Science.gov

Sample records for inflammation resembling inflammatory

  1. 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

  2. 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

  3. Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cottenie, Ellen; Menezes, Manoj P; Rossor, Alexander M; Morrow, Jasper M; Yousry, Tarek A; Dick, David J; Anderson, Janice R; Jaunmuktane, Zane; Brandner, Sebastian; Blake, Julian C; Houlden, Henry; Reilly, Mary M

    2013-05-01

    Charcot-Marie-Tooth disease type 4J (CMT4J), a rare form of demyelinating CMT, caused by recessive mutations in the phosphoinositide phosphatase FIG4 gene, is characterised by progressive proximal and distal weakness and evidence of chronic denervation in both proximal and distal muscles. We describe a patient with a previous diagnosis of CMT1 who presented with a two year history of rapidly progressive weakness in a single limb, resembling an acquired inflammatory neuropathy. Nerve conduction studies showed an asymmetrical demyelinating neuropathy with conduction block and temporal dispersion. FIG4 sequencing identified a compound heterozygous I41T/K278YfsX5 genotype. CMT4J secondary to FIG4 mutations should be added to the list of inherited neuropathies that need to be considered in suspected cases of inflammatory demyelinating neuropathy, especially if there is a background history of a more slowly progressive neuropathy.

  4. The Effect of Dietary Intake on Inflammation and Inflammatory Biomarkers

    NASA Technical Reports Server (NTRS)

    Cailliau, Allison

    2016-01-01

    Within the Human Health and Performance Directorate at the NASA Johnson Space Center, it is the responsibility of the Nutritional Biochemistry Laboratory to determine nutrient requirements and research the role of nutrition as a potential countermeasure to the negative effects of spaceflight on human physiology. As a part of the lab, the goal of my project was to determine if and how diet affects inflammation and immune system function during spaceflight. This project involved analysis of both dietary and biochemical data from 20 participants in a prior bed rest study as well as from 17 subjects' flight data. Specifically, I evaluated how the dietary inflammatory index (DII), a calculated estimate, compared to a set of immune and inflammatory blood and urine biomarkers. Comparing DII score and biomarkers helps to determine how intake of certain diet patterns influences inflammation in the body. My project will evaluate the effectiveness of this tool for use in the spaceflight analog bed rest.

  5. 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

  6. [Papillary renal cell carcinoma surrounded by unusual fibrotic reaction resembling inflammatory pseudotumour--a case report].

    PubMed

    Hes, O; Hora, M; Havlícek, F; Chudácek, Z; Klecka, J; Michal, M

    2004-07-01

    Authors report clinicopathological features of an unusual case of composite renal lesion occuring in 32-year-old Caucasian male. The patient was followed for cystic lesion of retroperitoneal-renal region for 5 years. He was indicated for resection of the cystic lesion because of changes of the retroperitoneal mass on CT scan. A cyst was located on upper renal pole. A huge cystic mass filled mainly by necrotic material was resected and submitted for histological examination. The wall of the cyst was composed of fibrous tissue, indistinguishable from inflammatory pseudotumor on histological level. The vital intracystic tissue was formed by well-differentiated papillary renal cell carcinoma. The most important step within differential diagnosis is distinguishing of sarcomatoid differentiation in renal cell carcinoma. This very rare case demonstrates the importance of careful examination of all spindle cell lesions of the kidney.

  7. From Inflammation to Cancer in Inflammatory Bowel Disease: Molecular Perspectives.

    PubMed

    Romano, Maurizio; DE Francesco, Francesco; Zarantonello, Laura; Ruffolo, Cesare; Ferraro, Giuseppe A; Zanus, Giacomo; Giordano, Antonio; Bassi, Nicolò; Cillo, Umberto

    2016-04-01

    Inflammatory bowel diseases (IBD) are associated with an increased risk of colitis-associated colorectal carcinoma (CAC). CAC is one of the most important causes of morbidity and mortality in patients with Crohn's disease and ulcerative colitis. The aim of the present review was to discuss the most important signaling pathways and genetic alterations involved in carcinogenesis related to IBD, focusing on the molecular aspects of cancer stem cell physiology and the impact of the inflammatory microenvironment. Molecular mechanisms involved in CAC development differ from those in sporadic colorectal cancer, reflecting the prominent role of inflammation-induced carcinogenesis in the development of CAC. The alteration of the physiological microenvironment is thought to be responsible for the initiation of carcinogenesis in IBD. Furthermore, cancer stem cells seem to have a fundamental role in the generation and growth of CAC. We also address prevention and treatment modalities of CAC and its involvement in IBD. PMID:27069120

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

    PubMed

    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

    2013-09-01

    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.

  9. 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.

  10. 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. PMID:26915929

  11. Placental inflammation is not increased in inflammatory bowel disease

    PubMed Central

    Taleban, Sasha; Gundogan, Fusun; Chien, Edward K.; Degli-Esposti, Silvia; Saha, Sumona

    2015-01-01

    Background Women with inflammatory bowel disease (IBD) are at increased risk for adverse birth outcomes such as preterm delivery and small for gestational age (SGA) infants. Most recognized cases of fetal growth restriction in singleton pregnancies have underlying placental causes. However, studies in IBD examining poor birth outcomes have focused on maternal factors. We examined whether women with IBD have a higher rate of placental inflammation than non-IBD controls. Methods Between 2008 and 2011, the placental tissue of 7 ulcerative colitis, 5 Crohn’s disease, and 2 IBD-unclassified subjects enrolled in the Pregnancy in Inflammatory Bowel Disease and Neonatal Outcome (PIANO) registry were evaluated for villitis, deciduitis, and chorioamnionitis with/without a fetal inflammatory response. The history and birth outcomes of all IBD subjects were reviewed and matched to 26 non-IBD controls by gestational age at delivery. Results Of women with IBD, 29% delivered preterm infants and 21% delivered SGA infants. Half of the IBD patients had mild-moderate disease flares during pregnancy. Five (36%) patients required corticosteroids, 2 (14%) were maintained on an immunomodulator, and 3 (21%) others received tumor necrosis factor-alpha inhibitors during their pregnancy. Chorioamnionitis was the only identified placental pathology present in the placentas reviewed, occurring less frequently in cases compared to controls (7% vs. 27%, P=0.32). Conclusions Placental inflammatory activation does not appear to be responsible for the increase in adverse birth outcome in women with IBD. Further studies are necessary to validate these findings in IBD to explain poor birth outcomes. PMID:26423206

  12. Apoptosis and Inflammation: Role of Adipokines in Inflammatory Bowel Disease

    PubMed Central

    Ponemone, Venkatesh; Keshavarzian, Ali; Brand, Marc I; Saclarides, Theodore; Abcarian, Herand; Cabay, Robert J; Fletcher, Emma; Larsen, Bianca; Durstine, Larry J; Fantuzzi, Giamila; Fayad, Raja

    2010-01-01

    OBJECTIVES: Leptin and adiponectin (APN) are adipokines produced by adipocytes that participate in the modulation of immune and inflammatory responses. In Crohn's disease (CD), fat wrapping surrounding the inflamed intestine produces high levels of leptin and APN. In inflammatory bowel disease (IBD), apoptosis resistance of lamina propria T lymphocytes (LPL-T) is one of the mechanisms that maintains chronic inflammation. We addressed the mechanism by which leptin and APN regulate inflammation and apoptosis in IBD. METHODS: Immune cell infiltration, several factors expressed by adipose tissue (AT), and spontaneous release of cytokines by adipocytes were measured. The presence of APN and leptin in intestinal mucosa was detected and their effect on LPL-T apoptosis, signal transducer and activator of transcription 3 (STAT3), Suppressor of Cytokine Signaling 3 (SOCS3), Bcl-2 and Bcl-xL expression, and cytokine production was studied. In addition, the effects of globular and high-molecular-weight (HMW) APN on LPL-T cytokine production and apoptosis were studied. RESULTS: Higher levels of several chemokines, cytokines, and growth factors were present in AT near active than near inactive disease. A significantly higher amount of inflammatory infiltrate was present in AT near active CD than near ulcerative colitis, controls, and near the inactive area of CD. There were no changes in the ratios of APN molecular weight in control and IBD adipocyte products. Leptin and APN inhibited anti-CD3-stimulated-LPL-T apoptosis and potentiated STAT3 phosphorylation, Bcl-2, and Bcl-xL expression in IBD and control mucosa. However, SOCS3 expression was suppressed only in IBD. Both globular and HMW APN have similar effects on LPL-T cytokine production and apoptosis. Leptin and APN enhanced interleukin (IL)-10 production by anti-CD3-stimulated LPL-T in IBD only. APN, but not leptin, increased anti-CD3-induced IL-6 levels in LPL-T only in IBD patients. IL-10 exerts its anti-inflammatory

  13. 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

  14. 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.

  15. 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. PMID:26303886

  16. Noninvasive Testing for Mucosal Inflammation in Inflammatory Bowel Disease.

    PubMed

    Iborra, Marisa; Beltrán, Belén; Nos, Pilar

    2016-10-01

    Biomarkers have gained increasing attention for the diagnosis and follow-up of inflammatory bowel disease (IBD). Endoscopy remains the gold standard for assessing disease activity. Biomarkers are rapid, inexpensive, and noninvasive, and can be used in different stages of the disease with high sensitivity and specificity. Calprotectin and tests for C-reactive protein are used to assess the disease activity, predict relapse, and monitor treatment response. New noninvasive tests are being studied. This review discusses current evidence for these surrogate markers, their potential clinical applications, and limitations in disease management. We highlight recent advances in IBD biomarkers and future uses. PMID:27633593

  17. Noninvasive Testing for Mucosal Inflammation in Inflammatory Bowel Disease.

    PubMed

    Iborra, Marisa; Beltrán, Belén; Nos, Pilar

    2016-10-01

    Biomarkers have gained increasing attention for the diagnosis and follow-up of inflammatory bowel disease (IBD). Endoscopy remains the gold standard for assessing disease activity. Biomarkers are rapid, inexpensive, and noninvasive, and can be used in different stages of the disease with high sensitivity and specificity. Calprotectin and tests for C-reactive protein are used to assess the disease activity, predict relapse, and monitor treatment response. New noninvasive tests are being studied. This review discusses current evidence for these surrogate markers, their potential clinical applications, and limitations in disease management. We highlight recent advances in IBD biomarkers and future uses.

  18. So depression is an inflammatory disease, but where does the inflammation come from?

    PubMed Central

    2013-01-01

    Background We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to neuroprogression in the disorder. The obvious question this poses is ‘what is the source of this chronic low-grade inflammation?’ Discussion This review explores the role of inflammation and oxidative and nitrosative stress as possible mediators of known environmental risk factors in depression, and discusses potential implications of these findings. A range of factors appear to increase the risk for the development of depression, and seem to be associated with systemic inflammation; these include psychosocial stressors, poor diet, physical inactivity, obesity, smoking, altered gut permeability, atopy, dental cares, sleep and vitamin D deficiency. Summary The identification of known sources of inflammation provides support for inflammation as a mediating pathway to both risk and neuroprogression in depression. Critically, most of these factors are plastic, and potentially amenable to therapeutic and preventative interventions. Most, but not all, of the above mentioned sources of inflammation may play a role in other psychiatric disorders, such as bipolar disorder, schizophrenia, autism and post-traumatic stress disorder. PMID:24228900

  19. Inflammation and Inflammatory Cells in Myocardial Infarction and Reperfusion Injury: A Double-Edged Sword.

    PubMed

    Liu, Jiaqi; Wang, Haijuan; Li, Jun

    2016-01-01

    Myocardial infarction (MI) is the most common cause of cardiac injury, and subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Therefore, inflammation and inflammatory cell infiltration are the hallmarks of MI and reperfusion injury. Ischemic cardiac injury activates the innate immune response via toll-like receptors and upregulates chemokine and cytokine expressions in the infarcted heart. The recruitment of inflammatory cells is a dynamic and superbly orchestrated process. Sequential infiltration of the injured myocardium with neutrophils, monocytes and their descendant macrophages, dendritic cells, and lymphocytes contributes to the initiation and resolution of inflammation, infarct healing, angiogenesis, and ventricular remodeling. Both detrimental effects and a beneficial role in the pathophysiology of MI and reperfusion injury may be attributed to the subset heterogeneity and functional diversity of these inflammatory cells. PMID:27279755

  20. Inflammation and Inflammatory Cells in Myocardial Infarction and Reperfusion Injury: A Double-Edged Sword

    PubMed Central

    Liu, Jiaqi; Wang, Haijuan; Li, Jun

    2016-01-01

    Myocardial infarction (MI) is the most common cause of cardiac injury, and subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Therefore, inflammation and inflammatory cell infiltration are the hallmarks of MI and reperfusion injury. Ischemic cardiac injury activates the innate immune response via toll-like receptors and upregulates chemokine and cytokine expressions in the infarcted heart. The recruitment of inflammatory cells is a dynamic and superbly orchestrated process. Sequential infiltration of the injured myocardium with neutrophils, monocytes and their descendant macrophages, dendritic cells, and lymphocytes contributes to the initiation and resolution of inflammation, infarct healing, angiogenesis, and ventricular remodeling. Both detrimental effects and a beneficial role in the pathophysiology of MI and reperfusion injury may be attributed to the subset heterogeneity and functional diversity of these inflammatory cells. PMID:27279755

  1. 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

  2. Administration of Reconstituted Polyphenol Oil Bodies Efficiently Suppresses Dendritic Cell Inflammatory Pathways and Acute Intestinal Inflammation

    PubMed Central

    Cavalcanti, Elisabetta; Vadrucci, Elisa; Delvecchio, Francesca Romana; Addabbo, Francesco; Bettini, Simona; Liou, Rachel; Monsurrò, Vladia; Huang, Alex Yee-Chen; Pizarro, Theresa Torres

    2014-01-01

    Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation. PMID:24558444

  3. Interleukin-15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab

    PubMed Central

    Perrier, Clémentine; Arijs, Ingrid; Staelens, Dominiek; Breynaert, Christine; Cleynen, Isabelle; Covens, Kris; Ferrante, Marc; Assche, Gert; Vermeire, Séverine; Hertogh, Gert; Schuit, Frans; Rutgeerts, Paul; Ceuppens, Jan L

    2013-01-01

    Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL-15Rα, IL-15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription-PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL-15Rα were measured in sera of patients by ELISA and IL-15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL-15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non-responder patients. The concentration of sIL-15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non-responders either before or after IFX. CD patients have levels of sIL-15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL-15Rα+ cells closely resemble activated memory B cells with a pre-plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL-15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX. PMID:23039249

  4. 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.

