammation.

    PubMed

    El-Shitany, Nagla A; Shaala, Lamiaa A; Abbas, Aymn T; Abdel-Dayem, Umama A; Azhar, Esam I; Ali, Soad S; van Soest, Rob W M; Youssef, Diaa T A

    2015-01-01

    Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4-6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 β(IL-1β) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea sponge

  4. Evaluation of the Anti-Inflammatory, Antioxidant and Immunomodulatory Effects of the Organic Extract of the Red Sea Marine Sponge Xestospongia testudinaria against Carrageenan Induced Rat Paw Inflammation

    PubMed Central

    El-Shitany, Nagla A.; Abbas, Aymn T.; Abdel-dayem, Umama A.; Azhar, Esam I.; Ali, Soad S.; van Soest, Rob W. M.

    2015-01-01

    Marine sponges are found to be a rich source of bioactive compounds which show a wide range of biological activities including antiviral, antibacterial, and anti-inflammatory activities. This study aimed to investigate the possible anti-inflammatory, antioxidant and immunomodulator effects of the methanolic extract of the Red Sea marine sponge Xestospongia testudinaria. The chemical composition of the Xestospongia testudinaria methanolic extract was determined using Gas chromatography-mass spectroscopy (GC-MS) analysis. DPPH (2, 2-diphenyl-1-picryl-hydrazyl) was measured to assess the antioxidant activity of the sponge extract. Carrageenan-induced rat hind paw edema was adopted in this study. Six groups of rats were used: group1: Control, group 2: Carrageenan, group 3: indomethacin (10 mg/kg), group 4–6: Xestospongia testudinaria methanolic extract (25, 50, and 100 mg/kg). Evaluation of the anti-inflammatory activity was performed by both calculating the percentage increase in paw weight and hisopathologically. Assessment of the antioxidant and immunomodulatory activity was performed. GC-MS analysis revealed that there were 41 different compounds present in the methanolic extract. Sponge extract exhibited antioxidant activity against DPPH free radicals. Xestospongia testudinaria methanolic extract (100 mg/kg) significantly decreased % increase in paw weight measured at 1, 2, 3 and 4 h after carrageenan injection. Histopathologically, the extract caused a marked decrease in the capillary congestion and inflammatory cells infiltrate. The extract decreased paw malondialdehyde (MDA) and nitric oxide (NO) and increased the reduced glutathione (GSH), glutathione peroxidase (GPx), and catalase (CAT) activity. It also decreased the inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1 β(IL-1β) and IL-6. The results of this study demonstrated the anti-inflammatory, antioxidant, and immunomodulatory effects of the methanolic extract of the Red Sea

  5. Necrotizing meningoencephalitis of Pug dogs associates with dog leukocyte antigen class II and resembles acute variant forms of multiple sclerosis.

    PubMed

    Greer, K A; Wong, A K; Liu, H; Famula, T R; Pedersen, N C; Ruhe, A; Wallace, M; Neff, M W

    2010-08-01

    Necrotizing meningoencephalitis (NME) is a disorder of Pug Dogs that appears to have an immune etiology and high heritability based on population studies. The present study was undertaken to identify a genetic basis for the disease. A genome-wide association scan with single tandem repeat (STR) markers showed a single strong association near the dog leukocyte antigen (DLA) complex on CFA12. Fine resolution mapping with 27 STR markers on CFA12 further narrowed association to the region containing DLA-DRB1, -DQA1 and, -DQB1 genes. Sequencing confirmed that affected dogs were more likely to be homozygous for specific alleles at each locus and that these alleles were linked, forming a single high risk haplotype. The strong DLA class II association of NME in Pug Dogs resembles that of human multiple sclerosis (MS). Like MS, NME appears to have an autoimmune basis, involves genetic and nongenetic factors, has a relatively low incidence, is more frequent in females than males, and is associated with a vascularly orientated nonsuppurative inflammation. However, NME of Pug Dogs is more aggressive in disease course than classical human MS, appears to be relatively earlier in onset, and involves necrosis rather than demyelination as the central pathobiologic feature. Thus, Pug Dog encephalitis (PDE) shares clinical features with the less common acute variant forms of MS. Accordingly, NME of Pug Dogs may represent a naturally occurring canine model of certain idiopathic inflammatory disorders of the human central nervous system.

  6. Nucleotide signalling during inflammation

    PubMed Central

    Idzko, Marco; Ferrari, Davide; Eltzschig, Holger K.

    2014-01-01

    Inflammatory conditions are associated with the extracellular release of nucleotides, particularly ATP. In the extracellular compartment, ATP predominantly functions as a signalling molecule through the activation of purinergic P2 receptors. Metabotropic P2Y receptors are G-protein-coupled, whereas ionotropic P2X receptors are ATP-gated ion channels. Here we discuss how signalling events through P2 receptors alter the outcomes of inflammatory or infectious diseases. Recent studies implicate a role for P2X/P2Ysignalling in mounting appropriate inflammatory responses critical for host defence against invading pathogens or tumours. Conversely, P2X/P2Y signalling can promote chronic inflammation during ischaemia and reperfusion injury, inflammatory bowel disease or acute and chronic diseases of the lungs. Although nucleotide signalling has been used clinically in patients before, research indicates an expanding field of opportunities for specifically targeting individual P2 receptors for the treatment of inflammatory or infectious diseases. PMID:24828189

  7. Inflammatory Bowel Diseases: When Natural Friends Turn into Enemies—The Importance of CpG Motifs of Bacterial DNA in Intestinal Homeostasis and Chronic Intestinal Inflammation

    PubMed Central

    Obermeier, Florian; Hofmann, Claudia; Falk, Werner

    2010-01-01

    From numerous studies during the last years it became evident that bacteria and bacterial constituents play a decisive role both in the maintenance of intestinal immune homeostasis as well as in the development and perpetuation of chronic intestinal inflammation. In this review we focus on the role of bacterial DNA which is a potent immunomodulatory component of the bacterial flora. Bacterial DNA has been shown to be protective against experimental colitis. In contrast bacterial DNA essentially contributes to the perpetuation of an already established chronic intestinal inflammation in a Toll-like receptor (TLR)9-dependent manner. This dichotomic action may be explained by a different activation status of essential regulators of TLR signaling like Glycogen synthase kinase 3-β (GSK3-β) depending on the pre-activation status of the intestinal immune system. In this review we suggest that regulators of TLR signaling may be interesting therapeutic targets in IBD aiming at the restoration of intestinal immune homeostasis. PMID:21188217

  8. Proteomic Analysis of Anti-inflammatory Effects of a Kampo (Japanese Herbal) Medicine "Shoseiryuto (Xiao-Qing-Long-Tang)" on Airway Inflammation in a Mouse Model.

    PubMed

    Nagai, Takayuki; Nakao, Marino; Shimizu, Yuliko; Kodera, Yoshio; Oh-Ishi, Masamichi; Maeda, Tadakazu; Yamada, Haruki

    2011-01-01

    Effects of a Kampo (Japanese herbal) medicine "shoseiryuto (SST, xiao-qing-long-tang in Chinese)", which has been used for the treatment of allergic bronchial asthma clinically, were examined on ovalbumin (OVA)-sensitized allergic airway inflammation model (i.e., bronchial asthma) in a mouse. When SST was orally administered at 0.5 g kg(-1) day(-1) from day 1 to 6 after OVA inhalation, SST reduced the inflammation in lung tissue, the number of eosinophils and the OVA-specific immunoglobulin E (IgE) antibody titer in bronchoalveolar lavage (BAL) fluids at 7 days after the OVA inhalation. SST also reduced the airway hyperreactivity at 6 days after the OVA inhalation. Proteomic analysis with the agarose two-dimensional electrophoresis showed that the expression of spectrin α2 was reduced in the lung tissue of OVA-sensitized mice and SST recovered the expression. Western blot and immunohistochemical analyses of lung tissue also confirmed this result. When prednisolone was orally administered at 3 mg kg(-1) day(-1) from day 1 to 6 after OVA inhalation, the inflammation in lung tissue, the number of eosinophils in BAL fluids and airway hyperreactivity were reduced in the OVA-sensitized mice. However, prednisolone did not reduce the OVA-specific IgE antibody titer in BAL fluids and did not recover the expression of spectrin α2 in lung tissue. These results suggest that at least a part of action mechanism of SST against OVA-sensitized allergic airway inflammation in a mouse model is different from that of prednisolone.

  9. Distinct commensals induce interleukin-1β via NLRP3 inflammasome in inflammatory monocytes to promote intestinal inflammation in response to injury

    PubMed Central

    Seo, Sang-Uk; Kamada, Nobuhiko; Muñoz-Planillo, Raúl; Kim, Yun-Gi; Kim, Donghyun; Koizumi, Yukiko; Hasegawa, Mizuho; Himpsl, Stephanie D.; Browne, Hilary P.; Lawley, Trevor D.; Mobley, Harry L. T.; Inohara, Naohiro; Núñez, Gabriel

    2015-01-01

    SUMMARY The microbiota stimulate inflammation, but the signaling pathways and the members of the microbiota involved remain poorly understood. We found that the microbiota induce interleukin-1β (IL-1β) release upon intestinal injury and this is mediated via the NLRP3 inflammasome. Enterobacteriaceae and in particular the pathobiont Proteus mirabilis, induced robust IL-1β release that was comparable to that induced by the pathogen Salmonella. Upon epithelial injury, production of IL-1β in the intestine was largely mediated by intestinal Ly6Chigh monocytes, required chemokine receptor CCR2 and was abolished by deletion of IL-1β in CCR2+ blood monocytes. Furthermore, colonization with P. mirabilis promoted intestinal inflammation upon intestinal injury via the production of hemolysin which required NLRP3 and IL-1 receptor signaling in vivo. Thus, upon intestinal injury, selective members of the microbiota stimulate newly recruited monocytes to induce NLRP3-dependent IL-1β release which promotes inflammation in the intestine. PMID:25862092

  10. Effect of the Toll-like receptor 4 antagonist eritoran on retinochoroidal inflammatory damage in a rat model of endotoxin-induced inflammation.