  5. 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. PMID:26854026

  6. 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.

  7. 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 Central

    2009-01-01

    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 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 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 arise from inflammation and the inflammatory response. We are proposing

  8. 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

  9. Sleep and Inflammatory Bowel Disease: Exploring the Relationship Between Sleep Disturbances and Inflammation

    PubMed Central

    Kinnucan, Jami A.; Rubin, David T.

    2013-01-01

    Sleep disturbances are associated with a greater risk of serious adverse health events, economic consequences, and, most importantly, increased all-cause mortality. Several studies support the associations among sleep, immune function, and inflammation. The relationship between sleep disturbances and inflammatory conditions is complex and not completely understood. Sleep deprivation can lead to increased levels of inflammatory cytokines, including interleukin (IL)-1β IL-6, tumor necrosis factor-α and C-reactive protein, which can lead to further activation of the inflammatory cascade. The relevance of sleep in inflammatory bowel disease (IBD), a chronic immune-mediated inflammatory disease of the gastrointestinal tract, has recently received more attention. Several studies have shown that patients with both inactive and active IBD have self-reported sleep disturbances. Here, we present a concise review of sleep and its association with the immune system and the process of inflammation. We discuss the studies that have evaluated sleep in patients with IBD as well as possible treatment options for those patients with sleep disturbances. An algorithm for evaluating sleep disturbances in the IBD population is also proposed. Further research is still needed to better characterize sleep disturbances in the IBD population as well as to assess the effects of various therapeutic interventions to improve sleep quality. It is possible that the diagnosis and treatment of sleep disturbances in this population may provide an opportunity to alter disease outcomes. PMID:24764789

  10. 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.

  11. Lymphatic dysregulation in intestinal inflammation: new insights into inflammatory bowel disease pathomechanisms.

    PubMed

    Becker, F; Yi, P; Al-Kofahi, M; Ganta, V C; Morris, J; Alexander, J S

    2014-03-01

    Alterations in the intestinal lymphatic network are well-established features of human and experimental inflammatory bowel disease (IBD). Such lymphangiogenic expansion might enhance classic intestinal lymphatic transport, eliminating excess accumulations of fluid, inflammatory cells and mediators, and could therefore be interpreted as an 'adaptive' response to acute and chronic inflammatory processes. However, whether these new lymphatic vessels are functional, unregulated or immature (and what factors may promote 'maturation' of these vessels) is currently an area under intense investigation. It is still controversial whether impaired lymphatic function in IBD is a direct consequence of the intestinal inflammation, or a preceding lymphangitis-like event. Current research has uncovered novel regulatory factors as well as new roles for familiar signaling pathways, which appear to be linked to inflammation-induced lymphatic alterations. The current review summarizes mechanisms amplifying lymphatic dysregulation and remodeling in intestinal inflammation at the organ, cell and molecular levels and discusses the influence of lymphangiogenesis and intestinal lymphatic transport function as they relate to IBD pathophysiology.

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

    PubMed

    Khawar, Muhammad Babar; Abbasi, Muddasir Hassan; Sheikh, Nadeem

    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. 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

  14. 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.

  15. 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

  16. CD38 is expressed on inflammatory cells of the intestine and promotes intestinal inflammation.

    PubMed

    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.

  17. Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

    PubMed

    Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

    2014-11-01

    The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential.

  18. Mu opioid receptor expression is increased in inflammatory bowel diseases: implications for homeostatic intestinal inflammation

    PubMed Central

    Philippe, D; Chakass, D; Thuru, X; Zerbib, P; Tsicopoulos, A; Geboes, K; Bulois, P; Breisse, M; Vorng, H; Gay, J; Colombel, J‐F; Desreumaux, P; Chamaillard, M

    2006-01-01

    Background and aims Recent studies with μ opioid receptor (MOR) deficient mice support a physiological anti‐inflammatory effect of MOR at the colon interface. To better understand the potential pharmacological effect of certain opiates in inflammatory bowel diseases (IBD), we (1) evaluated the regulation in vivo and in vitro of human MOR expression by inflammation; and (2) tested the potential anti‐inflammatory function of a specific opiate (DALDA) in inflamed and resting human mucosa. Patients and methods Expression of MOR mRNA and protein was evaluated in healthy and inflamed small bowel and colonic tissues, isolated peripheral blood mononuclear cells and purified monocytes, and CD4+ and CD8+ T cells from healthy donors and IBD patients. The effect of cytokines and nuclear factor κB (NFκB) activation on MOR expression in lymphocyte T and monocytic human cell lines was assessed. Finally, DALDA induced anti‐inflammatory effect was investigated in mucosal explants from controls and IBD patients. Results MOR was expressed in ileal and colonic enteric neurones as well as in immunocytes such as myeloid cells and CD4+ and CD8+ T cells. Overexpressed in active IBD mucosa, MOR was significantly enhanced by cytokines and repressed by NFκB inhibitor in myeloid and lymphocytic cell lines. Furthermore, ex vivo DALDA treatment dampened tumour necrosis factor α mRNA expression in the colon of active IBD patients. Conclusions Given the increased expression of MOR and the ex vivo beneficial effect of DALDA in active IBD, natural and/or synthetic opioid agonists could help to prevent overt pathological intestinal inflammation. PMID:16299031

  19. 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. PMID:21443487

  20. 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).

  1. 4-methoxycarbonyl curcumin: a unique inhibitor of both inflammatory mediators and periodontal inflammation.

    PubMed

    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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. Macrophage-assisted inflammation and pharmacological regulation of the cholinergic anti-inflammatory pathway.

    PubMed

    Pohanka, M; Snopkova, S; Havlickova, K; Bostik, P; Sinkorova, Z; Fusek, J; Kuca, K; Pikula, Jiri

    2011-01-01

    Macrophages play an important role in the immune system. They also participate in multiple processes including angiogenesis and triggering of inflammation. The present study summarizes pieces of knowledge on the importance of macrophages in disease, especially the inflammation. Special attention is paid to the cholinergic anti-inflammatory pathway (CAP) associated with the nicotinic acetylcholine receptor (nAChR) and the parasympathetic nervous system. The current pharmacological effectiveness in suppressing the inflammation in general and the septic shock in particular, is limited. CAP was discovered recently and it seems to be a suitable target for the development of new drugs. Moreover, available drugs binding to either nAChR or acetylcholinesterase (AChE) are candidates for either an inhibition or enhancement of CAP. Though the current scientific databases do not include all necessary data on the association of CAP with body functions and the research is quite intensive, the objective of the present review is to introduce the current trends and to critically evaluate CAP and macrophage-associated pathways.

  7. Neuronal phagocytosis by inflammatory macrophages in ALS spinal cord: inhibition of inflammation by resolvin D1

    PubMed Central

    Liu, Guanghao; Fiala, Milan; Mizwicki, Mathew T; Sayre, James; Magpantay, Larry; Siani, Avi; Mahanian, Michelle; Chattopadhyay, Madhuri; Cava, Antonio La; Wiedau-Pazos, Martina

    2012-01-01

    Although the cause of neuronal degeneration in amyotrophic lateral sclerosis (ALS) remains hypothetical, there is evidence of spinal cord infiltration by macrophages and T cells. In post-mortem ALS spinal cords, 19.8 ± 4.8 % motor neurons, including caspase-negative and caspase-positive neurons, were ingested by IL-6- and TNF-α-positive macrophages. In ALS macrophages, in vitro aggregated superoxide dismutase-1 (SOD-1) stimulated in ALS macrophages expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α, through activation of cyclooxygenase-2 (COX-2) and caspase-1. The lipid mediator resolvin D1 (RvD1) inhibited IL-6 and TNF-α production in ALS macrophages with 1,100 times greater potency than its parent molecule docosahexaenoic acid. ALS peripheral blood mononuclear cells (PBMCs) showed increased transcription of inflammatory cytokines and chemokines at baseline and after stimulation by aggregated wild-type SOD-1, and these cytokines were down regulated by RvD1. Thus the neurons are impacted by macrophages expressing inflammatory cytokines. RvD1 strongly inhibits in macrophages and PBMCs cytokine transcription but does not inhibit their production in PBMCs. Resolvins offer a new approach to ALS inflammation suppressing. PMID:22787561

  8. A Functional Variant of Elafin With Improved Anti-inflammatory Activity for Pulmonary Inflammation

    PubMed Central

    Small, Donna M; Zani, Marie-Louise; Quinn, Derek J; Dallet-Choisy, Sandrine; Glasgow, Arlene MA; O'Kane, Cecilia; McAuley, Danny F; McNally, Paul; Weldon, Sinéad; Moreau, Thierry; Taggart, Clifford C

    2015-01-01

    Elafin is a serine protease inhibitor produced by epithelial and immune cells with anti-inflammatory properties. Research has shown that dysregulated protease activity may elicit proteolytic cleavage of elafin, thereby impairing the innate immune function of the protein. The aim of this study was to generate variants of elafin (GG- and QQ-elafin) that exhibit increased protease resistance while retaining the biological properties of wild-type (WT) elafin. Similar to WT-elafin, GG- and QQ-elafin variants retained antiprotease activity and susceptibility to transglutaminase-mediated fibronectin cross-linking. However, in contrast to WT-elafin, GG- and QQ-elafin displayed significantly enhanced resistance to degradation when incubated with bronchoalveolar lavage fluid from patients with cystic fibrosis. Intriguingly, both variants, particularly GG-elafin, demonstrated improved lipopolysaccharide (LPS) neutralization properties in vitro. In addition, GG-elafin showed improved anti-inflammatory activity in a mouse model of LPS-induced acute lung inflammation. Inflammatory cell infiltration into the lung was reduced in lungs of mice treated with GG-elafin, predominantly neutrophilic infiltration. A reduction in MCP-1 levels in GG-elafin treated mice compared to the LPS alone treatment group was also demonstrated. GG-elafin showed increased functionality when compared to WT-elafin and may be of future therapeutic relevance in the treatment of lung diseases characterized by a protease burden. PMID:25189740

  9. Current concepts in chronic inflammatory diseases: Interactions between microbes, cellular metabolism, and inflammation.

    PubMed

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T; Binder, Elisabeth B; Bisgaard, Hans; Chatila, Talal A; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Müller-Ladner, Ulf; Neurath, Markus F; Preissner, Klaus T; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald

    2016-07-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies. PMID:27373325

  10. 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

  11. 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

  12. 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.

  13. 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. PMID:27263829

  14. 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.

  15. Persistent infiltration and pro-inflammatory differentiation of monocytes cause unresolved inflammation in brain arteriovenous malformation.

    PubMed

    Zhang, Rui; Han, Zhenying; Degos, Vincent; Shen, Fanxia; Choi, Eun-Jung; Sun, Zhengda; Kang, Shuai; Wong, Michael; Zhu, Wan; Zhan, Lei; Arthur, Helen M; Oh, S Paul; Faughnan, Marie E; Su, Hua

    2016-10-01

    An abnormally high number of macrophages are present in human brain arteriovenous malformations (bAVM) with or without evidence of prior hemorrhage, causing unresolved inflammation that may enhance abnormal vascular remodeling and exacerbate the bAVM phenotype. The reasons for macrophage accumulation at the bAVM sites are not known. We tested the hypothesis that persistent infiltration and pro-inflammatory differentiation of monocytes in angiogenic tissues increase the macrophage burden in bAVM using two mouse models and human monocytes. Mouse bAVM was induced through deletion of AVM causative genes, Endoglin (Eng) globally or Alk1 focally, plus brain focal angiogenic stimulation. An endothelial cell and vascular smooth muscle cell co-culture system was used to analyze monocyte differentiation in the angiogenic niche. After angiogenic stimulation, the Eng-deleted mice had fewer CD68(+) cells at 2 weeks (P = 0.02), similar numbers at 4 weeks (P = 0.97), and more at 8 weeks (P = 0.01) in the brain angiogenic region compared with wild-type (WT) mice. Alk1-deficient mice also had a trend toward more macrophages/microglia 8 weeks (P = 0.064) after angiogenic stimulation and more RFP(+) bone marrow-derived macrophages than WT mice (P = 0.01). More CD34(+) cells isolated from peripheral blood of patients with ENG or ALK1 gene mutation differentiated into macrophages than those from healthy controls (P < 0.001). These data indicate that persistent infiltration and pro-inflammatory differentiation of monocytes might contribute to macrophage accumulation in bAVM. Blocking macrophage homing to bAVM lesions should be tested as a strategy to reduce the severity of bAVM. PMID:27325285

  16. 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

  17. Interactions between inflammation and lipid metabolism: relevance for efficacy of anti-inflammatory drugs in the treatment of atherosclerosis.

    PubMed

    van Diepen, Janna A; Berbée, Jimmy F P; Havekes, Louis M; Rensen, Patrick C N

    2013-06-01

    Dyslipidemia and inflammation are well known causal risk factors the development of atherosclerosis. The interplay between lipid metabolism and inflammation at multiple levels in metabolic active tissues may exacerbate the development of atherosclerosis, and will be discussed in this review. Cholesterol, fatty acids and modified lipids can directly activate inflammatory pathways. In addition, circulating (modified) lipoproteins modulate the activity of leukocytes. Vice versa, proinflammatory signaling (i.e. cytokines) in pre-clinical models directly affects lipid metabolism. Whereas the main lipid-lowering drugs all have potent anti-inflammatory actions, the lipid-modulating actions of anti-inflammatory agents appear to be less straightforward. The latter have mainly been evaluated in pre-clinical models and in patients with chronic inflammatory diseases, which will be discussed. The clinical trials that are currently conducted to evaluate the efficacy of anti-inflammatory agents in the treatment of cardiovascular diseases may additionally reveal potential (beneficial) effects of these therapeutics on lipid metabolism in the general population at risk for CVD.

  18. 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

  19. Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks.

    PubMed

    Beiter, Thomas; Hoene, Miriam; Prenzler, Frauke; Mooren, Frank C; Steinacker, Jürgen M; Weigert, Cora; Nieß, Andreas M; Munz, Barbara

    2015-01-01

    The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Hyperbaric oxygen treatment decreases inflammation and mechanical hypersensitivity in an animal model of inflammatory pain.

    PubMed

    Wilson, Hilary D; Wilson, Judy R; Fuchs, Perry N

    2006-07-01

    Hyperbaric oxygen therapy has been used to treat a variety of ailments from carbon monoxide poisoning to fibromyalgia. The purpose of this experiment was to explore the effect of hyperbaric oxygen treatment on carrageenan-induced inflammation and pain in rats. Hyperbaric oxygen treatment significantly decreased inflammation and pain following carrageenan injection. Clinically hyperbaric oxygen may be used in situations where NSAIDS are contraindicated or in persistent cases of inflammation.

  5. Role of vascular inflammation in coronary artery disease: potential of anti-inflammatory drugs in the prevention of atherothrombosis. Inflammation and anti-inflammatory drugs in coronary artery disease.

    PubMed

    Moreira, Daniel Medeiros; da Silva, Roberto Leo; Vieira, Jefferson Luís; Fattah, Tammuz; Lueneberg, Maria Emilia; Gottschall, Carlos Antonio Mascia

    2015-02-01

    Coronary artery disease (CAD) and acute myocardial infarction (AMI) are inflammatory pathologies, involving interleukins (ILs), such as IL-1β, IL-6 and tumor necrosis factor (TNF)-α, and acute phase proteins production, such as for C reactive protein (CRP). The process begins with retention of low-density lipoprotein (LDL) and its oxidation inside the intima, with the formation of the "foam cells." Toll-like receptors and inflamassomes participate in atherosclerosis formation, as well as in the activation of the complement system. In addition to innate immunity, adaptive immunity is also associated with atherosclerosis through antigen-presenting cells, T and B lymphocytes. AMI also increases the expression of some ILs and promotes macrophage and lymphocyte accumulation. Reperfusion increases the expression of anti-inflammatory ILs (such as IL-10) and generates oxygen free radicals. Although CAD and AMI are inflammatory disorders, the only drugs with anti-inflammatory effect so far widely used in ischemic heart disease are aspirin and statins. Some immunomodulatory or immunosuppressive promising therapies, such as cyclosporine and colchicine, may have benefits in CAD. Methotrexate also has potential cardioprotective anti-inflammatory effects, through increased adenosine levels. The TETHYS trial (The Effects of mETHotrexate Therapy on ST Segment Elevation MYocardial InfarctionS trial) will evaluate low-dose methotrexate in ST elevation AMI. The CIRT (Cardiovascular Inflammation Reduction Trial), in turn, will evaluate low-dose methotrexate in patients with a high prevalence of subclinical vascular inflammation. The CANTOS (The Canakinumab Antiinflammatory Thrombosis Outcomes Study) will evaluate canakinumab in patients with CAD and persistently elevated CRP. The blockage of other potential targets, such as the IL-6 receptor, CC2 chemokine receptor and CD20, could bring benefits in CAD.

  6. 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.

  7. [Inflammatory diseases of the gall bladder and biliary system. I. Imaging--cholelithasis--inflammation of the gall bladder].

    PubMed

    Helmberger, H; Kammer, B

    2005-05-01

    Cholelithiasis is the most common affliction of the gallbladder and biliary tract. Including its complications, gallstone disease represents the basis for cholecystitis and cholangitis in the majority of cases. Inflammatory diseases of the biliary system are divided into acute and chronic forms originating from the gallbladder as well as from the biliary tract. Although acute calculous cholecystitis is the most common form, gangrenous, and emphysematous inflammation of the gallbladder as well as gallbladder empyema are included in this group of diseases. In the chronic forms, calculous and acalculous inflammation is also differentiated. Recent developments in cross-sectional imaging in sonography, computed tomography, and magnetic resonance imaging offer numerous tools for depicting the biliary system with high diagnostic accuracy. Invasive imaging modalities of the biliary system are mainly used for therapeutic aspects. PMID:15875153

  8. Early Murine Cytomegalovirus (MCMV) Infection Induces Liver Natural Killer (NK) Cell Inflammation and Protection Through Macrophage Inflammatory Protein 1α (MIP-1α)–dependent Pathways

    PubMed Central

    Salazar-Mather, Thais P.; Orange, Jordan S.; Biron, Christine A.

    1998-01-01

    Natural killer (NK) cells mediate defense against early murine cytomegalovirus (MCMV) infections in liver. The chemokine, macrophage inflammatory protein 1α (MIP-1α), can promote inflammatory responses. Our studies evaluated contributions of NK cells to early MCMV-induced liver inflammation and MIP-1α requirements for inflammation and delivery of antiviral defenses. NK cells were shown to be responsible for focal inflammation, and to be induced to migrate at high levels, in MCMV-infected livers. MIP-1α gene expression was elevated at coinciding times, and mice deficient in MIP-1α function were dramatically inhibited in both inflammatory and protective liver responses. The results precisely define MIP-1α–dependent steps required to achieve NK cell inflammation during, and mechanisms promoting defense against, viral infections in tissues. PMID:9419206

  9. 1,25(OH)2D3 Deficiency Induces Colon Inflammation via Secretion of Senescence-Associated Inflammatory Cytokines

    PubMed Central

    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. PMID:26790152

  10. 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…

  11. Anti-Inflammatory and Antinociceptive Effects of Salbutamol on Acute and Chronic Models of Inflammation in Rats: Involvement of an Antioxidant Mechanism

    PubMed Central

    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. PMID:22665951

  12. 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.

  13. Anti-inflammatory and antioxidant effects of Jeevaneeya Rasayana: an ayurvedic polyherbal formulation on acute and chronic models of inflammation.

    PubMed

    Shyni, G L; Ratheesh, M; Sindhu, G; Helen, A

    2010-12-01

    The present study was aimed to establish the efficacy of Jeevaneeya Rasayana (JR), an ayurvedic polyherbal formulation, in adjuvant-induced arthritic (AIA) rat model with reference to mediators of inflammation. The methanolic (MJR), ethanolic (EJR), and water extracts (WJR) of JR were prepared and their anti-inflammatory activity in carrageenan-induced acute model was evaluated. MJR at a dose of 25 mg/kg showed significantly higher anti-inflammatory effect than EJR, WJR, and standard drug diclofenac. MJR also significantly decreased the paw edema in AIA rats. Activities of cyclooxygenase, 5-lipoxygenase, and myeloperoxidase were decreased significantly on treatment with MJR. Supplementation with MJR increases the activities of antioxidant enzymes and the level of glutathione content. The increment in the concentration of C-reactive protein, thiobarbituric acid reactive substance, and ceruloplasmin observed in arthritic rats were found to be significantly restored in MJR treated rats. Thus, the results demonstrated the potential beneficiary effect of methanolic extract of Jeevaneeya Rasayana on acute and chronic models of inflammation.

  14. 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.

  15. Therapies aimed at the gut microbiota and inflammation: antibiotics, prebiotics, probiotics, synbiotics, anti-inflammatory therapies.

    PubMed

    Quigley, Eamonn M M

    2011-03-01

    Several recent observations have raised the possibility that disturbances in the gut microbiota and/or a low-grade inflammatory state may contribute to symptomatology and the etiology of irritable bowel syndrome (IBS). Consequent on these hypotheses, several therapeutic categories have found their way into the armamentarium of those who care for IBS sufferers. These agents include probiotics, prebiotics, antibiotics, and anti-inflammatory agents.

  16. Expression and Sequence Variants of Inflammatory Genes; Effects on Plasma Inflammation Biomarkers Following a 6-Week Supplementation with Fish Oil

    PubMed Central

    Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2016-01-01

    (1) Background: A growing body of literature suggest that polymorphisms (SNPs) from inflammation-related genes could possibly play a role in cytokine production and then interact with dietary n-3 fatty acids (FAs) to modulate inflammation. The aim of the present study was to test whether gene expression of selected inflammatory genes was altered following an n-3 PUFA supplementation and to test for gene–diet interactions modulating plasma inflammatory biomarker levels. (2) Methods: 191 subjects completed a 6-week n-3 FA supplementation with 5 g/day of fish oil. Gene expression of TNF-α and IL6 was assessed in peripheral blood mononuclear cells (PBMCs) using the TaqMan technology. Genotyping of 20 SNPs from the TNF-LTA gene cluster, IL1β, IL6 and CRP genes was performed. (3) Results: There was no significant reduction of plasma IL-6, TNF-α and C-reactive protein (CRP) levels after the 6-week fish oil supplementation. TNF-α and IL6 were slightly overexpressed in PBMCs after the supplementation (fold changes of 1.05 ± 0.38 and 1.18 ± 0.49, respectively (n = 191)), but relative quantification (RQ) within the −0.5 to 2.0 fold are considered as nonbiologically significant. In a MIXED model for repeated measures adjusted for the effects of age, sex and BMI, gene by supplementation interaction effects were observed for rs1143627, rs16944, rs1800797, and rs2069840 on IL6 levels, for rs2229094 on TNF-α levels and for rs1800629 on CRP levels (p < 0.05 for all). (4) Conclusions: This study shows that a 6-week n-3 FA supplementation with 5 g/day of fish oil did not alter gene expression levels of TNF-α and IL6 in PBMCs and did not have an impact on inflammatory biomarker levels. However, gene–diet interactions were observed between SNPs within inflammation-related genes modulating plasma inflammatory biomarker levels. PMID:26999109

  17. Zingerone suppresses liver inflammation induced by antibiotic mediated endotoxemia through down regulating hepatic mRNA expression of inflammatory markers in Pseudomonas aeruginosa peritonitis mouse model.

    PubMed

    Kumar, Lokender; Chhibber, Sanjay; Harjai, Kusum

    2014-01-01

    Antibiotic-induced endotoxin release is associated with high mortality rate even when appropriate antibiotics are used for the treatment of severe infections in intensive care units. Since liver is involved in systemic clearance and detoxification of endotoxin hence it becomes a primary target organ for endotoxin mediated inflammation. Currently available anti-inflammatory drugs give rise to serious side effects. Hence, there is an urgent need for safe and effective anti-inflammatory therapy. It is likely that anti-inflammatory phytochemicals and neutraceutical agents may have the potential to reduce the endotoxin mediated inflammation and complications associated with endotoxin release. Keeping this in mind, the present study was planned to evaluate the hepatoprotective potential of zingerone (active compound of zingiber officinale) against liver inflammation induced by antibiotic mediated endotoxemia. The selected antibiotics capable of releasing high content of endotoxin were employed for their in vivo efficacy in P.aeruginosa peritonitis model. Released endotoxin induced inflammation and zingerone as co-anti-inflammatory therapy significantly reduced inflammatory response. Improved liver histology and reduced inflammatory markers MDA, RNI, MPO, tissue damage markers (AST, ALT, ALP) and inflammatory cytokines (MIP-2, IL-6 and TNF-α) were indicative of therapeutic potential of zingerone. The mechanism of action of zingerone may be related to significant inhibition of the mRNA expression of inflammatory markers (TLR4, RelA, NF-kB2, TNF- α, iNOS, COX-2) indicating that zingerone interferes with cell signalling pathway and suppresses hyper expression of cell signaling molecules of inflammatory pathway. Zingerone therapy significantly protected liver from endotoxin induced inflammatory damage by down regulating biochemical as well as molecular markers of inflammation. In conclusion, this study provides evidence that zingerone is a potent anti-inflammatory

  18. IL‐10 differentially controls the infiltration of inflammatory macrophages and antigen‐presenting cells during inflammation

    PubMed Central

    Liao, Chia‐Te; Rosas, Marcela; Davies, Luke C.; Giles, Peter J.; Tyrrell, Victoria J.; O'Donnell, Valerie B.; Topley, Nicholas; Humphreys, Ian R.; Fraser, Donald J.; Jones, Simon A.

    2016-01-01

    The inflammatory activation and recruitment of defined myeloid populations is essential for controlling the bridge between innate and adaptive immunity and shaping the immune response to microbial challenge. However, these cells exhibit significant functional heterogeneity and the inflammatory signals that differentially influence their effector characteristics are poorly characterized. In this study, we defined the phenotype of discrete subsets of effective antigen‐presenting cells (APCs) in the peritoneal cavity during peritonitis. When the functional properties of these cells were compared to inflammatory monocyte‐derived macrophages we noted differential responses to the immune‐modulatory cytokine IL‐10. In contrast to the suppressive actions of IL‐10 on inflammatory macrophages, the recruitment of APCs was relatively refractory and we found no evidence for selective inhibition of APC differentiation. This differential response of myeloid cell subsets to IL‐10 may thus have limited impact on development of potentially tissue‐damaging adaptive immune responses, while restricting the magnitude of the inflammatory response. These findings may have clinical relevance in the context of peritoneal dialysis patients, where recurrent infections are associated with immune‐mediated membrane dysfunction, treatment failure, and increased morbidity. PMID:27378515

  19. Anti-inflammatory effects of Houttuynia cordata supercritical extract in carrageenan-air pouch inflammation model.

    PubMed

    Kim, Dajeong; Park, Dongsun; Kyung, Jangbeen; Yang, Yun-Hui; Choi, Ehn-Kyoung; Lee, Yoon-Bok; Kim, Hyun-Kyu; Hwang, Bang Yeon; Kim, Yun-Bae

    2012-06-01

    Anti-inflammatory effects of Houttuynia cordata supercritical extract (HSE) were investigated in rat carrageenan-air pouch model. Oral administration of HSE (50-200 mg/kg) suppressed carrageenan-induced exudation and albumin leakage, as well as inflammatory cell infiltration at a high dose (200 mg/kg). Intraperitoneal injection of dexamethasone (2 mg/kg) only decreased exudation and cell infiltration, while indomethacin (2 mg/kg, i.p.) reduced exudate volume and albumin content without influence on the cell number. HSE lowered tumor-necrosis factor-α (TNF-α) and nitric oxide (NO), as well as prostaglandin E(2) (PGE(2)). Dexamethasone only reduced TNF-α and NO, while indomethacin decreased PGE(2). The results indicate that HSE exhibits anti-inflammatory effects by inhibiting both TNF-α-NO and cyclooxygenase-2-PGE(2) pathways. PMID:22787488

  20. 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

  1. 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.