    PubMed

    Ekici, Feyzahan; Karaca, Emine Esra; Korkmaz, Safak; Yüksel, Osman; Gülbahar, Özlem; Alper, Murat; Ercan, Sevim; Or, Meral

    2014-01-01

    We investigated the effect of eritoran, a Toll-like receptor 4 antagonist, on retinochoroidal inflammatory damage in an endotoxin-induced inflammatory rat model. Endotoxin-induced inflammatory model was obtained by intraperitoneal injection of 1.5 mg/kg lipopolysaccharide (LPS). Group 1 had control rats; in groups 2-3 LPS and 0.5 mg/kg sterile saline were injected; and in groups 4-5 LPS and 0.5 mg/kg eritoran were injected. Blood samples were taken and eyes were enucleated after 12 hours (h) (groups 2 and 4) or 24 hours (Groups 3 and 5). Tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels in the serum and retinochoroidal tissue and nuclear factor kappa-B (NFκB) levels in retinochoroidal tissue were determined. Histopathological examination was performed and retinochoroidal changes were scored. Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. Serum TNF-α and retinochoroidal tissue NFκB levels were similar to control animals at the 24th h of the study. Eritoran significantly reversed histopathological damage after 24 h. Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters.

  11. Effect of the Toll-Like Receptor 4 Antagonist Eritoran on Retinochoroidal Inflammatory Damage in a Rat Model of Endotoxin-Induced Inflammation

    PubMed Central

    Karaca, Emine Esra; Korkmaz, Şafak; Yüksel, Osman; Gülbahar, Özlem; Alper, Murat; Ercan, Sevim; Or, Meral

    2014-01-01

    Purpose. We investigated the effect of eritoran, a Toll-like receptor 4 antagonist, on retinochoroidal inflammatory damage in an endotoxin-induced inflammatory rat model. Methods. Endotoxin-induced inflammatory model was obtained by intraperitoneal injection of 1.5 mg/kg lipopolysaccharide (LPS). Group 1 had control rats; in groups 2-3 LPS and 0.5 mg/kg sterile saline were injected; and in groups 4-5 LPS and 0.5 mg/kg eritoran were injected. Blood samples were taken and eyes were enucleated after 12 hours (h) (groups 2 and 4) or 24 hours (Groups 3 and 5). Tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) levels in the serum and retinochoroidal tissue and nuclear factor kappa-B (NFκB) levels in retinochoroidal tissue were determined. Histopathological examination was performed and retinochoroidal changes were scored. Results. Eritoran treatment resulted in lower levels of TNF-α, MDA, and NFκB after 12 h which became significant after 24 h. Serum TNF-α and retinochoroidal tissue NFκB levels were similar to control animals at the 24th h of the study. Eritoran significantly reversed histopathological damage after 24 h. Conclusions. Eritoran treatment resulted in less inflammatory damage in terms of serum and retinochoroidal tissue parameters. PMID:25165412

  12. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis

    PubMed Central

    2012-01-01

    Background Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. Methods We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Results Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis. Conclusions Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway. PMID:22920325

  13. The effect of sulindac, a non-steroidal anti-inflammatory drug, attenuates inflammation and fibrosis in a mouse model of chronic pancreatitis.

    PubMed

    Bai, Han; Chen, Xiaokai; Zhang, Lin; Dou, Xiaoguang

    2012-08-24

    Chronic pancreatitis is characterized by progressive fibrosis, pain and loss of exocrine and endocrine functions. The long-standing chronic pancreatitis and its associated pancreatic fibrosis are the most common pathogenic events involved in human pancreatic carcinogenesis, but the therapeutic strategies to chronic pancreatitis and the chemoprevention of pancreatic carcinogenesis are very limited. We investigated the effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on inhibition of chronic pancreatitis in a caerulein induced chronic pancreatitis mouse model. Sulindac significantly reduced the severity of chronic pancreatitis including the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The protein expression of phosphorylation of MEK/ERK was inhibited in the chronic pancreatic tissues by sulindac treatment as measured by Western blot assay. The levels of inflammatory cytokines including TNF-α and MCP-1 were also significantly decreased with sulindac treatment, as well as the expression of TGF-β, PDGF-β, SHH and Gli in the chronic pancreatic tissue detected by qPCR assay and confirmed by western blot assay. The activation of pancreatic satellet cells was also inhibited by sulindac as measured by the activity of α-smooth muscle actin (α-SMA) in the pancreatic tissue of chronic pancreatitis. Sulindac is a promising reagent for the treatment of chronic pancreatitis via inhibition of inflammatory cell infiltration and stromal fibrosis, the inhibitory effect of sulindac on chronic pancreatitis may through targeting the activation ERK/MAPK signaling pathway.

  14. Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory.

    PubMed

    Wanner, Samuel P; Garami, Andras; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Coimbra, Cândido C; Romanovsky, Andrej A

    2012-01-15

    Studies in young rodents have shown that the transient receptor potential vanilloid-1 (TRPV1) channel plays a suppressive role in the systemic inflammatory response syndrome (SIRS) by inhibiting production of tumor necrosis factor (TNF)α and possibly by other mechanisms. We asked whether the anti-inflammatory role of TRPV1 changes with age. First, we studied the effect of AMG517, a selective and potent TRPV1 antagonist, on aseptic, lipopolysaccharide (LPS)-induced SIRS in young (12 wk) mice. In agreement with previous studies, AMG517 increased LPS-induced mortality in the young. We then studied the effects of TRPV1 antagonism (AMG517 or genetic deletion of TRPV1) on SIRS in middle-aged (43-44 wk) mice. Both types of TRPV1 antagonism delayed and decreased LPS-induced mortality, indicating a reversal of the anti-inflammatory role of TRPV1 with aging. In addition, deletion of TRPV1 decreased the serum TNFα response to LPS, suggesting that the suppressive control of TRPV1 on TNFα production is also reversed with aging. In contrast to aseptic SIRS, polymicrobial sepsis (induced by cecal ligation and puncture) caused accelerated mortality in aged TRPV1-deficient mice as compared with wild-type littermates. The recovery of TRPV1-deficient mice from hypothermia associated with the cecal ligation and puncture procedure was delayed. Hence, the reversal of the anti-inflammatory role of TRPV1 found in the aged and their decreased systemic inflammatory response are coupled with suppressed defense against microbial infection. These results caution that TRPV1 antagonists, widely viewed as new-generation painkillers, may decrease the resistance of older patients to infection and sepsis.

  15. Body elimination attitude family resemblance in Kuwait.

    PubMed

    Al-Fayez, Ghenaim; Awadalla, Abdelwahid; Arikawa, Hiroko; Templer, Donald I; Hutton, Shane

    2009-12-01

    The purpose of the present study was to determine the family resemblance of attitude toward body elimination in Kuwaiti participants. This study was conceptualized in the context of the theories of moral development, importance of cleanliness in the Muslim religion, cross-cultural differences in personal hygiene practices, previous research reporting an association between family attitudes and body elimination attitude, and health implications. The 24-item Likert-type format Body Elimination Attitude Scale-Revised was administered to 277 Kuwaiti high school students and 437 of their parents. Females scored higher, indicating greater disgust, than the males. Moreover, sons' body elimination attitude correlated more strongly with fathers' attitude (r = .85) than with that of the mothers (r = .64). Daughters' attitude was similarly associated with the fathers' (r = .89) and the mothers' attitude (r = .86). The high correlations were discussed within the context of Kuwait having a collectivistic culture with authoritarian parenting style. The higher adolescent correlations, and in particular the boys' correlation with fathers than with mothers, was explained in terms of the more dominant role of the Muslim father in the family. Public health and future research implications were suggested. A theoretical formulation was advanced in which "ideal" body elimination attitude is relative rather than absolute, and is a function of one's life circumstances, one's occupation, one's culture and subculture, and the society that one lives in.

  16. Giant sublingual epidermoid cyst resembling plunging ranula

    PubMed Central

    Verma, Sandeep; Kushwaha, Jitendra Kumar; Sonkar, A A; Kumar, Rahul; Gupta, Rajni

    2012-01-01

    Epidermoid and dermoid cysts represent less than 0.01% of all oral cavity cysts. We describe a rare case of large epidermoid cyst in floor of mouth, with an oral as well as submental component resembling plunging ranula reported in the literature from India. We present a case of a 16-year-old girl with complaints of a mass in sublingual region, difficulty chewing, and dysphagia for about 5 months. Fine-needle aspiration cytology showed keratin flakes and proteinaceous material. Contrast-enhanced CT oral cavity was done and showed 7.0 × 5 × 4.5 cm well-circumscribed non-enhancing cystic mass extending into the floor of the mouth. On examination, a firm swelling was noticed in the submental area, extending down to the thyroid notch. The patient underwent surgical removal of the mass. On histopathology, acidophilic stratum corneum and basophilic dot like staining of stratum granulosum, which is the hallmark of an epidermoid cyst, were seen. PMID:23833501

  17. Evolving functions of endothelial cells in inflammation.

    PubMed

    Pober, Jordan S; Sessa, William C

    2007-10-01

    Inflammation is usually analysed from the perspective of tissue-infiltrating leukocytes. Microvascular endothelial cells at a site of inflammation are both active participants in and regulators of inflammatory processes. The properties of endothelial cells change during the transition from acute to chronic inflammation and during the transition from innate to adaptive immunity. Mediators that act on endothelial cells also act on leukocytes and vice versa. Consequently, many anti-inflammatory therapies influence the behaviour of endothelial cells and vascular therapeutics influence inflammation. This Review describes the functions performed by endothelial cells at each stage of the inflammatory process, emphasizing the principal mediators and signalling pathways involved and the therapeutic implications.

  18. Inflammatory biomarkers for AMD.

    PubMed

    Stanton, Chloe M; Wright, Alan F

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years.Environmental and genetic risk-factors implicate chronic inflammation in the etiology of AMD, contributing to the formation of drusen, retinal pigment epithelial cell dysfunction and photoreceptor cell death. Consistent with a role for chronic inflammation in AMD pathogenesis, several inflammatory mediators, including complement components, chemokines and cytokines, are elevated at both the local and systemic levels in AMD patients. These mediators have diverse roles in the alternative complement pathway, including recruitment of inflammatory cells, activation of the inflammasome, promotion of neovascularisation and in the resolution of inflammation. The utility of inflammatory biomarkers in assessing individual risk and progression of the disease is controversial. However, understanding the role of these inflammatory mediators in AMD onset, progression and response to treatment may increase our knowledge of disease pathogenesis and provide novel therapeutic options in the future.

  19. Systems biology and inflammation.

    PubMed

    Vodovotz, Yoram; An, Gary

    2010-01-01

    Inflammation is a complex, multiscale biological response to threats - both internal and external - to the body, which is also required for proper healing of injured tissue. In turn, damaged or dysfunctional tissue stimulates further inflammation. Despite continued advances in characterizing the cellular and molecular processes involved in the interactions between inflammation and tissue damage, there exists a significant gap between the knowledge of mechanistic pathophysiology and the development of effective therapies for various inflammatory conditions. We have suggested the concept of translational systems biology, defined as a focused application of computational modeling and engineering principles to pathophysiology primarily in order to revise clinical practice. This chapter reviews the existing, translational applications of computational simulations and related approaches as applied to inflammation.

  20. Primary laryngeal cryptococcosis resembling laryngeal carcinoma.

    PubMed

    Tamagawa, Shunji; Hotomi, Muneki; Yuasa, Jun; Tuchihashi, Shigeki; Yamauchi, Kazuma; Togawa, Akihisa; Yamanaka, Noboru

    2015-08-01

    A case of an 82-year-old female with primary laryngeal cryptococcosis who had undergone long-term corticosteroid therapy for chronic obstructive pulmonary disease and rheumatoid arthritis is reported. She complained hoarseness with swallowing pain and irritability of the larynx for over a month. Endoscopic examination revealed a white, exudative irregular region on right arytenoid that mimicked a laryngeal carcinoma. Histological examination showed pseudoepitheliomatous hyperplasia and severe submucosal inflammation with ovoid budding yeasts by Grocott's stain. A serological study indicated a high titer of cryptococcal antigen. After treating with oral fluconazole for 3 months, her primary lesion of larynx turned to be clear. We implicate a long-term use of steroids as the significant risk factor in developing cryptococcosis of the larynx. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Anti-inflammatory Diets.

    PubMed

    Sears, Barry

    2015-01-01

    Chronic disease is driven by inflammation. This article will provide an overview on how the balance of macronutrients and omega-6 and omega-3 fatty acids in the diet can alter the expression of inflammatory genes. In particular, how the balance of the protein to glycemic load of a meal can alter the generation of insulin and glucagon and the how the balance of omega-6 and omega-3 fatty acids can effect eicosanoid formation. Clinical results on the reduction of inflammation following anti-inflammatory diets are discussed as well as the molecular targets of anti-inflammatory nutrition. To overcome silent inflammation requires an anti-inflammatory diet (with omega-3s and polyphenols, in particular those of Maqui). The most important aspect of such an anti-inflammatory diet is the stabilization of insulin and reduced intake of omega-6 fatty acids. The ultimate treatment lies in reestablishing hormonal and genetic balance to generate satiety instead of constant hunger. Anti-inflammatory nutrition, balanced 40:30:30 with caloric restriction, should be considered as a form of gene silencing technology, in particular the silencing of the genes involved in the generation of silent inflammation. To this anti-inflammatory diet foundation supplemental omega-3 fatty acids at the level of 2-3 g of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day should be added. Finally, a diet rich in colorful, nonstarchy vegetables would contribute adequate amounts of polyphenols to help not only to inhibit nuclear factor (NF)-κB (primary molecular target of inflammation) but also activate AMP kinase. Understanding the impact of an anti-inflammatory diet on silent inflammation can elevate the diet from simply a source of calories to being on the cutting edge of gene-silencing technology.

  2. Unsaturated lipid bodies as a hallmark of inflammation studied by Raman 2D and 3D microscopy

    NASA Astrophysics Data System (ADS)

    Czamara, K.; Majzner, K.; Selmi, A.; Baranska, M.; Ozaki, Y.; Kaczor, A.

    2017-01-01

    Endothelial HMEC-1 cells incubated with pro-inflammatory cytokine TNF-α for 6 and 24 hours were studied as a model of inflammation using Raman imaging. Striking changes in distribution, composition and concentration of cellular lipids were observed after exposure to TNF-α compared to the control. In particular, 3D Raman imaging revealed a significant increase in the amount of lipid entities formed under inflammation. Lipid bodies were randomly distributed in the cytoplasm and two types of droplets were assembled: more saturated one, in spectral characteristics resembling phosphatidylcholine and saturated cholesteryl esters, observed also in the control, and highly unsaturated one, containing also cholesterols, being a hallmark of inflamed cells. The statistical analysis showed that the number of lipid bodies was significantly dependent on the exposure time to TNF-α. Overall, observed formation of unsaturated lipid droplets can be directly correlated with the increase in production of prostacyclins - endogenous inflammation mediators.

  3. Unsaturated lipid bodies as a hallmark of inflammation studied by Raman 2D and 3D microscopy

    PubMed Central

    Czamara, K.; Majzner, K.; Selmi, A.; Baranska, M.; Ozaki, Y.; Kaczor, A.

    2017-01-01

    Endothelial HMEC-1 cells incubated with pro-inflammatory cytokine TNF-α for 6 and 24 hours were studied as a model of inflammation using Raman imaging. Striking changes in distribution, composition and concentration of cellular lipids were observed after exposure to TNF-α compared to the control. In particular, 3D Raman imaging revealed a significant increase in the amount of lipid entities formed under inflammation. Lipid bodies were randomly distributed in the cytoplasm and two types of droplets were assembled: more saturated one, in spectral characteristics resembling phosphatidylcholine and saturated cholesteryl esters, observed also in the control, and highly unsaturated one, containing also cholesterols, being a hallmark of inflamed cells. The statistical analysis showed that the number of lipid bodies was significantly dependent on the exposure time to TNF-α. Overall, observed formation of unsaturated lipid droplets can be directly correlated with the increase in production of prostacyclins - endogenous inflammation mediators. PMID:28098251

  4. Evaluation of the anti-inflammatory effects of two platelet-rich gel supernatants in an in vitro system of cartilage inflammation.

    PubMed

    Ríos, D L; López, C; Carmona, J U

    2015-12-01

    To study, in normal cartilage explants (CEs) challenged with lipopolysaccharide (LPS), the temporal effects (at 48 and 96h) of leukocyte- and platelet-rich gel (L-PRG) and pure platelet-rich gel (P-PRG) supernatants on the production and degradation of platelet-associated growth factors (GFs) (platelet-derived GF isoform BB [PDGF-BB] and transforming growth factor beta-1 [TGF-β1]), pro-inflammatory (tumour necrosis factor alpha [TNF-α]) and anti-inflammatory cytokines (interleukin 4 [IL-4] and IL-1 receptor antagonist [IL-1ra]). CEs from six horses were challenged with LPS and cultured for 96h with L-PRG and P-PRG supernatants at concentrations of 25% and 50%, respectively. The CE culture medium was changed every 48h and used for determination, by ELISA, of PDGF-BB, TGF-β1, TNF-α, IL-4 and IL-1ra. Both the 25% and 50% PRG supernatants produced a different molecular profile in the culture media, unlike that of the CE challenged with LPS only. 50% L-PRG produced the most sustained release of growth factors and anti-inflammatory cytokines, although it produced the highest TNF-α release. PDGF-BB was significantly correlated with IL-1ra and TNF-α concentrations, whereas TNF-α was correlated with IL-4. 50% L-PRG supernatant produced a more sustained concentration of growth factors and anti-inflammatory cytokines than the other hemoderivatives evaluated. This substance could be evaluated in animal models of arthritis or in patients with arthropathies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. The Macrophage Inflammatory Proteins MIP1α (CCL3) and MIP2α (CXCL2) in Implant-Associated Osteomyelitis: Linking Inflammation to Bone Degradation

    PubMed Central

    Dapunt, Ulrike; Maurer, Susanne; Giese, Thomas; Gaida, Matthias Martin; Hänsch, Gertrud Maria

    2014-01-01

    Bacterial infections of bones remain a serious complication of endoprosthetic surgery. These infections are difficult to treat, because many bacterial species form biofilms on implants, which are relatively resistant towards antibiotics. Bacterial biofilms elicit a progressive local inflammatory response, resulting in tissue damage and bone degradation. In the majority of patients, replacement of the prosthesis is required. To address the question of how the local inflammatory response is linked to bone degradation, tissue samples were taken during surgery and gene expression of the macrophage inflammatory proteins MIP1α (CCL3) and MIP2α (CXCL2) was assessed by quantitative RT-PCR. MIPs were expressed predominantly at osteolytic sites, in close correlation with CD14 which was used as marker for monocytes/macrophages. Colocalisation of MIPs with monocytic cells could be confirmed by histology. In vitro experiments revealed that, aside from monocytic cells, also osteoblasts were capable of MIP production when stimulated with bacteria; moreover, CCL3 induced the differentiation of monocytes to osteoclasts. In conclusion, the multifunctional chemokines CCL3 and CXCL2 are produced locally in response to bacterial infection of bones. In addition to their well described chemokine activity, these cytokines can induce generation of bone resorbing osteoclasts, thus providing a link between bacterial infection and osteolysis. PMID:24795505

  6. [Crohn's disease with the onset resembling systemic lupus erythematosus].

    PubMed

    Shimizu, T; Nishinarita, S; Son, K; Tomita, Y; Yoshihiro; Matsukawa; Kitamura, N; Horie, T; Baba, M; Hiranuma, M

    1999-06-01

    We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

  7. Oral green tea catechin metabolites are incorporated into human skin and protect against UV radiation-induced cutaneous inflammation in association with reduced production of pro-inflammatory eicosanoid 12-hydroxyeicosatetraenoic acid.

    PubMed

    Rhodes, Lesley E; Darby, Gemma; Massey, Karen A; Clarke, Kayleigh A; Dew, Tristan P; Farrar, Mark D; Bennett, Susan; Watson, Rachel E B; Williamson, Gary; Nicolaou, Anna

    2013-09-14

    Green tea catechins (GTC) reduce UV radiation (UVR)-induced inflammation in experimental models, but human studies are scarce and their cutaneous bioavailability and mechanism of photoprotection are unknown. We aimed to examine oral GTC cutaneous uptake, ability to protect human skin against erythema induced by a UVR dose range and impact on potent cyclo-oxygenase- and lipoxygenase-produced mediators of UVR inflammation, PGE2 and 12-hydroxyeicosatetraenoic acid (12-HETE), respectively. In an open oral intervention study, sixteen healthy human subjects (phototype I/II) were given low-dose GTC (540 mg) with vitamin C (50 mg) daily for 12 weeks. Pre- and post-supplementation, the buttock skin was exposed to UVR and the resultant erythema quantified. Skin blister fluid and biopsies were taken from the unexposed and the UVR-exposed skin 24 h after a pro-inflammatory UVR challenge (three minimal erythema doses). Urine, skin tissue and fluid were analysed for catechin content and skin fluid for PGE2 and 12-HETE by liquid chromatography coupled to tandem MS. A total of fourteen completing subjects were supplement compliant (twelve female, median 42.5 years, range 29-59 years). Benzoic acid levels were increased in skin fluid post-supplementation (P= 0.03), and methylated gallic acid and several intact catechins and hydroxyphenyl-valerolactones were detected in the skin tissue and fluid. AUC analysis for UVR erythema revealed reduced response post-GTC (P= 0.037). Pre-supplementation, PGE2 and 12-HETE were UVR induced (P= 0.003, 0.0001). After GTC, UVR-induced 12-HETE reduced from mean 64 (sd 42) to 41 (sd 32) pg/μl (P= 0.01), while PGE2 was unaltered. Thus, GTC intake results in the incorporation of catechin metabolites into human skin associated with abrogated UVR-induced 12-HETE; this may contribute to protection against sunburn inflammation and potentially longer-term UVR-mediated damage.