  2. 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. PMID:27127234

  3. 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.

  4. 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.

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

    PubMed

    Kim, Ohn Soon; Lee, Chang Seok; Joe, Eun-hye; Jou, Ilo

    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.

  6. 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.

  7. 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

  8. Blockade of PLD2 Ameliorates Intestinal Mucosal Inflammation of Inflammatory Bowel Disease

    PubMed Central

    Zhou, Guangxi; Yu, Lin; Yang, Wenjing; Wu, Wei; Fang, Leilei

    2016-01-01

    Background. Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronically remittent and progressive inflammatory disorders. Phospholipase D2 (PLD2) is reported to be involved in the pathogenesis of several inflammatory diseases. However, the exact role of PLD2 in IBD is obscure. Methods. PLD2 expression was determined in peripheral blood cells and inflamed mucosa from patients with IBD by qRT-PCR. Colonic biopsies were also obtained from CD patients before and after infliximab (IFX) treatment to examine PLD2 expression. PLD2 selective inhibitor (CAY10594) was administrated daily by oral gavage in DSS-induced colitis mice. Bone marrow neutrophils from colitis mice were harvested to examine the migration using Transwell plate. Results. PLD2 was found to be significantly increased in peripheral blood cells and inflamed mucosa in patients with active IBD. Treatment with IFX could significantly decrease PLD2 expression in intestinal mucosa in patients with CD. Moreover, blockade of PLD2 with CAY10594 could markedly ameliorate DSS-induced colitis in mice and promote neutrophil migration. Conclusions. PLD2 plays a critical role in the pathogenesis of IBD. Blockade of PLD2 may serve as a new therapeutic approach for treatment of IBD. PMID:27721573

  9. 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.

  10. HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation

    PubMed Central

    2012-01-01

    Background The pathogenesis of allergic airway inflammation in asthmatic patients is complex and characterized by cellular infiltrates and activity of many cytokines and chemokines. Both the transcription factor hypoxia inducible factor-1 (HIF-1) and chemokine CCL2 have been shown to play pivotal roles in allergic airway inflammation. The interrelationship between these two factors is not known. We hypothesized that the expression of HIF-1 and CCL2 may be correlated and that the expression of CCL2 may be under the regulation of HIF-1. Several lines of evidence are presented to support this hypothesis. Methods The effects of treating wild-type OVA (ovalbumin)-sensitized/challenged mice with ethyl-3,4-dihydroxybenzoate (EDHB), which upregulate HIF, on CCL2 expression, were determined. Mice conditionally knocked out for HIF-1β was examined for their ability to mount an allergic inflammatory response and CCL2 expression in the lung after intratracheal exposure to ovalbumin. The association of HIF-1α and CCL2 levels was also measured in endobronchial biopsies and bronchial fluid of asthma patients after challenge. Results We show that both HIF-1α and CCL2 were upregulated during an OVA (ovalbumin)-induced allergic response in mice. The levels of HIF-1α and CCL2 were significantly increased following treatment with a pharmacological agent which upregulates HIF-1α, ethyl-3,4-dihydroxybenzoate (EDHB). In contrast, the expression levels of HIF-1α and CCL2 were decreased in the lungs of mice that have been conditionally knocked out for ARNT (HIF-1β) following sensitization with OVA when compared to levels in wild type mice. In asthma patients, the levels of HIF-1α and CCL2 increased after challenge with the allergen. Conclusions These data suggest that CCL2 expression is regulated, in part, by HIF-1 in the lung. These findings also demonstrate that both CCL2 and HIF-1 are implicated in the pathogenesis of allergic airway inflammation. PMID:22823210

  11. Derivation and validation of murine histologic alterations resembling asthma, with two proposed histologic grade parameters

    PubMed Central

    Wachtel, Mitchell S; Shome, Goutam; Sutherland, Mhairi; McGlone, John J

    2009-01-01

    Background The objective was to define murine histologic alterations resembling asthma in a BALB/c OVA model and to suggest grading criteria. Identified were six salient histologic findings in lungs with putative allergic inflammation: 1) bronchoarterial space inflammation; 2) peri-venular inflammation; 3) inflammation about amuscular blood vessels; 4) inter-alveolar space inflammation, not about capillaries; 5) pleural inflammation; and 6) eosinophils within the inflammatory aggregates. An initial study comprised six groups of twelve mice each: 1) stressed, control; 2) stressed, sensitized; 3) stressed, challenged; 4) not physically stressed, control; 5) not physically stressed, sensitized; 6) not physically stressed, challenged. A second study comprised four experimental groups of twenty mice each: 1) stressed, control; 2) stressed, challenged; 3) not physically stressed, control; 4) not physically stressed, challenged. A third study evaluated two grading criteria, 1) the proportion of non-tracheal respiratory passages with inflammatory aggregates and 2) mitoses in the largest two non-tracheal respiratory passages, in five groups of five mice each, evaluated at different times after the last exposure. Results The first study suggested the six histological findings might reliably indicate the presence of alterations resembling asthma: whereas 82.4% of mice with a complete response had detectable interleukin (IL)-5, only 3.8% of mice without one did; whereas 77.8% of mice with a complete response were challenged mice, only 6.7% of mice without complete responses were. The second study revealed that the six histological findings provided a definition that was 97.4% sensitive and 100% specific. The third study found that the odds of a bronchial passage's having inflammation declined 1) when mitoses were present (OR = 0.73, 0.60 - 0.90), and 2) with one day increased time (OR = 0.75, 0.65 - 0.86). Conclusion A definition of murine histologic alterations resembling

  12. 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.

  13. Bronchodilator and Anti-Inflammatory Action of Theophylline in a Model of Ovalbumin-Induced Allergic Inflammation.

    PubMed

    Urbanova, A; Kertys, M; Simekova, M; Mikolka, P; Kosutova, P; Mokra, D; Mokry, J

    2016-01-01

    Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5' monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-selective inhibitor of PDEs. Theophylline has been used for decades in the treatment of chronic inflammatory airway diseases. It has a narrow therapeutic window and belongs to the drugs whose plasma concentration should be monitored. Therefore, the main goal of this study was to evaluate the plasma theophylline concentration and to determine its relevance to pharmacological effects after single and longer term (7 days) administration of theophylline at different doses (5, 10, 20, and 50 mg/kg) in guinea pigs. Airway hyperresponsiveness was assessed by repeated exposure to ovalbumin. Theophylline reduced specific airway resistance in response to histamine nebulization, measured in a double chamber body plethysmograph. A decrease in tracheal smooth muscle contractility after cumulative doses of histamine and acetylcholine was confirmed in vitro. A greater efficacy of theophylline after seven days long treatment indicates the predominance of its anti-inflammatory activity, which may be involved in the bronchodilating action. PMID:27334733

  14. Bronchodilator and Anti-Inflammatory Action of Theophylline in a Model of Ovalbumin-Induced Allergic Inflammation.

    PubMed

    Urbanova, A; Kertys, M; Simekova, M; Mikolka, P; Kosutova, P; Mokra, D; Mokry, J

    2016-01-01

    Phosphodiesterases (PDEs) represent a super-family of 11 enzymes hydrolyzing cyclic nucleotides into inactive 5' monophosphates. Inhibition of PDEs leads to a variety of cellular effects, including airway smooth muscle relaxation, inhibition of cellular inflammation, and immune responses. In this study we focused on theophylline, a known non-selective inhibitor of PDEs. Theophylline has been used for decades in the treatment of chronic inflammatory airway diseases. It has a narrow therapeutic window and belongs to the drugs whose plasma concentration should be monitored. Therefore, the main goal of this study was to evaluate the plasma theophylline concentration and to determine its relevance to pharmacological effects after single and longer term (7 days) administration of theophylline at different doses (5, 10, 20, and 50 mg/kg) in guinea pigs. Airway hyperresponsiveness was assessed by repeated exposure to ovalbumin. Theophylline reduced specific airway resistance in response to histamine nebulization, measured in a double chamber body plethysmograph. A decrease in tracheal smooth muscle contractility after cumulative doses of histamine and acetylcholine was confirmed in vitro. A greater efficacy of theophylline after seven days long treatment indicates the predominance of its anti-inflammatory activity, which may be involved in the bronchodilating action.

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

    PubMed

    Liu, Jun-Shan; Wei, Xi-Duan; Lu, Zi-Bin; Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-04-19

    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

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

    PubMed

    Liu, Jun-Shan; Wei, Xi-Duan; Lu, Zi-Bin; Xie, Pei; Zhou, Hong-Ling; Chen, Yu-Yao; Ma, Jia-Mei; Yu, Lin-Zhong

    2016-04-19

    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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Glucocorticoids and inflammation: a double-headed sword in depression? How do neuroendocrine and inflammatory pathways interact during stress to contribute to the pathogenesis of depression?

    PubMed

    Horowitz, M A; Zunszain, P A; Anacker, C; Musaelyan, K; Pariante, C M

    2013-01-01

    Both glucocorticoids and inflammation have been implicated in the pathogenesis of depression. There is a large body of literature indicating that hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid receptor (GR) dysfunction are present in a significant proportion of depressed patients. There is also evidence of increased inflammatory processes in depressed populations, with higher levels of cytokines being a prominent finding - including raised levels of IL-6, and IL-1. These findings appear difficult to reconcile given the well-recognised property of glucocorticoids as prominent anti-inflammatory molecules. There are three potential solutions posed to this dilemma. Firstly, it has been argued that the glucocorticoid system and the inflammatory system exist in balance with one another and chronic stress can disrupt this balance in favour of inflammatory processes at the expense of glucocorticoid signalling. It has also been suggested that glucocorticoids have more complex actions than typically thought, and, in low levels can actually be pro-inflammatory, rather than universally anti-inflammatory. Lastly, it is possible that inflammation and glucocorticoid signalling may act on the same processes and structures without direct interaction to give rise to cumulative damage. Improved understanding of this interaction will allow further progress in determining targets for treatment.

  3. [Mycosis fungoides or inflammatory dermatitis: differential diagnosis between early lymphoma and inflammation in skin biopsies].

    PubMed

    Oschlies, I; Klapper, W

    2013-05-01

    Mycosis fungoides is a cutaneous T-cell lymphoma with protracted clinical course and progression in different stages with increasing aggressiveness. The clinical picture as well as the histopathology of mycosis fungoides within the early patch and plaque phase is difficult to delineate from some inflammatory skin diseases. Thus, the diagnosis of these early stages of the lymphoma is only possible when clinical, histopathological, and molecular features are integrated into the diagnosis, especially as none of the individual disease criteria is specific. Important clues towards the diagnosis of mycosis fungoides are cytologically abnormal epidermotropic CD4-positive T-cells causing only minor epidermal alterations, the formation of Pautrier-abscesses and basal alignment of the epidermotropic T-cells. The findings of an aberrant T-cell immunophenotype of the intraepidermal lymphoid component as well as the molecular proof of T-cell clonality are important further features. In the differential diagnosis between early stage mycosis fungoides and parapsoriasis, there remains nevertheless a diagnostic and maybe also a true biological grey zone. PMID:23549914

  4. Fecal lactoferrin, a marker of intestinal inflammation in children with inflammatory bowel disease.

    PubMed

    Borkowska, Anna; Liberek, Anna; Łuczak, Grażyna; Jankowska, Agnieszka; Plata-Nazar, Katarzyna; Korzon, Maria; Kamińska, Barbara

    2015-01-01

    The aim of this study was to analyze the usefulness of fecal lactoferrin in the diagnosis and monitoring of inflammatory bowel disease (IBD) in children. The study included 52 children with IBD (24 with Crohn's disease and 28 with ulcerative colitis) aged between 0.92 and 18 years, and 41 IBD-free controls of similar age. Fecal concentration of lactoferrin was determined with a quantitative immunoenzymatic test. Fecal concentration of lactoferrin in children with IBD was significantly higher than in the controls. The cut-off value of fecal lactoferrin concentration optimally distinguishing between the children with IBD and the controls was identified as 13 μg/g. The sensitivity and specificity of this cut-off value equaled 80.7% and 92.7%, respectively, and its positive and negative prognostic values were 96.8% and 63.3%, respectively. Patients diagnosed with moderate Crohn's disease had significantly higher fecal concentrations of lactoferrin than children with the mild or inactive disease. Similarly, children with moderate ulcerative colitis showed significantly higher fecal concentrations of lactoferrin than individuals with the mild condition. No significant relationship was found between the fecal concentration of lactoferrin and the severity of endoscopic lesions. Patients with IBD and a positive result of fecal occult blood test were characterized by significantly higher concentrations of lactoferrin than the individuals with IBD and a negative result of this test. In conclusion, fecal concentration of lactoferrin seems to be a useful parameter for diagnosis and monitoring of IBD in children.

  5. Ursolic acid prevents augmented peripheral inflammation and inflammatory hyperalgesia in high-fat diet-induced obese rats by restoring downregulated spinal PPARα.