  8. Where Does Inflammation Fit?

    PubMed

    Biasucci, Luigi M; La Rosa, Giulio; Pedicino, Daniela; D'Aiello, Alessia; Galli, Mattia; Liuzzo, Giovanna

    2017-09-01

    This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure. In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship. In particular, recent evidence underlies peculiar aspects of the phenomenon: oxidative stress and autophagy; DAMPS and TLR-4 signaling activation; different macrophages lineage and the contribution of NLRP-3 inflammasome; adaptive immune system. A possible explanation that could unify the pathogenic mechanism of these different conditions is the rising evidence that increased bowel permeability may allow translation of gut microbioma product into the circulation. These findings clearly establish the role of inflammation as the great trigger for two of the major cardiovascular causes of death and morbidity. Further studies are needed, to better clarify the issue and to define more targeted approaches to reduce pathological inflammation while preserving the physiological one.

  9. GASTRIN, INFLAMMATION, AND CARCINOGENESIS

    PubMed Central

    Chao, Celia; Hellmich, Mark R.

    2014-01-01

    Purpose of review Chronic infection of the gastric mucosa with Helicobacter pylori has long been recognized as a significant risk factor for gastric cancer, and indeed, this model represents the prototypical inflammation-associated cancer. In this review, we present the latest clinical and experimental evidence showing that gastrin peptides and their receptors (the cholecystokinin [CCK2] receptors) potentiate the progression of gastric cancer and other gastrointestinal malignancies in the presence of inflammation. Recent Findings We highlight the feed-forward mechanisms by which gastrin and CCK2 receptor expression are upregulated during inflammation and in GI cancers, summarize gastrin’s pro-inflammatory role by inducing the production cyclooxgenase-2 (COX-2) and interleukin-8 (IL-8), and relate evidence suggesting that gastrin and their receptors modulate the function of immune cells and fibroblasts following cellular stress, injury, repair, as well as during cancer progression. Summary We discuss trends for future studies directed toward the elucidation of gastrin peptides’ role in regulating inter-cellular molecular signaling mechanisms between local and circulating immune cells, fibroblasts, epithelial cells, and other cell-types in the microenvironments of inflammation-related cancers. Elucidation of the molecular and cellular pathways that relate inflammation with cancer may provide additional opportunities to develop complementary therapies that target the inflammatory microenvironment of the cancer. PMID:19907321

  10. Inflammation and metabolic cardiomyopathy.

    PubMed

    Nishida, Kazuhiko; Otsu, Kinya

    2017-03-15

    Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status. Metabolic cardiomyopathy is a chronic metabolic disease characterized by structural and functional alterations and interstitial fibrosis without coronary artery disease or hypertension. In the early stage of metabolic cardiomyopathy, metabolic disturbance is not accompanied by substantial changes in myocardial structure and cardiac function. However, metabolic disturbance induces subcellular low-grade inflammation in the heart, and in turn, subcellular component abnormalities, such as oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and impaired calcium handling, leading to impaired myocardial relaxation. In the advanced stage, the vicious cycle of subcellular component abnormalities, inflammatory cell infiltration, and neurohumoral activation induces cardiomyocyte injury and death, and cardiac fibrosis, resulting in impairment of both diastolic and systolic functions. This review discusses some recent advances in understanding involvement of inflammation in metabolic cardiomyopathy. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  11. Inflammation in Epileptic Encephalopathies.

    PubMed

    Shandra, Oleksii; Moshé, Solomon L; Galanopoulou, Aristea S

    2017-01-01

    West syndrome (WS) is an infantile epileptic encephalopathy that manifests with infantile spasms (IS), hypsarrhythmia (in ~60% of infants), and poor neurodevelopmental outcomes. The etiologies of WS can be structural-metabolic pathologies (~60%), genetic (12%-15%), or of unknown origin. The current treatment options include hormonal treatment (adrenocorticotropic hormone and high-dose steroids) and the GABA aminotransferase inhibitor vigabatrin, while ketogenic diet can be given as add-on treatment in refractory IS. There is a need to identify new therapeutic targets and more effective treatments for WS. Theories about the role of inflammatory pathways in the pathogenesis and treatment of WS have emerged, being supported by both clinical and preclinical data from animal models of WS. Ongoing advances in genetics have revealed numerous genes involved in the pathogenesis of WS, including genes directly or indirectly involved in inflammation. Inflammatory pathways also interact with other signaling pathways implicated in WS, such as the neuroendocrine pathway. Furthermore, seizures may also activate proinflammatory pathways raising the possibility that inflammation can be a consequence of seizures and epileptogenic processes. With this targeted review, we plan to discuss the evidence pro and against the following key questions. Does activation of inflammatory pathways in the brain cause epilepsy in WS and does it contribute to the associated comorbidities and progression? Can activation of certain inflammatory pathways be a compensatory or protective event? Are there interactions between inflammation and the neuroendocrine system that contribute to the pathogenesis of WS? Does activation of brain inflammatory signaling pathways contribute to the transition of WS to Lennox-Gastaut syndrome? Are there any lead candidates or unexplored targets for future therapy development for WS targeting inflammation? © 2017 Elsevier Inc. All rights reserved.

  12. Retroperitoneal inflammation

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001255.htm Retroperitoneal inflammation To use the sharing features on this page, please enable JavaScript. Retroperitoneal inflammation is swelling that occurs in the retroperitoneal space. ...

  13. Anemia of inflammation.

    PubMed

    Nemeth, Elizabeta; Ganz, Tomas

    2014-08-01

    Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. It is diagnosed when serum iron concentrations are low despite adequate iron stores, as evidenced by serum ferritin that is not low. In the setting of inflammation, it may be difficult to differentiate AI from iron deficiency anemia, and the 2 conditions may coexist. Treatment should focus on the underlying disease. Recent advances in molecular understanding of AI are stimulating the development of new pathophysiologically targeted experimental therapies.

  14. Quercetin, Inflammation and Immunity.

    PubMed

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-03-15

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

  15. Quercetin, Inflammation and Immunity

    PubMed Central

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-01-01

    In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

  16. Natural resolution of inflammation.

    PubMed

    Freire, Marcelo O; Van Dyke, Thomas E

    2013-10-01

    Inflammation is a protective response essential for maintaining human health and for fighting disease. As an active innate immune reaction to challenge, inflammation gives rise to clinical cardinal signs: rubor, calor, dolor, tumor and functio laesa. Termination of acute inflammation was previously recognized as a passive process; a natural decay of pro-inflammatory signals. We now understand that the natural resolution of inflammation involves well-integrated, active, biochemical programs that return tissues to homeostasis. This review focuses on recent advances in the understanding of the role of endogenous lipid mediators that modulate cellular fate and inflammation. Biosynthesis of eicosanoids and other lipids in exudates coincides with changes in the types of inflammatory cells. Resolution of inflammation is initiated by an active class switch in lipid mediators, such as classic prostaglandins and leukotrienes, to the production of proresolution mediators. Endogenous pro-resolving lipid mediators, including arachidonic acid-derived lipoxins, aspirin-triggered lipoxins, ω3-eicosapentaenoic acid-derived resolvins of the E-series, docosahexaenoic acid-derived resolvins of the D-series, protectins and maresins, are biosynthesized during the resolution phase of acute inflammation. Depending on the type of injury and the type of tissue, the initial cells that respond are polymorphonuclear leukocytes, monocytes/macrophages, epithelial cells or endothelial cells. The selective interaction of specific lipid mediators with G protein-coupled receptors expressed on innate immune cells (e.g. G protein-coupled receptor 32, lipoxin A4 receptor/formyl peptide receptor2, chemokine-like receptor 1, leukotriene B4 receptor type 1 and cabannoid receptor 2) induces cessation of leukocyte infiltration; vascular permeability/edema returns to normal with polymorphonuclear neutrophil death (mostly via apoptosis), the nonphlogistic infiltration of monocyte/macrophages and the removal

  17. Identification of Novel Inflammatory Cytokines and Contribution of Keratinocyte-Derived Chemokine to Inflammation in Response to Vibrio vulnificus Infection in Mice.

    PubMed

    Liu, Xiao-Fei; Wu, Jing; Wang, Ming-Yi; Chen, Ying-Jian; Cao, Yuan; Hu, Cheng-Jin

    2015-10-01

    Currently, only tumor necrosis factor alpha (TNF-α) and interleukin family cytokines have been found to be elicited in Vibrio vulnificus (V. vulnificus)-infected animal models and humans. However, multiple other cytokines are also involved in the immune and inflammatory responses to foreign microorganism infection. Antibody array technology, unlike traditional enzyme-linked immunosorbent assay (ELISA), is able to detect multiple cytokines at one time. Therefore, in this study, we examined the proinflammatory cytokine profile in the serum and liver homogenate samples of bacterial-infected mice using antibody array technology. We identified nine novel cytokines in response to V. vulnificus infection in mice. We found that keratinocyte-derived chemokine (KC) was the most elevated cytokine and demonstrated that KC played a very important role in the V. vulnificus infection-elicited inflammatory response in mice, as evidenced by the fact that the blocking of KC by anti-KC antibody reduced hepatic injury in vivo and that KC induced by V. vulnificus infection in AML-12 cells chemoattracted neutrophils. Our findings implicate that KC may serve as a novel diagnostic biomarker and a possible therapeutic target for V. vulnificus infection.

  18. Activation of mucosal mast cells promotes inflammation-related colon cancer development through recruiting and modulating inflammatory CD11b(+)Gr1(+) cells.

    PubMed

    Xu, Lingzhi; Yi, Hong-Gan; Wu, Zhiyuan; Han, Wenxiao; Chen, Kun; Zang, Mengya; Wang, Dongmei; Zhao, Xinhua; Wang, Hongying; Qu, Chunfeng

    2015-08-10

    Mast cells (MCs) have been reported to be one of the important immunoregulatory cells in promoting the development of colitis-related colon cancer (CRC). It is not clear which MC subtypes play critical roles in CRC progression from colitis to cancer because mucosal mast cells (MMCs) are distinct from connective tissue mast cells (CTMCs) in maintaining intestinal barrier function under homeostatic and inflammatory conditions. In the current study, we found that MMC numbers and the gene expressions of MMC-specific proteases increased significantly in an induced CRC murine model. The production of mast cell protease-1 (mMCP-1) after MMC activation not only resulted in the accumulation of CD11b(+)Gr1(+) inflammatory cells in the colon tissues but also modulated the activities of CD11b(+)Gr1(+) cells to support tumor cell growth and to inhibit T cell activation. Blocking the MMC activity in mice that had developed colitis-related epithelium dysplasia, CD11b(+)Gr1(+) infiltration was reduced and CRC development was inhibited. Our results suggest that MMC activation recruited and modulated the CD11b(+)Gr1(+) cells to promote CRC and that MMCs can be potential therapeutic targets for the prevention of CRC development.

  19. Regulation of caspase 14 expression in keratinocytes by inflammatory cytokines--a possible link between reduced skin barrier function and inflammation?

    PubMed

    Hvid, Malene; Johansen, Claus; Deleuran, Bent; Kemp, Kaare; Deleuran, Mette; Vestergaard, Christian

    2011-08-01

    Caspase 14 is a unique member of the cysteinyl aspartate-specific proteinase family. Its expression is confined primarily to cornified epithelium such as the skin. Caspase 14 has been associated with the processing of filaggrin monomers and the development of natural moisturising factors of the skin, and thus, it could be speculated that caspase 14 dysregulation is implicated in the development of an impaired skin barrier function. We have investigated the regulation of caspase 14 transcription in cultured primary keratinocytes following stimulation with a number of factors present in inflamed skin, including T(H)1- and T(H)2-associated cytokines in addition to LPS and peptidoglycan. In particular, we found that T(H)2-associated cytokines reduced the caspase 14 mRNA level significantly. Furthermore, we found that the expression of caspase 14 was reduced in skin biopsies from patients with atopic dermatitis (AD), psoriasis and contact dermatitis, further supporting a role for this kinase in inflammatory skin conditions. Hence, the regulation of caspase 14 levels provides a possible link between impaired skin barrier function and inflammatory reactions in skin diseases such as AD and may offer an explanation to the skin barrier dysfunction in inflamed skin lesions.

  20. Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway.

    PubMed

    Ma, Chunhua; Zhu, Lingpeng; Wang, Jing; He, He; Chang, Xiayun; Gao, Jin; Shumin, Wang; Yan, Tianhua

    2015-06-20

    Taraxacum mongolicum Hand.-Mazz is a famous medicinal plant in China, has been listed in the Pharmacopoeia of the People's Republic of China and used to treat infection, fever, upper respiratory tract infection, pneumonia, and other infectious diseases. This study aims to evaluate the possible mechanisms responsible for the anti-inflammation effects of water extract of T. mongolicum Hand.-Mazz (WETMHM) on lipopolysaccharide (LPS)-induced inflammatory in acute lung injury. Female BALB/c mice were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) LPS group, (3) LPS+dexamethasone (LPS+Dex, 2mg/kg, administered by gavage), (4) LPS+WETMHM (5 g/kg, administered by gavage), (5) LPS+WETMHM (10 g/kg, administered by gavage). The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity were assayed by SOD and MPO kits, respectively. The levels of inflammation mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were assayed by an enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed by hematoxylin and eosin (HE) staining. The levels of P-PI3K, PI3K, P-Akt, Akt, P-mTOR and mTOR were measured by Western blotting. The data showed that treatment with the WETMHM inhibited LPS-induced inflammation: (1) WETMHM attenuated inflammation cell numbers in the BALF, (2) decreased protein levels of lung PI3K/Akt/mTOR, and (3) improved SOD activity and (4) inhibited MPO activity; (5) histological studies demonstrated that WETMHM substantially inhibited LPS-induced neutrophils in lung tissue. The results indicated that the WETMHM had a protective effect on LPS-induced ALI in mice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Grass carp TGF-β1 impairs IL-1β signaling in the inflammatory responses: Evidence for the potential of TGF-β1 to antagonize inflammation in fish.

    PubMed

    Wang, Xinyan; Yang, Xiao; Wen, Chao; Gao, Yajun; Qin, Lei; Zhang, Shengnan; Zhang, Anying; Yang, Kun; Zhou, Hong

    2016-06-01

    results to our knowledge provide the first evidence for inducible TGF-β1 expression in inflammatory process, as well as the induction of inflammatory stimuli on IL-1β expression and signaling. In turn, TGF-β1 suppressed the proinflammatory process in vitro and in vivo presumably via interfering IL-1β expression and signaling in inflammatory response, highlighting the potential of TGF-β1 in the control of inflammation in fish.

  2. Eicosanoids in skin inflammation.

    PubMed

    Nicolaou, Anna

    2013-01-01

    Eicosanoids play an integral part in homeostatic mechanisms related to skin health and structural integrity. They also mediate inflammatory events developed in response to environmental factors, such as exposure to ultraviolet radiation, and inflammatory and allergic disorders, including psoriasis and atopic dermatitis. This review article discusses biochemical aspects related to cutaneous eicosanoid metabolism, the contribution of these potent autacoids to skin inflammation and related conditions, and considers the importance of nutritional supplementation with bioactives such as omega-3 and omega-6 polyunsaturated fatty acids and plant-derived antioxidants as means of addressing skin health issues.

  3. Chronic inflammation potentiates kidney aging.

    PubMed

    Mei, Changlin; Zheng, Feng

    2009-11-01

    Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-alpha, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney.

  4. Plain magnetic resonance imaging as an alternative in evaluating inflammation and bowel damage in inflammatory bowel disease--a prospective comparison with conventional magnetic resonance follow-through.

    PubMed

    Jesuratnam-Nielsen, Kayalvily; Løgager, Vibeke B; Rezanavaz-Gheshlagh, Bijan; Munkholm, Pia; Thomsen, Henrik S

    2015-05-01

    To compare prospectively the diagnostic accuracy of magnetic resonance imaging (MRI) without use of contrast medium orally or intravenously (plain MRI) with magnetic resonance follow-through (MRFT) in patients with inflammatory bowel disease (IBD). Plain MRI was carried out in addition to MRFT, to which the patients were referred. All patients underwent both examinations on the same day. For the evaluation, the bowel was divided into nine segments. Two radiologists, blinded to clinical findings, evaluated bowel wall thickness, diffusion weighted imaging (DWI), and other inflammatory changes in each bowel segments. Further, hyperenhancement of the bowel was also evaluated in MRFT. A total of 100 patients (40 males and 60 females; median age: 38.5; range: 19-90) were enrolled; 44 with Crohn's disease (CD), 25 with ulcerative colitis (UC), 24 with IBD unclassified (IBD-U), and 7 had other diagnosis. Sensitivity, specificity, and accuracy in CD ranged 50-86%, 93-94%, and 91-92% for wall thickening and 49-82%, 85-93%, and 84-89% for DWI, respectively. Sensitivity, specificity, and accuracy in UC range 0-40%, 87-100%, and 80-100% for wall thickening and 0-52%, 83-94% and 76-92% for DWI, respectively. The κ values for bowel wall thickening, DWI, and mural hyperenhancement were detected with fair agreement (κ = 0.26-0.39) at both MRI examinations, whereas only bowel wall thickening in MRFT were detected with moderate agreement (κ = 0.47) Conclusion. Plain MRI cannot currently replace MRFT in the workup of patients with IBD. Further research on plain MRI is needed to improve the protocol.

  5. Evolution of Inflammatory Diseases

    PubMed Central

    Okin, Daniel

    2013-01-01

    The association of inflammation with modern human diseases (e.g. obesity, cardiovascular disease, type 2 diabetes mellitus, cancer) remains an unsolved mystery of current biology and medicine. Inflammation is a protective response to noxious stimuli that unavoidably occurs at a cost to normal tissue function. This fundamental tradeoff between the cost and benefit of the inflammatory response has been optimized over evolutionary time for specific environmental conditions. Rapid change of the human environment due to niche construction outpaces genetic adaptation through natural selection, leading increasingly to a mismatch between the modern environment and selected traits. Consequently, multiple tradeoffs that affect human physiology are not optimized to the modern environment, leading to increased disease susceptibility. Here we examine the inflammatory response from an evolutionary perspective. We discuss unique aspects of the inflammatory response and its evolutionary history that can help explain the association between inflammation and modern human diseases. PMID:22975004

  6. Inflammatory mediators in epilepsy.

    PubMed

    Lorigados Pedre, Lourdes; Morales Chacón, Lilia M; Orozco Suárez, Sandra; Pavón Fuentes, Nancy; Estupiñán Díaz, Bárbara; Serrano Sánchez, Teresa; García Maeso, Iván; Rocha Arrieta, Luisa

    2013-01-01

    All common contributing factors to epilepsy such as trauma, malignancies and infections are accompanied by different levels of central nervous system inflammation that in turn have been associated with the occurrence of seizure. Emerging data from human brain tissue and experimental models of epilepsy support the proposed involvement of inflammation in epilepsy. Key mediators of this process include, among others: interleukin (IL) -1β, IL-6, tumor necrosis factor-α, adhesion molecules and component of complement. Recent advances suggest the involvement of specific inflammatory pathways in the pathogenesis of seizures in patients with pharmacoresistant temporal lobe epilepsy, highlighting the potential for new therapeutic strategies. This review provides an overview of the current knowledge on the relationship between inflammatory mediators and epilepsy. We also describe experimental and clinical evidence of inflammation in epilepsy with special emphasis on clinical aspects once the epileptogenic focus has been resected. Further insight into the complex role of inflammation in epileptogenesis may provide new treatment options.