    PubMed

    Zhang, Yanan; Song, Chengwei; Li, Haiou; Hou, Jingdong; Li, Dongliang

    2016-06-01

    Obesity is a risk factor for several pain syndromes and is associated with increased pain sensitivity. Evidence suggests that obesity causes the downregulation of peroxisome proliferator‑activated receptor (PPAR)α in the spinal cord, contributing to augmented peripheral edema and inflammatory hyperalgesia. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has been shown to upregulate PPARα in the peripheral tissues of obese animals. The present study hypothesized that UA prevents augmented peripheral inflammation and inflammatory hyperalgesia in obesity by restoring downregulated spinal PPARα. The present study demonstrated that Sprague‑Dawley rats fed a high‑fat diet (HFD) for 12 weeks developed obesity and metabolic disorder. Following carrageenan injection, the HFD rats exhibited increased thermal hyperalgesia and paw edema, compared with the rats fed a low‑fat diet. Molecular investigations revealed that the HFD rats exhibited decreased PPARα activity, and exaggerated expression of inflammatory mediators and nuclear factor‑kB activity in the spinal cord in response to carrageenan. Oral administration of UA ameliorated obesity and metabolic disorder, and prevented increased thermal hyperalgesia and paw edema in the HFD rats. Additionally, UA normalized PPARα activity and inhibited the exaggerated spinal cord inflammatory response to carrageenan. Although the knockdown of spinal PPARα with small interfering RNA following the administration of UA did not alter obesity or metabolic parameters, it eradicated the beneficial effects of UA on thermal hyperalgesia and paw edema, and reversed the spinal cord inflammatory response. These results suggested that the systemic administration of UA inhibited the exaggerated spinal cord inflammatory response to peripheral inflammatory stimulation in HFD‑induced obesity by restoring downregulated spinal PPARα, preventing peripheral inflammation and inflammatory hyperalgesia. UA may be a

  6. Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

    PubMed

    dos Santos, Solange Almeida; Alves, Ana Carolina Araruna; Leal-Junior, Ernesto Cesar Pinto; Albertini, Regiane; Vieira, Rodolfo de Paula; Ligeiro, Ana Paula; Junior, Jose Antonio Silva; de Carvalho, Paulo de Tarso Camillo

    2014-05-01

    Synovial membrane inflammation plays an important role in osteoarthritis (OA) pathophysiology. The synovial tissue of patients with initial OA is characterized by mononuclear cell infiltration and the production of pro-inflammatory cytokines and other mediators of joint injury. The study aims to evaluate the effect of low-level laser therapy (LLLT) at doses of 2 and 4 J on joint inflammation in rats induced by papain through histopathological analysis, differential counts of inflammatory cells; gene expression of IL-1β, IL-6, and IL-10; and TNF-α protein expression. Male Wistar rats (20) were randomly divided (5 animals each) into a negative control group, an inflammation injury positive control group, a 2-J LLLT group subjected to injury and treated with 2 J of LLLT, and a 4-J LLLT group subjected to injury and treated with 4 J of LLLT. The animals were subjected to joint inflammation (4 % papain solution) and treated with LLLT. On the day of euthanasia, articular lavage was collected and centrifuged. The supernatant was analyzed for TNF-α protein expression by ELISA and IL-1β, IL-6, and IL-10 mRNA by RT-PCR. The joint tissue was also examined histologically. ANOVA with Tukey's post hoc test was used for comparisons. All data were expressed as means ± S.D. (p < 0.05). Both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1β and IL-6. However, the 2-J treatment led to more reduction in TNF-α than the 4-J treatment. A single application of LLLT with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells.

  7. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism.

    PubMed

    Larrosa, Mar; González-Sarrías, Antonio; Yáñez-Gascón, María J; Selma, María V; Azorín-Ortuño, María; Toti, Simona; Tomás-Barberán, Francisco; Dolara, Piero; Espín, Juan Carlos

    2010-08-01

    Whether the beneficial effects of pomegranate are due to the ellagitannins or to their microbiota-derived urolithins is not known. Our objectives were to evaluate the effects of pomegranate intake and its main microbiota-derived metabolite urolithin-A (UROA) on colon inflammation and to assess whether UROA is the main anti-inflammatory compound. In addition, the effect of the inflammation on the phenolic metabolism was also explored. Male Fisher rats were fed with 250 mg kg(-1) day(-1) pomegranate extract (PE) or 15 mg kg(-1) day(-1) UROA for 25 days. Dextran sodium sulfate (5%) (DSS) was administered for the five last days and then rats were euthanized. DSS is a well-known model of inflammatory bowel disease. Colon tissue damage, microbiota changes, antioxidant status, prostaglandin E(2) (PGE(2)), nitric oxide production, inducible nitric oxide synthase (iNOS), prostaglandin E synthase (PTGES), gene expression (microarrays and RT-PCR) and polyphenol metabolism (LC-MS-MS) were evaluated. Both PE and UROA decreased inflammation markers (iNOS, cycloxygenase-2, PTGES and PGE(2) in colonic mucosa) and modulated favorably the gut microbiota. The G(1) to S cell cycle pathway was up-regulated in both groups. UROA group showed various down-regulated pathways, including that of the inflammatory response. PE, but not UROA, decreased oxidative stress in plasma and colon mucosa. Only UROA preserved colonic architecture. The normal formation of urolithins in PE-fed rats was prevented during inflammation. Our results suggest that UROA could be the most active anti-inflammatory compound derived from pomegranate ingestion in healthy subjects, whereas in colon inflammation, the effects could be due to the nonmetabolized ellagitannin-related fraction.

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

    PubMed Central

    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. PMID:26207636

  9. 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

  10. 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

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

    PubMed

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

    2016-04-26

    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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. Studies on anti-inflammatory activity of spice principles and dietary n-3 polyunsaturated fatty acids on carrageenan-induced inflammation in rats.

    PubMed

    Reddy, A C; Lokesh, B R

    1994-01-01

    The antioxidant spice principles curcumin and eugenol when given by gavage lowered the carrageenan-induced edema in the foot pads of rats. This lowering effect was dependent on the concentration, the time gap between the administration of spice principles and the induction of inflammation by carrageenan. Dietary lipids also influenced the extent of inflammation. Animals fed 10% cod liver oil [containing n-3 polyunsaturated fatty acids (PUFA)] for 10 weeks showed a significantly lower inflammation compared to that observed in animals fed diets supplemented with 10% groundnut oil (rich in n-6 PUFA) or 10% coconut oil (rich in medium-chain saturated fatty acids). Supplementation of diets with 1 weight% of curcumin did not affect the inflammatory responses of animals to carrageenan injection. However, supplementation of diets with 0.17 weight% eugenol further lowered inflammation by 16, 32 and 30% in animals fed coconut oil, groundnut oil and cod liver oil, respectively. Therefore, combinations of dietary lipids with spice principles like eugenol can help in lowering inflammation.

  18. Activation of the nuclear factor-κB pathway during postnatal lung inflammation preserves alveolarization by suppressing macrophage inflammatory protein-2.

    PubMed

    Hou, Yanli; Liu, Min; Husted, Cristiana; Chen, Chihhsin; Thiagarajan, Kavitha; Johns, Jennifer L; Rao, Shailaja P; Alvira, Cristina M

    2015-09-15

    A significant portion of lung development is completed postnatally during alveolarization, rendering the immature lung vulnerable to inflammatory stimuli that can disrupt lung structure and function. Although the NF-κB pathway has well-recognized pro-inflammatory functions, novel anti-inflammatory and developmental roles for NF-κB have recently been described. Thus, to determine how NF-κB modulates alveolarization during inflammation, we exposed postnatal day 6 mice to vehicle (PBS), systemic lipopolysaccharide (LPS), or the combination of LPS and the global NF-κB pathway inhibitor BAY 11-7082 (LPS + BAY). LPS impaired alveolarization, decreased lung cell proliferation, and reduced epithelial growth factor expression. BAY exaggerated these detrimental effects of LPS, further suppressing proliferation and disrupting pulmonary angiogenesis, an essential component of alveolarization. The more severe pathology induced by LPS + BAY was associated with marked increases in lung and plasma levels of macrophage inflammatory protein-2 (MIP-2). Experiments using primary neonatal pulmonary endothelial cells (PEC) demonstrated that MIP-2 directly impaired neonatal PEC migration in vitro; and neutralization of MIP-2 in vivo preserved lung cell proliferation and pulmonary angiogenesis and prevented the more severe alveolar disruption induced by the combined treatment of LPS + BAY. Taken together, these studies demonstrate a key anti-inflammatory function of the NF-κB pathway in the early alveolar lung that functions to mitigate the detrimental effects of inflammation on pulmonary angiogenesis and alveolarization. Furthermore, these data suggest that neutralization of MIP-2 may represent a novel therapeutic target that could be beneficial in preserving lung growth in premature infants exposed to inflammatory stress.

  19. 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.

  20. 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.

  1. 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. PMID:19931610

  2. 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. PMID:22588629

  3. Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway.

    PubMed

    Wu, Xiafei; Zhang, Feng; Xiong, Xin; Lu, Chunfeng; Lian, Naqi; Lu, Yin; Zheng, Shizhong

    2015-04-01

    Hepatic fibrosis is concomitant with liver inflammation, which has been highlighted as significant treatment of chronic liver disease. We previously demonstrated that tetramethylpyrazine (TMP), the effective component of Ligusticum chuanxiong Hort, can inhibit the activation of HSCs and consequential anti-hepatic fibrosis. In this study, our work demonstrated that TMP improved liver histological architecture, decreased hepatic enzyme levels and attenuated collagen deposition in the rat fibrotic liver. In addition, TMP significantly protected the liver from CCl4-caused injury and fibrogenesis by suppressing inflammation with reducing levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), NLRP3, nuclear factor-kappa B (NF-κB) and interleukin-1β (IL-1β). Experiments in vitro showed that TMP inhibited inflammatory cytokine expression in HSCs associated with disrupting platelet-derived growth factor-b receptor (PDGF-βR)/NLRP3/caspase1 pathway. These data collectively indicate that TMP can attenuate liver inflammation in liver fibrosis and possibly by targeting HSCs via PDGF-βR/NLRP3/caspase1 pathway. It provides novel mechanistic insights into TMP as a potential therapeutic remedy for hepatic fibrosis. PMID:25847612

  4. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage

    PubMed Central

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-01-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4 (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.—Sasso, O., Migliore, M., Habrant, D., Armirotti, A., Albani, C., Summa, M., Moreno-Sanz, G., Scarpelli, R., Piomelli, D. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage. PMID:25757568

  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. 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.

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

    PubMed Central

    Je, In-Gyu; Kim, Hui-Hun; Park, Pil-Hoon; Kwon, Taeg Kyu

    2015-01-01

    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. PMID:25349218

  9. 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…

  10. Anti-inflammatory effects of oleanolic acid on LPS-induced inflammation in vitro and in vivo.

    PubMed

    Lee, Wonhwa; Yang, Eun-Ju; Ku, Sae-Kwang; Song, Kyung-Sik; Bae, Jong-Sup

    2013-02-01

    Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects of OA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by LPS and the associated signaling pathways. We found that OA inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocyte migration in vivo. Further studies revealed that OA suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by LPS. Collectively, these results suggest that OA has anti-inflammatory effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapeutic agent for vascular inflammatory diseases.

  11. Multitarget fatty acid amide hydrolase/cyclooxygenase blockade suppresses intestinal inflammation and protects against nonsteroidal anti-inflammatory drug-dependent gastrointestinal damage.

    PubMed

    Sasso, Oscar; Migliore, Marco; Habrant, Damien; Armirotti, Andrea; Albani, Clara; Summa, Maria; Moreno-Sanz, Guillermo; Scarpelli, Rita; Piomelli, Daniele

    2015-06-01

    The ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to inhibit cyclooxygenase (Cox)-1 and Cox-2 underlies the therapeutic efficacy of these drugs, as well as their propensity to damage the gastrointestinal (GI) epithelium. This toxic action greatly limits the use of NSAIDs in inflammatory bowel disease (IBD) and other chronic pathologies. Fatty acid amide hydrolase (FAAH) degrades the endocannabinoid anandamide, which attenuates inflammation and promotes GI healing. Here, we describe the first class of systemically active agents that simultaneously inhibit FAAH, Cox-1, and Cox-2 with high potency and selectivity. The class prototype 4: (ARN2508) is potent at inhibiting FAAH, Cox-1, and Cox-2 (median inhibitory concentration: FAAH, 0.031 ± 0.002 µM; Cox-1, 0.012 ± 0.002 µM; and Cox-2, 0.43 ± 0.025 µM) but does not significantly interact with a panel of >100 off targets. After oral administration in mice, ARN2508 engages its intended targets and exerts profound therapeutic effects in models of intestinal inflammation. Unlike NSAIDs, ARN2508 causes no gastric damage and indeed protects the GI from NSAID-induced damage through a mechanism that requires FAAH inhibition. Multitarget FAAH/Cox blockade may provide a transformative approach to IBD and other pathologies in which FAAH and Cox are overactive.

  12. 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

  13. Effects of histidine and N-acetylcysteine on diclofenac-induced anti-inflammatory response in acute inflammation in rats.

    PubMed

    Farshid, Amir Abbas; Tamaddonfard, Esmaeal; Yahyaee, Fatere

    2010-11-01

    The intra-plantar injection of carrageenan elicited an inflammatory response characterized by increase of the paw thickness and infiltration of neutrophils in paw tissues. Histidine, n-acetylcysteine and diclofenac decreased paw thickness, and neutrophil infiltration in the paw tissues. The anti-inflammatory effect induced by co-administration of histidine and n-acetylcysteine with diclofenac, was more than that obtained from histidine and n-acetylcysteine administered alone. The results suggested that histidine, n-acetylcysteine and diclofenac produced anti-inflammatory activities by reducing paw edema and neutrophil infiltrationin induced by carrageenan. Inhibition of cyclooxygenase products such as prostaglandins may be involved in the anti-inflammatory effects induced by histidine and n-acetylcysteine.

  14. Role of transient receptor potential channels in intestinal inflammation and visceral pain: novel targets in inflammatory bowel diseases.

    PubMed

    Zielińska, Marta; Jarmuż, Agata; Wasilewski, Andrzej; Sałaga, Maciej; Fichna, Jakub

    2015-02-01

    Transient receptor potential (TRP) channels are a large group of ion channels that are prevalent in mammalian tissues. They are widely distributed in the central and peripheral nervous systems, and in nonneuronal cells, where they are implicated in sensing temperature, noxious substances, and pain. TRPs play an important role in immune response and nociception and, therefore, may be involved in the pathogenesis of inflammatory bowel diseases, whose major symptoms include chronic inflammatory state and abdominal pain. In this review, we summarize what is known on TRP channels in inflammatory bowel disease and visceral pain; we focus in particular on TRPV1, TRPV4, TRPA1, and TRPM. We also analyze scientific reports that evidence potential use of TRP regulators in future inflammatory bowel disease treatment.

  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. Physiological relevance of food grade microcapsules: Impact of milk protein based microcapsules on inflammation in mouse models for inflammatory bowel diseases.

    PubMed

    Würth, Rebecca; Lagkouvardos, Ilias; Clavel, Thomas; Wilke, Julia; Foerst, Petra; Kulozik, Ulrich; Haller, Dirk; Hörmannsperger, Gabriele

    2015-08-01

    In order to increase beneficial effects of bioactive compounds in functional food and dietary supplements, enormous efforts are put in the technological development of microcapsules. Although these products are often tailor-made for disease susceptible consumer, the physiological impact of microcapsule uptake on the respective target consumer has never been addressed. The present study aimed to assess the relevance of this aspect by analyzing the impact of milk protein based microcapsules on experimental inflammatory bowel disease. Long-term feeding of sodium caseinate or rennet gel microcapsules resulted in significant alterations in the intestinal microbiota of healthy mice. In TNFΔARE/wt mice, a model for chronic ileal inflammation, rennet gel microcapsules resulted in further increased splenomegaly, whereas ileal inflammation was unchanged. In IL10(-/-) mice, a model for chronic colitis, both types of microcapsules induced a local increase of the intestinal inflammation. The present study is the first to demonstrate that, independent of their cargo, microcapsules have the potential to affect the intestinal microbiota and to exert unprecedented detrimental effects on disease-susceptible individuals. In conclusion, the impact of microcapsule uptake on the respective target consumer groups should be thoroughly investigated in advance to their commercial use in functional food or dietary supplements.

  17. Removal of Inflammatory Ascites is Associated with Dynamic Modification of Local and Systemic Inflammation along with Prevention of Acute Lung Injury: In Vivo and In Silico Studies

    PubMed Central

    Emr, Bryanna; Sadowsky, David; Azhar, Nabil; Gatto, Louis A.; An, Gary; Nieman, Gary; Vodovotz, Yoram

    2014-01-01

    Background Sepsis-induced inflammation in the gut/peritoneal compartment occurs early in sepsis, and can lead to acute lung injury (ALI). We have suggested that inflammatory ascites drives the pathogenesis of ALI, and that removal of ascites with an abdominal wound vacuum prevents ALI. We hypothesized that the time- and compartment-dependent changes in inflammation that determine this process can be discerned using Principal Component Analysis (PCA) and Dynamic Bayesian Network (DBN) inference. Methods To test this hypothesis, data from a previous study were analyzed using PCA and DBN. In that study, two groups of anesthetized, ventilated pigs were subjected to experimental sepsis via intestinal ischemia/reperfusion and placement of a peritoneal fecal clot. The Control Group (n=6) had the abdomen opened at 12 hrs post injury (T12) with attachment of a passive drain. The Peritoneal Suction Treatment (PST) Group (n=6) was treated in an identical fashion except that a vacuum was applied to the peritoneal cavity at T12 to remove ascites and maintained until T48. Multiple inflammatory mediators were measured in ascites and plasma and related to lung function (PaO2/FiO2 ratio [PF] and Oxygen Index [OI]) using PCA and DBN. Results PST prevented ALI based on lung histopathology, whereas Control animals developed ALI. Principal Component Analysis revealed that local to the insult (i.e. ascites), primary pro-inflammatory cytokines play a decreased role in the overall response in the treatment group as compared to control. In both groups, multiple, nested positive feedback loops were inferred from DBN, which included interrelated roles for bacterial endotoxin, interleukin-6, transforming growth factor-β1, C-reactive protein, PF, and OI. Von Willebrand Factor was an output in Control, but not PST, ascites. Conclusions These combined in vivo and in silico studies suggest that in this clinically realistic paradigm of sepsis, endotoxin drives the inflammatory response in the

  18. 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

  19. 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. PMID:26936418

  20. Evaluation of anti-nociceptive and anti-inflammatory activity of low-level laser therapy on temporomandibular joint inflammation in rodents.

    PubMed

    Barretto, S R; de Melo, G C; dos Santos, J C; de Oliveira, M G B; Pereira-Filho, R N; Alves, A V F; Ribeiro, M A G; Lima-Verde, I B; Quintans Júnior, L J; de Albuquerque-Júnior, R L C; Bonjardim, L R

    2013-12-01

    The aim of this study was to investigate the analgesic and anti-inflammatory activity of low-level laser therapy (LLLT) on the nociceptive behavioral as well as histomorphological aspects induced by injection of formalin and carrageenan into the rat temporomandibular joint. The 2.5% formalin injection (FRG group) induced behavioral responses characterized by rubbing the orofacial region and flinching the head quickly, which were quantified for 45 min. The pretreatment with systemic administration of diclofenac sodium-DFN group (10 mg/kg i.p.) as well as the irradiation with LLLT infrared (LST group, 780 nm, 70 mW, 30 s, 2.1 J, 52.5 J/cm(2), GaAlAs) significantly reduced the formalin-induced nociceptive responses. The 1% carrageenan injection (CRG group) induced inflammatory responses over the time-course of the study (24 h, and 3 and 7 days) characterized by the presence of intense inflammatory infiltrate rich in neutrophils, scanty areas of liquefactive necrosis and intense interstitial edema, extensive hemorrhagic areas, and enlargement of the joint space on the region. The DFN and LST groups showed an intensity of inflammatory response that was significantly lower than in CRG group over the time-course of the study, especially in the LST group, which showed exuberant granulation tissue with intense vascularization, and deposition of newly formed collagen fibers (3 and 7 days). It was concluded that the LLLT presented an anti-nociceptive and anti-inflammatory response on the inflammation induced in the temporomandibular joint of rodents.

  1. Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro.

    PubMed

    Girol, Ana P; Mimura, Kallyne K O; Drewes, Carine C; Bolonheis, Simone M; Solito, Egle; Farsky, Sandra H P; Gil, Cristiane D; Oliani, Sonia M

    2013-06-01

    Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1(-/-) mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Transcriptional expression of inflammatory mediators in various somatosensory relay centers in the brain of rat models of peripheral mononeuropathy and local inflammation.

    PubMed

    Chamaa, Farah; Chebaro, Maya; Safieh-Garabedian, Bared; Saadeh, Ryan; Jabbur, Suhayl J; Saadé, Nayef E

    2016-08-15

    Contradictory results have been reported regarding the role of inflammatory mediators in the central nervous system in mediating neuropathic pain and inflammatory hyperalgesia following peripheral nerve injury or localized inflammation. The present study aims to correlate between the mRNA expression and protein secretion of proinflammatory cytokines and nerve growth factor (NGF), in the dorsal root ganglia (DRGs), spinal cord, brainstem and thalamus, and pain-related behavior in animal models of peripheral mononeuropathy and localized inflammation. Different groups of rats (n=8, each) were subjected to either lesion of the nerves of their hindpaws to induce mononeuropathy or intraplantar injection of endotoxin (ET) and were sacrificed at various time intervals. TNF-α, IL-1β and NGF mRNA expression and protein levels in the various centers involved in processing nociceptive information were determined, by RT-PCR and ELISA. Control groups were either subjected to sham surgery or to saline injection. Mononeuropathy and ET injection produced significant and sustained increases in the mRNA expression and protein levels of TNF-α, IL-1β and NGF in the ipsilateral and contralateral DRGs, spinal cord, and brainstem. No significant and consistent changes in the mRNA expression of cytokines were noticed in the thalamus, while a downregulation of the NGF-mRNA level was observed. The temporal and spatial patterns of the observed changes in mRNA expression of cytokines and NGF are not closely in phase with the observed allodynia and hyperalgesia in the different models, suggesting that the role of these mediators may not be reduced exclusively to the production and maintenance of pain. PMID:27397080

  10. 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.

  11. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats.

    PubMed

    Badr, Gehan Moustafa; Al-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- α (TNF- α ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin.

  12. The Protective Effect of Aged Garlic Extract on Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Inflammations in Male Albino Rats

    PubMed Central

    Badr, Gehan Moustafa; AL-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  13. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats.

    PubMed

    Badr, Gehan Moustafa; Al-Mulhim, Jawaher Abdulaziz

    2014-01-01

    Natural products have long gained wide acceptance among the public and scientific community in the gastrointestinal ulcerative field. The present study explore the potential effects of aged garlic extract (AGE) on indomethacin-(IN-) induced gastric inflammation in male rats. Animals were divided into six groups (n = 8) control group, IN-induced gastric inflammation group via oral single dose (30 mg/kg to fasted rats) two AGE orally administered groups (100 and 200 mg/kg for 30 consecutive days) two AGE orally administered groups to rats pretreated with IN at the same aforementioned doses. The results declared the more potent effect of the higher AGE dose (200 mg/kg) as compared to that of the 100 mg/kg dose in the gastroprotective effects reflected by significant gastric mucosal healing of damage and reduction in the total microbial induced due to indomethacin administration. In addition to the significant effect to normalize the significant increase in malondialdehyde (MDA), myeloperoxidase (MPO), tumor necrosis factor- α (TNF- α ) values, and the significant decrease in the total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) values induced by indomethacin. The results support AGE antioxidant, anti-inflammatory, and antimicrobial potency reflected by the healing of the gastric tissue damage induced by indomethacin. PMID:24876878

  14. Colonic ornithine decarboxylase in inflammatory bowel disease: ileorectal activity gradient, guanosine triphosphate stimulation, and association with epithelial regeneration but not the degree of inflammation and clinical features.

    PubMed

    Allgayer, Hubert; Roisch, Ulla; Zehnter, Elmar; Ziegenhagen, Dieter J; Dienes, Hans P; Kruis, Wolfgang

    2007-01-01

    The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn's disease, 17 with ulcerative colitis) and 29 controls, using the amount of 14CO2 liberated from (carboxyl-14C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 micromol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn's disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP

  15. 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.

  16. 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

    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

  17. 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

  18. 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. PMID:24386404

  19. Suppression of Molecular Inflammatory Pathways by Toll-Like Receptor 7, 8, and 9 Antagonists in a Model of IL-23-Induced Skin Inflammation

    PubMed Central

    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. PMID:24386404

  20. 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.

  1. 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

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

    PubMed

    Wang, Minjun; Tang, Wenbo; 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

  3. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-08-29

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.

  4. 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

  5. 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. PMID:25554116

  6. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.

    PubMed

    Calabriso, Nadia; Massaro, Marika; Scoditti, Egeria; Pellegrino, Mariangela; Ingrosso, Ilaria; Giovinazzo, Giovanna; Carluccio, Maria Annunziata

    2016-01-01

    Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. PMID:27589705

  7. 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

  8. Evaluation and Comparison of the Biopathology of Collagen and Inflammation in the Extracellular Matrix of Oral Epithelial Dysplasias and Inflammatory Fibrous Hyperplasia Using Picrosirius Red Stain and Polarising Microscopy: A Preliminary Study

    PubMed Central

    Varghese, Soma Susan; Sarojini, Sreenivasan Bargavan; George, Giju Baby; Vinod, Sankar; Mathew, Philips; Babu, Anulekh; Sebastian, Joseph

    2015-01-01

    Background: The role of tumour inflammation and the dysplastic epithelial-stromal interactions on the nature of collagen fibres in the extracellular matrix of dysplastic epithelium is not fully understood. The present study was aimed to evaluate and compare the inflammation and pathological stromal collagen (loosely packed thin disorganized collagen) present in mild, moderate and severe epithelial dysplasias with that of inflammatory fibrous hyperplasias. The basement membrane intactness of epithelial dysplasias was also evaluated to determine if dysplastic epithelial mesenchymal interaction has any role in the integrity of stromal collagen in epithelial dysplasia. Methods: Oral epithelial dysplasias, inflammatory fibrous hyperplasia and normal oral mucosal samples were used for the study. Packing, thickness and orientation of collagen fibres in mild, moderate and severe grades of oral epithelial dysplasias (n = 24), inflammatory fibrous hyperplasia (n = 8) and normal oral mucosal samples (n = 8) were analysed based on the polarisation of collagen fibres in picrosirius red polarising stain under polarising microscope. Results: All the grades of epithelial dysplasias showed greenish yellow birefringence confirming the presence of loosely arranged pathological collagen in the presence of moderate inflammation. All the cases of inflammatory fibrous hyperplasia showed red polarisation hue and moderate inflammation. A statistically significant difference was found in the packing and orientation of collagen when epithelial dysplasias and inflammatory fibrous hyperplasia were compared (P < 0.01). When the intactness of basement membrane integrity was compared in all the groups of epithelial dysplasia, a statistically significant result was obtained (P < 0.05). Conclusions: Presence of significant amount of loosely packed thin disoriented collagen even in mild epithelial dysplasia suggests that tumourigenic factors are released to connective tissue stroma much earlier than

  9. 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

  10. 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.

  11. Identification of CD68(+) neutrophil granulocytes in in vitro model of acute inflammation and inflammatory bowel disease.