  7. Thermography in ocular inflammation

    PubMed Central

    Kawali, Ankush A

    2013-01-01

    Background and Objectives: The purpose of this study was to evaluate ocular inflammatory and non-inflammatory conditions using commercially available thermal camera. Materials and Methods: A non-contact thermographic camera (FLIR P 620) was used to take thermal pictures of seven cases of ocular inflammation, two cases of non-inflammatory ocular pathology, and one healthy subject with mild refractive error only. Ocular inflammatory cases included five cases of scleritis, one case of postoperative anterior uveitis, and a case of meibomian gland dysfunction with keratitis (MGD-keratitis). Non-inflammatory conditions included a case of conjunctival benign reactive lymphoid hyperplasia (BRLH) and a case of central serous chorio-retinopathy. Thermal and non-thermal photographs were taken, and using analyzing software, the ocular surface temperature was calculated. Results: Patient with fresh episode of scleritis revealed high temperature. Eyes with MGD-keratitis depicted lower temperature in clinically more affected eye. Conjunctival BRLH showed a cold lesion on thermography at the site of involvement, in contrast to cases of scleritis with similar clinical presentation. Conclusion: Ocular thermal imaging is an underutilized diagnostic tool which can be used to distinguish inflammatory ocular conditions from non-inflammatory conditions. It can also be utilized in the evaluation of tear film in dry eye syndrome. Its applications should be further explored in uveitis and other ocular disorders. Dedicated “ocular thermographic” camera is today's need of the hour. PMID:24347863

  8. Hyaluronan, a Crucial Regulator of Inflammation

    PubMed Central

    Petrey, Aaron C.; de la Motte, Carol A.

    2014-01-01

    Hyaluronan (HA), a major component of the extracellular matrix (ECM), plays a key role in regulating inflammation. Inflammation is associated with accumulation and turnover of HA polymers by multiple cell types. Increasingly through the years, HA has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes. HA and its binding proteins regulate the expression of inflammatory genes, the recruitment of inflammatory cells, the release of inflammatory cytokines, and can attenuate the course of inflammation, providing protection against tissue damage. A growing body of evidence suggests the cell responses are HA molecular weight dependent. HA fragments generated by multiple mechanisms throughout the course of inflammatory pathologies, elicit cellular responses distinct from intact HA. This review focuses on the role of HA in the promotion and resolution of inflammation. PMID:24653726

  9. Inflammation and colon cancer.

    PubMed

    Terzić, Janos; Grivennikov, Sergei; Karin, Eliad; Karin, Michael

    2010-06-01

    The connection between inflammation and tumorigenesis is well-established and in the last decade has received a great deal of supporting evidence from genetic, pharmacological, and epidemiological data. Inflammatory bowel disease is an important risk factor for the development of colon cancer. Inflammation is also likely to be involved with other forms of sporadic as well as heritable colon cancer. The molecular mechanisms by which inflammation promotes cancer development are still being uncovered and could differ between colitis-associated and other forms of colorectal cancer. Recent work has elucidated the role of distinct immune cells, cytokines, and other immune mediators in virtually all steps of colon tumorigenesis, including initiation, promotion, progression, and metastasis. These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review.

  10. Cancer-related inflammation.

    PubMed

    Candido, Juliana; Hagemann, Thorsten

    2013-01-01

    Solid tumors consist of neoplastic cells, non-malignant stromal cells, and migratory hematopoietic cells. Complex interactions between the cell types in this microenvironment regulate tumor growth, progression, metastasis, and angiogenesis. The cells and mediators of inflammation form a major part of the epithelial tumor microenvironment. In some cancers, inflammatory conditions precede development of malignancy; in others, oncogenic change drives a tumor-promoting inflammatory milieu. Whatever its origin, this "smoldering" inflammation aids proliferation and survival of malignant cells, stimulates angiogenesis and metastasis, subverts adaptive immunity, and alters response to hormones and chemotherapy. Cytokines are major mediators of communication between cells in the inflammatory tumor microenvironment. It is known that neoplastic cells often over-express proinflammatory mediators including proteases, eicosanoids, cytokines, and chemokines. Several cytokines such as macrophage migratory inhibitory factor (MIF), TNF-α, IL-6, IL-17, IL-12, IL-23, IL-10, and TGF-β have been linked with both experimental and human cancers and can either promote or inhibit tumor development. MIF is a major cytokine in many cancers and there is evidence that the cytokine is produced by both malignant cells and infiltrating leukocytes. In this article we will discuss the role of cancer-associated inflammation and the particular role of MIF in malignant disease.

  11. Ion channels in inflammation.

    PubMed

    Eisenhut, Michael; Wallace, Helen

    2011-04-01

    Most physical illness in vertebrates involves inflammation. Inflammation causes disease by fluid shifts across cell membranes and cell layers, changes in muscle function and generation of pain. These disease processes can be explained by changes in numbers or function of ion channels. Changes in ion channels have been detected in diarrhoeal illnesses, pyelonephritis, allergy, acute lung injury and systemic inflammatory response syndromes involving septic shock. The key role played by changes in ion transport is directly evident in inflammation-induced pain. Expression or function of all major categories of ion channels like sodium, chloride, calcium, potassium, transient receptor potential, purinergic receptor and acid-sensing ion channels can be influenced by cyto- and chemokines, prostaglandins, leukotrienes, histamine, ATP, reactive oxygen species and protons released in inflammation. Key pathways in this interaction are cyclic nucleotide, phosphoinositide and mitogen-activated protein kinase-mediated signalling, direct modification by reactive oxygen species like nitric oxide, ATP or protons and disruption of the cytoskeleton. Therapeutic interventions to modulate the adverse and overlapping effects of the numerous different inflammatory mediators on each ion transport system need to target adversely affected ion transport systems directly and locally.

  12. Therapeutic Evaluation of Mesenchymal Stem Cells in Chronic Gut Inflammation

    DTIC Science & Technology

    2015-09-01

    IL-10, TGFβ; colitis; intestinal inflammation; immunosuppression 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES...inflammatory bowel disease; mesenchymal stem cells; Tregs; IL-10, TGFβ; colitis; intestinal inflammation; immuno-suppression; 3. ACCOMPLISHMENTS Major Goals

  13. Mitigation of inflammation with foods.

    PubMed

    Wu, Xianli; Schauss, Alexander G

    2012-07-11

    Constant overproduction of pro-inflammatory molecules leads to chronic inflammation. Unlike acute inflammation, which is essential for healing, chronic inflammation can delay healing and, if left unchecked, contribute to a host of diseases. There is growing evidence that some dietary factors can play important roles in maintaining health and even reversing the progression of chronic diseases, with anti-inflammatory effects as important underlying mechanism. Such findings add to the body of evidence that certain dietary components, including polyphenols and other types of compounds, found in various dietary factors including fruits, berries, vegetables, nuts, whole grains, and foods of marine origin, can play an important role in attenuating and mitigating chronic pro-inflammatory processes associated with chronic diseases.

  14. Parkinson's disease and systemic inflammation.

    PubMed

    Ferrari, Carina C; Tarelli, Rodolfo

    2011-02-22

    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the "primed" microglia into an "active" state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease.

  15. Parkinson's Disease and Systemic Inflammation

    PubMed Central

    Ferrari, Carina C.; Tarelli, Rodolfo

    2011-01-01

    Peripheral inflammation triggers exacerbation in the central brain's ongoing damage in several neurodegenerative diseases. Systemic inflammatory stimulus induce a general response known as sickness behaviour, indicating that a peripheral stimulus can induce the synthesis of cytokines in the brain. In Parkinson's disease (PD), inflammation was mainly associated with microglia activation that can underlie the neurodegeneration of neurons in the substantia nigra (SN). Peripheral inflammation can transform the “primed” microglia into an “active” state, which can trigger stronger responses dealing with neurodegenerative processes. Numerous evidences show that systemic inflammatory processes exacerbate ongoing neurodegeneration in PD patient and animal models. Anti-inflammatory treatment in PD patients exerts a neuroprotective effect. In the present paper, we analyse the effect of peripheral infections in the etiology and progression in PD patients and animal models, suggesting that these peripheral immune challenges can exacerbate the symptoms in the disease. PMID:21403862

  16. 99th Dahlem Conference on Infection, Inflammation and Chronic Inflammatory Disorders: Immune therapies of type 1 diabetes: new opportunities based on the hygiene hypothesis

    PubMed Central

    Chatenoud, L; You, S; Okada, H; Kuhn, C; Michaud, B; Bach, J-F

    2010-01-01

    Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting β cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4+ and CD8+ T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the ‘hygiene hypothesis’, which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically. PMID:20415859

  17. Calprotectin Is a Useful Tool in Distinguishing Coexisting Irritable Bowel-Like Symptoms from That of Occult Inflammation among Inflammatory Bowel Disease Patients in Remission

    PubMed Central

    Jelsness-Jørgensen, Lars-Petter; Bernklev, Tomm; Moum, Bjørn

    2013-01-01

    Background and Aim. In the inflammatory bowel diseases (IBDs), many symptoms are similar to the functional disorder irritable bowel syndrome (IBS). A challenge is thus to distinguish symptoms of IBD from IBS. The aim of this study was to investigate the levels of calprotectin in IBS-positive IBD patients in remission. Methods. Remission was defined as a simple clinical colitis activity index (SCCAI) or simple crohn's disease activity index (SCDAI) score of less than three and less than four, respectively. The Rome II criteria were used to identify cases, and the calprotectin ELISA test was used to quantify calprotectin in stools. Results. The Rome II criteria were fulfilled in 24.6% of ulcerative colitis (UC) patients, while the comparable number for Crohn's disease (CD) was 21.4%. There was a tendency for elevated fecal calprotectin levels in IBS-positive patients, regardless of diagnosis. However, these differences were only significant in CD. Conclusions. Calprotectin levels are elevated in subgroups of IBD patients that are in remission and have coexisting IBS-like symptoms. This study underscores the clinical usefulness of a noninvasive marker to distinguish patients in need of intensified followup from those that do not need further workup. PMID:23476638

  18. Inflammation in diabetic kidney disease

    PubMed Central

    García-García, Patricia M; Getino-Melián, María A; Domínguez-Pimentel, Virginia; Navarro-González, Juan F

    2014-01-01

    Diabetes mellitus entails significant health problems worldwide. The pathogenesis of diabetes is multifactorial, resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events, with metabolic and hemodynamic alterations. In this context, inflammation has emerged as a key pathophysiology mechanism. New pathogenic pathways will provide targets for prevention or future treatments. This review will focus on the implications of inflammation in diabetes mellitus, with special attention to inflammatory cytokines. PMID:25126391

  19. Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS).

    PubMed

    Polizzotto, Mark N; Uldrick, Thomas S; Wyvill, Kathleen M; Aleman, Karen; Marshall, Vickie; Wang, Victoria; Whitby, Denise; Pittaluga, Stefania; Jaffe, Elaine S; Millo, Corina; Tosato, Giovanna; Little, Richard F; Steinberg, Seth M; Sereti, Irini; Yarchoan, Robert

    2016-03-15

    Kaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory cytokine syndrome (KICS) distinct from KSHV-MCD was reported. We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection. All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50-74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6-11), median grade of worst symptom 3 (2-4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death. KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  20. Clinical Features and Outcomes of Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV)-associated Inflammation: Prospective Characterization of KSHV Inflammatory Cytokine Syndrome (KICS)

    PubMed Central

    Polizzotto, Mark N.; Uldrick, Thomas S.; Wyvill, Kathleen M.; Aleman, Karen; Marshall, Vickie; Wang, Victoria; Whitby, Denise; Pittaluga, Stefania; Jaffe, Elaine S.; Millo, Corina; Tosato, Giovanna; Little, Richard F.; Steinberg, Seth M.; Sereti, Irini; Yarchoan, Robert

    2016-01-01

    Background. Kaposi sarcoma herpesvirus (KSHV) is the cause of Kaposi sarcoma (KS), primary effusion lymphoma (PEL), and a form of Castleman disease (KSHV-MCD). Recently a KSHV-associated inflammatory cytokine syndrome (KICS) distinct from KSHV-MCD was reported. Methods. We prospectively characterized the clinical, laboratory, virologic and immunologic features of KICS by evaluating symptomatic adults with KSHV using a prespecified definition. These features and overall survival were compared with controls from 2 prospectively characterized human immunodeficiency virus (HIV)-infected cohorts, including 1 with KSHV coinfection. Results. All 10 KICS subjects were HIV infected males; 5 had HIV viral load (VL) suppressed <50 copies mL (median 72, range <50–74 375); all had KS and 2 also had PEL. All had multiple severe symptoms attributable to KICS: median number of symptoms 8 (6–11), median grade of worst symptom 3 (2–4). These included gastrointestinal disturbance (present in 9); edema (9); respiratory (6); and effusions (5). Laboratory abnormalities included anemia (all); hypoalbuminemia (all) and thrombocytopenia (6). None developed KSHV-MCD; 6 died with median survival from KICS diagnosis 13.6 months. KICS subjects compared with controls had more severe symptoms; lower hemoglobin and albumin; higher C-reactive protein; higher KSHV VL; elevated interleukin (IL)-6 and IL-10; and an increased risk of death (all P < .05). Anemia and hypoalbuminemia at presentation were independently associated with early death. Conclusions. KICS subjects demonstrated diverse severe symptoms, a high rate of KSHV-associated tumors, high mortality, and a distinct IL-6/IL-10 signature. KICS may be an important unrecognized cause of morbidity and mortality, including symptoms previously ascribed to HIV. Exploration of KSHV-directed therapy is warranted. PMID:26658701

  1. Surgical inflammation: a pathophysiological rainbow

    PubMed Central

    Arias, Jose-Ignacio; Aller, María-Angeles; Arias, Jaime

    2009-01-01

    Tetrapyrrole molecules are distributed in virtually all living organisms on Earth. In mammals, tetrapyrrole end products are closely linked to oxygen metabolism. Since increasingly complex trophic functional systems for using oxygen are considered in the post-traumatic inflammatory response, it can be suggested that tetrapyrrole molecules and, particularly their derived pigments, play a key role in modulating inflammation. In this way, the diverse colorfulness that the inflammatory response triggers during its evolution would reflect the major pathophysiological importance of these pigments in each one of its phases. Therefore, the need of exploiting this color resource could be considered for both the diagnosis and treatment of the inflammation. PMID:19309494

  2. Oral inflammation in small animals.

    PubMed

    Lommer, Milinda J

    2013-05-01

    The oral cavity can be affected by a wide variety of disorders characterized by inflammation of the gingiva and/or oral mucosa. In dogs and cats, differential diagnoses for generalized oral inflammatory disorders include plaque-reactive mucositis, chronic gingivostomatitis, eosinophilic granuloma complex, pemphigus and pemphigoid disorders, erythema multiforme, and systemic lupus erythematosus. In addition, endodontic or periodontal abscesses, infectious conditions, reactive lesions, and neoplastic conditions may initially present with localized or generalized inflammation of the oral mucosa. Determination of the underlying cause of an oral inflammatory condition relies on a thorough history, complete physical and oral examination, and incisional biopsy and histopathologic examination of lesions.

  3. Inflammation in Diabetic Retinopathy

    PubMed Central

    Tang, Johnny; Kern, Timothy S.

    2012-01-01

    Diabetes causes a number of metabolic and physiologic abnormalities in the retina, but which of these abnormalities contribute to recognized features of diabetic retinopathy (DR) is less clear. Many of the molecular and physiologic abnormalities that have been found to develop in the retina in diabetes are consistent with inflammation. Moreover, a number of anti-inflammatory therapies have been found to significantly inhibit development of different aspects of DR in animal models. Herein, we review the inflammatory mediators and their relationship to early and late DR, and discuss the potential of anti-inflammatory approaches to inhibit development of different stages of the retinopathy. We focus primarily on information derived from in vivo studies, supplementing with information from in vitro studies were important. PMID:21635964

  4. Curcumin in inflammatory diseases.

    PubMed

    Shehzad, Adeeb; Rehman, Gauhar; Lee, Young Sup

    2013-01-01

    Curcumin (diferuloylmethane), a yellow coloring agent extracted from turmeric is also used as a remedy for the treatment and prevention of inflammatory diseases. Acute and chronic inflammation is a major factor in the progression of obesity, type II diabetes, arthritis, pancreatitis, cardiovascular, neurodegenerative and metabolic diseases, as well as certain types of cancer. Turmeric has a long history of use in Ayurvedic medicine for the treatment of inflammatory disorders. Recent studies on the efficacy and therapeutic applicability of turmeric have suggested that the active ingredient of tumeric is curcumin. Further, compelling evidence has shown that curcumin has the ability to inhibit inflammatory cell proliferation, invasion, and angiogenesis through multiple molecular targets and mechanisms of action. Curcumin is safe, non-toxic, and mediates its anti-inflammatory effects through the down-regulation of inflammatory transcription factors, cytokines, redox status, protein kinases, and enzymes that all promote inflammation. In addition, curcumin induces apoptosis through mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the current study, the anti-inflammatory effects of curcumin were evaluated relative to various chronic inflammatory diseases. Based on the available pharmacological data obtained from in vitro and in vivo research, as well as clinical trials, an opportunity exists to translate curcumin into clinics for the prevention of inflammatory diseases in the near future.

  5. Inflammation in the early stages of neurodegenerative pathology

    PubMed Central

    Khandelwal, Preeti J.; Herman, Alexander M.; Moussa, Charbel E-H

    2011-01-01

    Inflammation is secondary to protein accumulation in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Amyotrophic Lateral Sclerosis. Emerging evidence indicate sustained inflammatory responses, involving microglia and astrocytes in animal models of neurodegeneration. It is unknown whether inflammation is beneficial or detrimental to disease progression and how inflammatory responses are induced within the CNS. Persistence of an inflammatory stimulus or failure to resolve sustained inflammation can result in pathology, thus, mechanisms that counteract inflammation are indispensable. Here we review studies on inflammation mediated by innate and adaptive immunity in the early stages of neurodegeneration and highlight important areas for future investigation. PMID:21820744

  6. Models of inflammation: carrageenan air pouch.

    PubMed

    Duarte, Djane B; Vasko, Michael R; Fehrenbacher, Jill C

    2012-03-01

    The subcutaneous air pouch is an in vivo model that can be used to study acute and chronic inflammation, the resolution of the inflammatory response, and the oxidative stress response. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.

  7. Endogenous Inhibitors of Kidney Inflammation

    PubMed Central

    Trostel, Jessica; Garcia, Gabriela E.

    2015-01-01

    Although inflammation is the physiological response to pathogen invasion and tissue damage, it can also be responsible for significant tissue damage. Therefore, the inflammatory response must be carefully regulated to prevent critical inflammatory damage to vital organs. Typically, local endogenous regulatory mechanisms adjust the magnitude of the response such that the injurious condition is resolved and homeostasis is mantained. Humoral mechanisms that restrain or inhibit inflammation include glucocorticoid hormones, anti-inflammatory cytokines such as IL-10 and transforming growth factor-β (TGF-β), and soluble cytokine receptors; other mediators facilitate tissue healing, like lipoxins and resolvins. There is growing evidence that inflammation plays a critical role in the development and progression of heart disease, cancer, stroke, diabetes, kidney diseases, sepsis, and several fibroproliferative disorders. Consequently, understanding the mechanisms that regulate inflammation may offer therapeutic targets for inhibiting the progression of several diseases. In this article, we review the significance of several novel endogenous anti-inflammatory mediators in the protection from kidney injury and the potential of these regulatory molecules as therapeutic targets for treatment of kidney inflammatory diseases. PMID:26779569

  8. Mechanisms Underlying Inflammation in Neurodegeneration

    PubMed Central

    Glass, Christopher K.; Saijo, Kaoru; Winner, Beate; Marchetto, Maria Carolina; Gage, Fred H.

    2010-01-01

    Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner, there is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators. A major unanswered question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. PMID:20303880

  9. Models of Inflammation: Carrageenan Air Pouch.

    PubMed

    Duarte, Djane B; Vasko, Michael R; Fehrenbacher, Jill C

    2016-03-18

    The subcutaneous air pouch is an in vivo model that can be used to study the components of acute and chronic inflammation, the resolution of the inflammatory response, the oxidative stress response, and potential therapeutic targets for treating inflammation. Injection of irritants into an air pouch in rats or mice induces an inflammatory response that can be quantified by the volume of exudate produced, the infiltration of cells, and the release of inflammatory mediators. The model presented in this unit has been extensively used to identify potential anti-inflammatory drugs.