    PubMed

    Amanzada, Ahmad; Malik, Ihtzaz Ahmed; Blaschke, Martina; Khan, Sajjad; Rahman, Hazir; Ramadori, Giuliano; Moriconi, Federico

    2013-01-01

    CD-68 is widely regarded as a selective marker for human monocytes and macrophages and is commonly used in human pathology studies. The purpose of this study was to investigate the expression of CD-68 in human peripheral blood mononuclear cells (PBMCs), neutrophil granulocytes (NGs) and in inflamed intestinal tissue samples for comparison. PBMCs and NGs were isolated from heparinized human blood samples. Intestinal biopsies were obtained during routine endoscopic procedures from patients with inflammatory bowel disease (IBD), e.g. ulcerative colitis and Crohn's disease. Gene and protein expression was analyzed by real-time RT-PCR, Western blot and immunohistochemistry. Both PBMCs and NGs preparations contained cells that were positive for CD-68 and either neutrophil elastase (NE), or myeloperoxidase (MPO). CD-68(+)/NE(-)/MPO(-) cells were regarded as monocytes. CD-68 mRNA expression was detected in PBMCs and NGs preparations. With Western blot and by performing immunoprecipitation of cell lysate, we could clearly detect CD-68 in NGs, U-937, THP-1, Hep-G2, Jurkat cells and PBMCs. Identification of inflammatory cells in acutely inflamed colonic mucosa obtained from patients with IBD revealed a strong accumulation of CD-68(+)/MPO(+) cells compared to normal colonic mucosa. The uptake of the marker by phagocytosis was excluded by performing a double staining with CD-163/NE and CD-163/MPO in PBMCs, NGs cultures and in inflamed colonic mucosa. These results identify CD-68(+) NGs in peripheral blood and inflamed colonic mucosa. CD-68 is not only a marker for the macrophages-monocytes but also for NGs.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. [Inflammation and diabetes].

    PubMed

    Löbner, K; Füchtenbusch, M

    2004-09-01

    The focus of current diabetes research is the clarification of the pathogenetic relationships between subclinical inflammation, diabetes and arteriosclerosis. Even minimal disturbances in glucose tolerance are associated with a chronic, generalized inflammatory reaction that links components of the metabolic syndrome and contributes to the development of diabetic complications as well as to the development and progression of arteriosclerosis. The most important mediators and markers of this inflammation cascade are NF-kappaB, TNF-alpha, IL-6, CRP and PAI-1. For the treatment of subclinical inflammation, substances with anti-inflammatory properties such as statins or ACE inhibitors are of increasing importance.

  17. M2 Macrophage Polarization Mediates Anti-inflammatory Effects of Endothelial Nitric Oxide Signaling

    PubMed Central

    Lee, Woo Je; Tateya, Sanshiro; Cheng, Andrew M.; Rizzo-DeLeon, Norma; Wang, Nicholas F.; Handa, Priya; Wilson, Carole L.; Clowes, Alexander W.; Sweet, Ian R.; Bomsztyk, Karol; Schwartz, Michael W.

    2015-01-01

    Endothelial nitric oxide (NO) signaling plays a physiological role in limiting obesity-associated insulin resistance and inflammation. This study was undertaken to investigate whether this NO effect involves polarization of macrophages toward an anti-inflammatory M2 phenotype. Mice with transgenic endothelial NO synthase overexpression were protected against high-fat diet (HFD)-induced hepatic inflammation and insulin resistance, and this effect was associated with reduced proinflammatory M1 and increased anti-inflammatory M2 activation of Kupffer cells. In cell culture studies, exposure of macrophages to endothelial NO similarly reduced inflammatory (M1) and increased anti-inflammatory (M2) gene expression. Similar effects were induced by macrophage overexpression of vasodilator-stimulated phosphoprotein (VASP), a key downstream mediator of intracellular NO signaling. Conversely, VASP deficiency induced proinflammatory M1 macrophage activation, and the transplantation of bone marrow from VASP-deficient donor mice into normal recipients caused hepatic inflammation and insulin resistance resembling that induced in normal mice by consumption of an HFD. These data suggest that proinflammatory macrophage M1 activation and macrophage-mediated inflammation are tonically inhibited by NO → VASP signal transduction, and that reduced NO → VASP signaling is involved in the effect of HFD feeding to induce M1 activation of Kupffer cells and associated hepatic inflammation. Our data implicate endothelial NO → VASP signaling as a physiological determinant of macrophage polarization and show that signaling via this pathway is required to prevent hepatic inflammation and insulin resistance. PMID:25845662

  18. 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

  19. Nitric oxide and peroxynitrite production in ocular inflammation.

    PubMed Central

    Allen, J B; Keng, T; Privalle, C

    1998-01-01

    Recent studies have implicated nitric oxide and peroxynitrite in the pathogenesis of many diseases, such as septic shock, arthritis, lung disease, and atherosclerosis. Nitric oxide (.NO) exerts many diverse effects on vascular tone, affecting neurotransmission and cellular cytotoxicity/communication. Our laboratory and others have documented a proinflammatory role for .NO in ocular inflammation. Uveitis, which is an inflammation of the highly vascular uveal tract in the eye, is a debilitating condition that can lead to visual impairment and blindness. It is characterized by acute, recurrent, or persistent inflammation with disruption of the blood-aqueous barrier and is accompanied by protein leakage and leukocyte infiltration into the aqueous humor and anterior chamber. Systemic injection of endotoxin into mice and rats, or intraocular injection of endotoxin into mice, rats, and rabbits induces acute uveitis, which clinically and histologically resembles acute anterior uveitis in humans. These models facilitate the study of pathogenic mechanisms that contribute to ocular inflammation. In addition to .NO, superoxide anion radicals (O2.-), and peroxynitrite (ONOO-), the products of the reaction between .NO and O2.-, are also implicated in uveitis. The role of peroxynitrite in ocular inflammation is still largely unknown. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information critical to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic intervention(s) can be developed. PMID:9788889

  20. 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

    2016-09-01

    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.

  1. Anti-inflammatory actions of Chemoattractant Receptor-homologous molecule expressed on Th2 by the antagonist MK-7246 in a novel rat model of Alternaria alternata elicited pulmonary inflammation.

    PubMed

    Gil, Malgorzata A; Caniga, Michael; Woodhouse, Janice D; Eckman, Joseph; Lee, Hyun-Hee; Salmon, Michael; Naber, John; Hamilton, Valerie T; Sevilla, Raquel S; Bettano, Kimberly; Klappenbach, Joel; Moy, Lily; Correll, Craig C; Gervais, Francois G; Siliphaivanh, Phieng; Zhang, Weisheng; Zhang-Hoover, Jie; McLeod, Robbie L; Cicmil, Milenko

    2014-11-15

    Alternaria alternata is a fungal allergen linked to the development of severe asthma in humans. In view of the clinical relationship between A. alternata and asthma, we sought to investigate the allergic activity of this antigen after direct application to the lungs of Brown Norway rats. Here we demonstrate that a single intratracheal instillation of A. alternata induces dose and time dependent eosinophil influx, edema and Type 2 helper cell cytokine production in the lungs of BN rats. We established the temporal profile of eosinophilic infiltration and cytokine production, such as Interleukin-5 and Interleukin-13, following A. alternata challenge. These responses were comparable to Ovalbumin induced models of asthma and resulted in peak inflammatory responses 48h following a single challenge, eliminating the need for multiple sensitizations and challenges. The initial perivascular and peribronchiolar inflammation preceded alveolar inflammation, progressing to a more sub-acute inflammatory response with notable epithelial cell hypertrophy. To limit the effects of an A. alternata inflammatory response, MK-7246 was utilized as it is an antagonist for Chemoattractant Receptor-homologous molecule expressed in Th2 cells. In a dose-dependent manner, MK-7246 decreased eosinophil influx and Th2 cytokine production following the A. alternata challenge. Furthermore, therapeutic administration of corticosteroids resulted in a dose-dependent decrease in eosinophil influx and Th2 cytokine production. Reproducible asthma-related outcomes and amenability to pharmacological intervention by mechanisms relevant to asthma demonstrate that an A. alternata induced pulmonary inflammation in BN rats is a valuable preclinical pharmacodynamic in vivo model for evaluating the pharmacological inhibitors of allergic pulmonary inflammation.

  2. Kuttner's tumor of salivary glands resembling marginal zone B-cell lymphoma of the MALT type: a histopathologic and immunohistochemical study of 7 cases.

    PubMed

    Kojima, Masaru; Nakamura, Shigeo; Itoh, Hideaki; Yamane, Yuko; Shimizu, Kazuhiko; Masawa, Nobuhide

    2004-10-01

    Kuttner's tumor is a benign inflammatory process of the submandibular gland that presents as a hard mass mimicking a malignant neoplasm clinically. The histologic feature varies according to stage of evolution and severity of inflammation. We report here 7 cases of Kuttner's tumor that morphologically resemble primary salivary gland marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Histologically, the lobular architecture was distorted and the septa showed sclerosis. There was a dense lymphoplasmacytoid infiltration with lymphoid follicle formation accompanied by loss of acini and ducts. In 4 cases, a few salivary gland ducts contained the lymphoid cells within the epithelium. However, a true lymphoepithelial lesion was observed in none of the 7 cases. Immunohistochemical study demonstrated a disrupted follicular dendritic cell network, which is a characteristic finding of follicular colonization of MALT-type lymphoma. In 6 cases, there were a few small foci of lymphocytes somewhat resembling centrocyte-like cells of MALT-type lymphoma. However, immunohistological study demonstrated the mixed nature of the cells resembling centrocyte-like cells. Moreover, the polytypic nature of B lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction.

  3. Orbital inflammation: Corticosteroids first.

    PubMed

    Dagi Glass, Lora R; Freitag, Suzanne K

    2016-01-01

    Orbital inflammation is common, and may affect all ages and both genders. By combining a thorough history and physical examination, targeted ancillary laboratory testing and imaging, a presumptive diagnosis can often be made. Nearly all orbital inflammatory pathology can be empirically treated with corticosteroids, thus obviating the need for histopathologic diagnosis prior to initiation of therapy. In addition, corticosteroids may be effective in treating concurrent systemic disease. Unless orbital inflammation responds atypically or incompletely, patients can be spared biopsy.

  4. Inflammation and cancer

    PubMed Central

    Coussens, Lisa M.; Werb, Zena

    2009-01-01

    Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development. PMID:12490959

  5. Laing distal myopathy pathologically resembling inclusion body myositis

    PubMed Central

    Roda, Ricardo H; Schindler, Alice B; Blackstone, Craig; Mammen, Andrew L; Corse, Andrea M; Lloyd, Thomas E

    2014-01-01

    Mutations in MYH7 cause autosomal dominant Laing distal myopathy. We present a family with a previously reported deletion (c.5186_5188delAGA, p.K1729del). Muscle pathology in one family member was characterized by an inflammatory myopathy with rimmed vacuoles, increased MHC Class I expression, and perivascular and endomysial muscle inflammation comprising CD3+, CD4+, CD8+, and CD68+ inflammatory cells. Interestingly, this biopsy specimen contained TDP-43, p62, and SMI-31-positive protein aggregates typical of inclusion body myositis. These findings should alert physicians to the possibility that patients with MYH7 mutations may have muscle biopsies showing pathologic findings similar to inclusion body myositis. PMID:25574480

  6. 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 ...

  7. Coagulation inhibitors in inflammation.

    PubMed

    Esmon, C T

    2005-04-01

    Coagulation is triggered by inflammatory mediators in a number of ways. However, to prevent unwanted clot formation, several natural anticoagulant mechanisms exist, such as the antithrombin-heparin mechanism, the tissue factor pathway inhibitor mechanism and the protein C anticoagulant pathway. This review examines the ways in which these pathways are down-regulated by inflammation, thus limiting clot formation and decreasing the natural anti-inflammatory mechanisms that these pathways possess. PMID:15787615

  8. Phosphorylation of Akt Mediates Anti-Inflammatory Activity of 1-p-Coumaroyl β-D-Glucoside Against Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells

    PubMed Central

    Vo, Van Anh; Lee, Jae-Won; Kim, Ji-Young; Park, Jun-Ho; Lee, Hee Jae; Kim, Sung-Soo; Kwon, Yong-Soo

    2014-01-01

    Hydroxycinnamic acids have been reported to possess numerous pharmacological activities such as antioxidant, anti-inflammatory, and anti-tumor properties. However, the biological activity of 1-p-coumaroyl β-D-glucoside (CG), a glucose ester derivative of p-coumaric acid, has not been clearly examined. The objective of this study is to elucidate the anti-inflammatory action of CG in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. In the present study, CG significantly suppressed LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE2 and the protein expression of iNOS and COX-2. CG also inhibited LPS-induced secretion of pro-inflammatory cytokines, IL-1β and TNF-α. In addition, CG significantly suppressed LPS-induced degradation of IκB. To elucidate the underlying mechanism by which CG exerts its anti-inflammatory action, involvement of various signaling pathways were examined. CG exhibited significantly increased Akt phosphorylation in a concentration-dependent manner, although MAPKs such as Erk, JNK, and p38 appeared not to be involved. Furthermore, inhibition of Akt/PI3K signaling pathway with wortmannin significantly, albeit not completely, abolished CG-induced Akt phosphorylation and anti-inflammatory actions. Taken together, the present study demonstrates that Akt signaling pathway might play a major role in CG-mediated anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells. PMID:24634601

  9. Inflammatory Myopathies.

    PubMed

    Atluri, Rama Bandlamudi

    2016-01-01

    Idiopathic inflammatory myopathies are relatively rare diseases. Polymyositis and dermatomyositis are more common in women than men (2:1 ratio), while inclusion body myositis is twice as common in men. Inflammatory myopathies are a heterogeneous group of chronic systemic autoimmune diseases with an annual incidence of two to five cases per million, characterized by muscle inflammation and progressive muscle weakness. There are three major diseases which includes Dermatomyositis (DM) including a distinct juvenile subtype (JDM), Polymyositis (PM), and Inclusion Body Myositis. DM is a compliment mediated microangiopathy affecting skin and muscle. PM and IBM are T-cell mediated disorders, where CD8 positive cytotoxic T cells invade muscle fibers expressing MHC class I antigens, this leading to fiber necrosis. In IBM, vacuolar formation with amyloid deposits are also present. This article summarizes the clinical, histochemical and immunological features as well as the treatment options of the inflammatory myopathies. PMID:27311223