  10. Macrophages in Synovial Inflammation

    PubMed Central

    Kennedy, Aisling; Fearon, Ursula; Veale, Douglas J.; Godson, Catherine

    2011-01-01

    Synovial macrophages are one of the resident cell types in synovial tissue and while they remain relatively quiescent in the healthy joint, they become activated in the inflamed joint and, along with infiltrating monocytes/macrophages, regulate secretion of pro-inflammatory cytokines and enzymes involved in driving the inflammatory response and joint destruction. Synovial macrophages are positioned throughout the sub-lining layer and lining layer at the cartilage–pannus junction and mediate articular destruction. Sub-lining macrophages are now also considered as the most reliable biomarker for disease severity and response to therapy in rheumatoid arthritis (RA). There is a growing understanding of the molecular drivers of inflammation and an appreciation that the resolution of inflammation is an active process rather than a passive return to homeostasis, and this has implications for our understanding of the role of macrophages in inflammation. Macrophage phenotype determines the cytokine secretion profile and tissue destruction capabilities of these cells. Whereas inflammatory synovial macrophages have not yet been classified into one phenotype or another it is widely known that TNFα and IL-l, characteristically released by M1 macrophages, are abundant in RA while IL-10 activity, characteristic of M2 macrophages, is somewhat diminished. Here we will briefly review our current understanding of macrophages and macrophage polarization in RA as well as the elements implicated in controlling polarization, such as cytokines and transcription factors like NFκB, IRFs and NR4A, and pro-resolving factors, such as LXA4 and other lipid mediators which may promote a non-inflammatory, pro-resolving phenotype, and may represent a novel therapeutic paradigm. PMID:22566842

  11. [Auto-inflammatory syndromes].

    PubMed

    Grateau, Gilles

    2005-02-28

    Auto-inflammatory syndromes are a group of hereditary diseases characterised by intermittent bouts of clinical inflammation with focal organ involvement mainly: abdomen, musculoskeletal system and skin. The most frequent is familial Mediterranean fever, which affects patients of Mediterranean descent all over the world. Three other types have been recently clinically as well as genetically characterised. A thorough diagnosis is warranted, as clinical and therapeutic management is specific for each of these diseases, as underlied by a specific inflammatory pathway. This new group of diseases has already opened new avenues in our understanding of the inflammatory response.

  12. Prostate cancer and inflammation: the evidence

    PubMed Central

    Sfanos, Karen S; De Marzo, Angelo M

    2014-01-01

    Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic noninfectious inflammatory diseases and / or other environmental factors. Indeed, chronic inflammation is now regarded as an ‘enabling characteristic’ of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other antiinflammatory compounds in reducing prostate cancer risk. PMID:22212087

  13. Chemical mediators of inflammation and immunity

    SciTech Connect

    Cohen, S.; Hayashi, H.; Saito, K.; Takada, A.

    1986-01-01

    This book contains five sections, each consisting of several papers. The section tiles are: Activation of Inflammatory Cells, Mechanisms of Tissue Injury, Mechanisms of Lymphocyte Activation, Lympokines and Related Factors, and Mechanisms of Granulomatous Inflammation.

  14. Inflammation and Parkinson's disease.

    PubMed

    Wersinger, Christophe; Sidhu, Anita

    2002-09-01

    Numerous recent findings indicate the possible involvement of an immune mechanism in the pathogenesis of neurodegeneration. The immune reaction could either act as a primary event, generating changes leading to cell death, or could be a secondary response to neuronal injury. In various neurodegenerative disorders such as Alzheimer's, Huntington's or Pick's disease, Down's syndrome, multiple sclerosis and the AIDS-dementia complex, the inflammatory pathomechanism is strongly supported by experimental and clinical studies. Such inflammatory mechanisms have also been postulated in Parkinson's disease (PD). This review summarizes some generalities about inflammation and immune reactions in the context of the brain, and provides clinical, epidemiological and experimental data showing that inflammation and immunity, or even auto-immunity, could be implicated in PD, either in its initial step or in its progression. Different experimental models useful for studying the role(s) of inflammation and (auto)immunity in the neurodegenerative process of the dopaminergic neurons in PD are examined. The major similarities and differences between PD and other neurodegenerative disorders are discussed.

  15. Inhibiting inflammatory cytokines.

    PubMed

    Kluth, D C; Rees, A J

    1996-11-01

    Acute glomerulonephritis is a common cause of renal dysfunction and ultimately renal failure. The inflammation involved is a tightly regulated response with pro- and anti-inflammatory cytokines playing key roles. Interleukin-1 (IL-1) and tumor necrosis factor (TNF) are the principal pro-inflammatory cytokines produced by intrinsic cells and infiltrating leukocytes. IL-1 and TNF can be directly antagonized using IL-1 receptor antagonist (IL-1ra) or binding proteins such as soluble receptors or antibodies. Alternatively, cytokines with anti-inflammatory properties can be used to decrease IL-1 and TNF synthesis, increase the production of their natural antagonists and deactivate inflammatory cells such as macrophages. This review will focus on these anti-inflammatory cytokines, principally IL-4, IL-6, IL-10 and IL-13, and highlight recent research of their activities in existing models of renal disease. The results of these experiments offer a promising new avenue of treatment.

  16. Transient infection of the zebrafish notochord with E. coli induces chronic inflammation

    PubMed Central

    Nguyen-Chi, Mai; Phan, Quang Tien; Gonzalez, Catherine; Dubremetz, Jean-François; Levraud, Jean-Pierre; Lutfalla, Georges

    2014-01-01

    Zebrafish embryos and larvae are now well-established models in which to study infectious diseases. Infections with non-pathogenic Gram-negative Escherichia coli induce a strong and reproducible inflammatory response. Here, we study the cellular response of zebrafish larvae when E. coli bacteria are injected into the notochord and describe the effects. First, we provide direct evidence that the notochord is a unique organ that is inaccessible to leukocytes (macrophages and neutrophils) during the early stages of inflammation. Second, we show that notochord infection induces a host response that is characterised by rapid clearance of the bacteria, strong leukocyte recruitment around the notochord and prolonged inflammation that lasts several days after bacteria clearance. During this inflammatory response, il1b is first expressed in macrophages and subsequently at high levels in neutrophils. Moreover, knock down of il1b alters the recruitment of neutrophils to the notochord, demonstrating the important role of this cytokine in the maintenance of inflammation in the notochord. Eventually, infection of the notochord induces severe defects of the notochord that correlate with neutrophil degranulation occurring around this tissue. This is the first in vivo evidence that neutrophils can degranulate in the absence of a direct encounter with a pathogen. Persistent inflammation, neutrophil infiltration and restructuring of the extracellular matrix are defects that resemble those seen in bone infection and in some chondropathies. As the notochord is a transient embryonic structure that is closely related to cartilage and bone and that contributes to vertebral column formation, we propose infection of the notochord in zebrafish larvae as a new model to study the cellular and molecular mechanisms underlying cartilage and bone inflammation. PMID:24973754

  17. Inflammation: Friend or foe for animal production?

    USDA-ARS?s Scientific Manuscript database

    Inflammation is an essential immune response that seeks to contain microbial infection and repair damaged tissue. Increased pro-inflammatory mediators have been associated with enhanced resistance to a range of important poultry and pig pathogens. However, inflammation may also have undesirable co...

  18. Purinergic receptors in ocular inflammation.

    PubMed

    Guzman-Aranguez, Ana; Gasull, Xavier; Diebold, Yolanda; Pintor, Jesús

    2014-01-01

    Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly "tuned," can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  19. Purinergic Receptors in Ocular Inflammation

    PubMed Central

    Guzman-Aranguez, Ana; Gasull, Xavier; Diebold, Yolanda; Pintor, Jesús

    2014-01-01

    Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly “tuned,” can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P1,P4-diadenosine tetraphosphate (Ap4A), and P1,P5-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N6-(3-iodobenzyl)-5′-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation. PMID:25132732

  20. Immunogenetics of ocular inflammatory disease.

    PubMed

    Levinson, R D

    2007-02-01

    Ocular inflammatory disease comprises of a diverse group of clinical entities that may result from autoimmune processes, infections, or both. While many individual ocular inflammatory diseases are quite rare, ocular inflammation is one of the more common causes of visual disability, including blindness, in the developed world. Better understanding of ocular inflammatory disease is an important step in designing more sophisticated therapies that may help prevent loss of visual function for these patients.

  1. Unfulfilled inflammatory resolution leads to chronic inflammatory diseases.

    PubMed

    Musk, Philip

    2004-06-01

    Extract: Inflammatory conditions, particularly those that involve chronic inflammation, represent an area of great interest to the pharmaceutical industry. Regulated as they are by a diverse array of ligand-receptor interactions, inflammatory responses are amenable to small molecule pharmaceutical intervention and a wide variety of anti-histamines and anti-inflammatory treatments. Both steroidal and non-steroidal treatments have been developed to treat pro-inflammatory conditions. In their review, Gilroy et al. (2004) present the case for developing novel anti-inflammatory drugs not by finding more effective inhibitors of the inflammatory response, but by developing small molecule drugs that positively regulate the processes and mechanisms by which inflammatory responses are attenuated (i.e., the little known process of inflammatory resolution).

  2. Inflammation, Immunity, and Hypertension.

    PubMed

    Agita, Arisya; Alsagaff, M Thaha

    2017-04-01

    The immune system, inflammation and hypertension are related to each other. Innate and adaptive immunity system triggers an inflammatory process, in which blood pressure may increase, stimulating organ damage. Cells in innate immune system produce ROS, such as superoxide and hydrogen peroxide, which aimed at killing pathogens. Long-term inflammation process increases ROS production, causing oxidative stress which leads to endothelial dysfunction. Endothelial function is to regulate blood vessel tone and structure. When inflammation lasts, NO bioavailability decreases, disrupting its main function as vasodilator, so that blood vessels relaxation and vasodilatation are absent. Effector T cells and regulatory lymphocytes, part of the adaptive immune system, plays role in blood vessels constriction in hypertension. Signals from central nervous system and APC activates effector T lymphocyte differentiation and accelerate through Th-1 and Th-17 phenotypes. Th-1 and Th-17 effectors participate in inflammation which leads to increased blood pressure. One part of CD4+ is the regulatory T cells (Tregs) that suppress immune response activation as they produce immunosuppressive cytokines, such as TGF-β and IL-10. Adoptive transfer of Tregs cells can reduce oxidative stress in blood vessels, endothelial dysfunction, infiltration of aortic macrophages and T cells as well as proinflammatory cytokine levels in plasma circulation.

  3. Gut Microbiota and Inflammation

    PubMed Central

    Hakansson, Asa; Molin, Goran

    2011-01-01

    Systemic and local inflammation in relation to the resident microbiota of the human gastro-intestinal (GI) tract and administration of probiotics are the main themes of the present review. The dominating taxa of the human GI tract and their potential for aggravating or suppressing inflammation are described. The review focuses on human trials with probiotics and does not include in vitro studies a