  10. Increased function of the TRPV1 channel in small sensory neurons after local inflammation or in vitro exposure to the pro-inflammatory cytokine GRO/KC

    PubMed Central

    Dong, Fei; Du, Yi-Ru; Xie, Wenrui; Strong, Judith A.; He, Xi-Jing; Zhang, Jun-Ming

    2012-01-01

    Objective Inflammation at the level of the sensory dorsal root ganglia (DRG) leads to robust mechanical pain behaviors and the local inflammation has direct excitatory effects on sensory neurons including small, primarily nociceptive, neurons. These neurons express the TRPV1 channel, which integrates multiple signals of pain and inflammation. The aim of this study was to characterize regulation of the TRPV1 channel by local DRG inflammation and by GRO/KC (CXCL1), a cytokine known to be upregulated in inflamed DRGs. Methods Activation of the TRPV1 receptor with capsaicin was studied with patch clamp methods in acutely isolated small diameter rat sensory neurons in primary culture. In vivo, behavioral effects of TRPV1 and GRO/KC were examined by paw injections. Results Neurons isolated from lumbar DRGs 3 days after local inflammation showed enhanced TRPV1 function: tachyphylaxis (the decline in response to repeated applications of capsaicin) was significantly reduced. A similar effect on tachyphylaxis was observed in neurons pre-treated for 4 hours in vitro with GRO/KC. This effect was blocked by H-89, a protein kinase A inhibitor. Consistent with the in vitro results, in vivo behavioral responses to paw injection of capsaicin were enhanced and prolonged by pre-injecting the paw with GRO/KC 4 hours before the capsaicin injection. GRO/KC paw injections alone did not elicit pain behaviors. Conclusions Function of the TRPV1 channel is enhanced by DRG inflammation and these effects are preserved in vitro during short-term culture. The effects (decreased tachyphylaxis) are mimicked by incubation with GRO/KC, which has previously been found to be strongly upregulated in this and other pain models. PMID:22466126

  11. [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.

  12. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock.

    PubMed

    Wheatley, Carmen

    2006-01-01

    Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock. PMID:16545917

  13. Social perception of facial resemblance in humans.

    PubMed

    DeBruine, Lisa M; Jones, Benedict C; Little, Anthony C; Perrett, David I

    2008-02-01

    Two lines of reasoning predict that highly social species will have mechanisms to influence behavior toward individuals depending on their degree of relatedness. First, inclusive fitness theory leads to the prediction that organisms will preferentially help closely related kin over more distantly related individuals. Second, evaluation of the relative costs and potential benefits of inbreeding suggests that the degree of kinship should also be considered when choosing a mate. In order to behaviorally discriminate between individuals with different levels of relatedness, organisms must be able to discriminate cues of kinship. Facial resemblance is one such potential cue in humans. Computer-graphic manipulation of face images has made it possible to experimentally test hypotheses about human kin recognition by facial phenotype matching. We review recent experimental evidence that humans respond to facial resemblance in ways consistent with inclusive fitness theory and considerations of the costs of inbreeding, namely by increasing prosocial behavior and positive attributions toward self-resembling images and selectively tempering attributions of attractiveness to other-sex faces in the context of a sexual relationship.

  14. Social perception of facial resemblance in humans.

    PubMed

    DeBruine, Lisa M; Jones, Benedict C; Little, Anthony C; Perrett, David I

    2008-02-01

    Two lines of reasoning predict that highly social species will have mechanisms to influence behavior toward individuals depending on their degree of relatedness. First, inclusive fitness theory leads to the prediction that organisms will preferentially help closely related kin over more distantly related individuals. Second, evaluation of the relative costs and potential benefits of inbreeding suggests that the degree of kinship should also be considered when choosing a mate. In order to behaviorally discriminate between individuals with different levels of relatedness, organisms must be able to discriminate cues of kinship. Facial resemblance is one such potential cue in humans. Computer-graphic manipulation of face images has made it possible to experimentally test hypotheses about human kin recognition by facial phenotype matching. We review recent experimental evidence that humans respond to facial resemblance in ways consistent with inclusive fitness theory and considerations of the costs of inbreeding, namely by increasing prosocial behavior and positive attributions toward self-resembling images and selectively tempering attributions of attractiveness to other-sex faces in the context of a sexual relationship. PMID:18157627

  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. 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.

  17. 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

  18. 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

  19. Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation.

    PubMed

    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

  20. 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. PMID:17893694

  1. Inflammatory Bowel Disease.

    PubMed

    2016-01-01

    Inflammation response plays an important role in host survival, and it also leads to acute and chronic inflammatory diseases such as rheumatoid arthritis, bowel diseases, allergic rhinitis, asthma, atopic dermatitis and various neurodegenerative diseases. During the course of inflammation, the ROS level increases. In addition to ROS, several inflammatory mediators produced at the site lead to numerous cell-mediated damages. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal disorder resulting from a dysfunctional epithelial, innate and adaptive immune response to intestinal microorganisms. The methods involving indomethacin-induced enterocolitis in rats with macroscopic changes of IBD, myeloperoxidase assay, microscopic (histologic) characters and biochemical parameters are discussed.

  2. Familial resemblance for serum metabolite concentrations.

    PubMed

    Draisma, Harmen H M; Beekman, Marian; Pool, René; van Ommen, Gert-Jan B; Adamski, Jerzy; Prehn, Cornelia; Vaarhorst, Anika A M; de Craen, Anton J M; Willemsen, Gonneke; Slagboom, P Eline; Boomsma, Dorret I

    2013-10-01

    Metabolomics is the comprehensive study of metabolites, which are the substrates, intermediate, and end products of cellular metabolism. The heritability of the concentrations of circulating metabolites bears relevance for evaluating their suitability as biomarkers for disease. We report aspects of familial resemblance for the concentrations in human serum of more than 100 metabolites, measured using a targeted metabolomics platform. Age- and sex-corrected monozygotic twin correlations, midparent-offspring regression coefficients, and spouse correlations in subjects from two independent cohorts (Netherlands Twin Register and Leiden Longevity Study) were estimated for each metabolite. In the Netherlands Twin Register subjects, who were largely fasting, we found significant monozygotic twin correlations for 121 out of 123 metabolites. Heritability was confirmed by midparent-offspring regression. For most detected metabolites, the correlations between spouses were considerably lower than those between twins, indicating a contribution of genetic effects to familial resemblance. Remarkably high heritability was observed for free carnitine (monozygotic twin correlation 0.66), for the amino acids serine (monozygotic twin correlation 0.77) and threonine (monozygotic twin correlation 0.64), and for phosphatidylcholine acyl-alkyl C40:3 (monozygotic twin correlation 0.77). For octenoylcarnitine, a consistent point estimate of approximately 0.50 was found for the spouse correlations in the two cohorts as well as for the monozygotic twin correlation, suggesting that familiality for this metabolite is explained by shared environment. We conclude that for the majority of metabolites targeted by the used metabolomics platform, the familial resemblance of serum concentrations is largely genetic. Our results contribute to the knowledge of the heritability of fasting serum metabolite concentrations, which is relevant for biomarker research. PMID:23985338

  3. Characterization of basal and re-inflammation-associated long-term alteration in pain responsivity following short-lasting neonatal local inflammatory insult.

    PubMed

    Ren, K; Anseloni, V; Zou, S-P; Wade, E B; Novikova, S I; Ennis, M; Traub, R J; Gold, M S; Dubner, R; Lidow, M S

    2004-08-01

    Recently, several studies have suggested that neonatal noxious insult could alter future responses to painful stimuli. However, the manifestations, mechanisms, and even developmental nature of these alterations remain a matter of controversy. In part, this is due to the lack of detailed information on the neonatal sensitive period(s) during which noxious stimulation influences future nociception, and the time-course and distribution of the resultant abnormalities. The present paper describes these parameters in a rat model of short-lasting ( approximately 24 h) neonatal local inflammation of a hindpaw produced by injection of 0.25% carrageenan (1 microl/g). Examinations of paw withdrawal responses to thermal and mechanical stimulations in adult animals, which as neonates were subjected to this insult, showed that the previously-reported long-term hypoalgesia and hyperalgesia are not mutually exclusive outcomes of early noxious experience. Long-term hypoalgesia was apparent at the basal conditions and was equally strong in the previously injured and uninjured paws, which suggests a globally-driven deficit. In contrast, long-term excessive hyperalgesia had the strongest manifestation in the neonatally-injured paw after re-inflammation, indicating significant segmental involvement in its generation. The differences between mechanisms underlying the observed hypoalgesia and hyperalgesia are further underscored by the finding that, while the former is detectable only after animals reach the second month of life, the latter is elicitable immediately upon cessation of the initial neonatal inflammation. Nevertheless, we detected a significant overlap in the neonatal sensitive periods for generation of these effects (both occurring within the first postnatal week). Also, neither the basal hypoalgesia nor excessive re-inflammation-associated hyperalgesia subsided with age and were detectable in 120-125-day-old rats. These finding provide a framework within which the entire

  4. HIV-1 Superinfection Resembles Primary Infection

    PubMed Central

    Sheward, Daniel J.; Ntale, Roman; Garrett, Nigel J.; Woodman, Zenda L.; Abdool Karim, Salim S.; Williamson, Carolyn

    2015-01-01

    The relevance of superinfection as a model to identify correlates of protection against human immunodeficiency virus (HIV) depends on whether the superinfecting transmission resembles primary infection, which has not been established. Here, we characterize the genetic bottleneck in superinfected individuals for the first time. In all 3 cases, superinfection produced a spike in viral load and could be traced to a single, C-C chemokine receptor 5–tropic founder virus with shorter, less glycosylated variable regions than matched chronic viruses. These features are consistent with primary HIV transmission and provide support for the use of superinfection as a model to address correlates of protection against HIV. PMID:25754982

  5. 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

  6. [Free radicals and eye inflammations].

    PubMed

    Ianopol, N

    1998-01-01

    Free radicals (FR), mainly those oxygen derived (FRO) are considered to be inflammation's mediators. Produced either by photochemical reactions or by synthesis into active phagocytic cells (in the cellular time of inflammation), FRO can determine an inflammatory reaction or they can augment a pre-existed one. These phenomena are produced by synthesis of inflammation's mediators as: prostaglandines, prostaciclines, thromboxane and leucotrienes starting from arachidonic acid, by the generation of some compounds with chemotactic properties and by the activation of phagocytic cells, by the augmentation of the proteolytic activity due to natural protease inhibitors inactivation and, last but not least, by the directly destructive action against different tissue compounds. In the first part of this lecture I presented general data about FR, inflammation, photosensitive agents and radical reactions. In the second part, I presented the pathogenic relation between FR and ocular inflammations from two different point of view: that of inflammation generation by FR, and that of FR generation during a preexistent inflammation.

  7. Aging reverses the role of the transient receptor potential vanilloid-1 channel in systemic inflammation from anti-inflammatory to proinflammatory

    PubMed Central

    Wanner, Samuel P; Garami, Andras; Pakai, Eszter; Oliveira, Daniela L; Gavva, Narender R; Coimbra, Cândido C

    2012-01-01

    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. PMID:22214765

  8. Inflammation and hemostasis: a bidirectional interaction.

    PubMed

    Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe

    2007-01-01

    There is increasing evidence that inflammation is a potent activator of coagulation pathways. In fact, inflammatory mediators upregulate procoagulant factors, inhibit endogenous anticoagulants and attenuate fibrinolytic response. In addition, systemic inflammation appears to increase platelet reactivity. However, the interaction between these two systems is bidirectional as coagulation is also capable of modulating inflammatory activity. This review focuses on the current understanding of the complex interactions between inflammation and coagulation.

  9. 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. PMID:26400429

  10. Points of control in inflammation

    NASA Astrophysics Data System (ADS)

    Nathan, Carl

    2002-12-01

    Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.

  11. Regulation of CYP1A1 and Inflammatory Cytokine by NCOA7 Isoform 4 in Response to Dioxin Induced Airway Inflammation

    PubMed Central

    Cho, Sung-Hwan; Park, Shin Young; Lee, Eun Jeong; Cho, Yo Han; Park, Hyun Sun; Hong, Seok-Ho

    2015-01-01

    Background Aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, binds to a wide variety of synthetic and naturally occurring compounds. AhR is involved in the regulation of inflammatory response during acute and chronic respiratory diseases. We investigated whether nuclear receptor coactivator 7 (NCOA7) could regulate transcriptional levels of AhR target genes and inflammatory cytokines in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated human bronchial epithelial cells. This study was based on our previous study that NCOA7 was differentially expressed between normal and chronic obstructive pulmonary disease lung tissues. Methods BEAS-2B and A549 cells grown under serum-free conditions were treated with or without TCDD (0.15 nM and 6.5 nM) for 24 hours after transfection of pCMV-NCOA7 isoform 4. Expression levels of cytochrome P4501A1 (CYP1A1), IL-6, and IL-8 were measured by quantitative real-time polymerase chain reaction. Results The transcriptional activities of CYP1A1 and inflammatory cytokines were strongly induced by TCDD treatment in both BEAS-2B and A549 cell lines. The NCOA7 isoform 4 oppositely regulated the transcriptional activities of CYP1A1 and inflammatory cytokines between BEAS-2B and A549 cell lines. Conclusion Our results suggest that NCOA7 could act as a regulator in the TCDD-AhR signaling pathway with dual roles in normal and abnormal physiological conditions. PMID:25861343

  12. 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.

  13. Parasagittal solitary fibrous tumor resembling hemangiopericytoma.

    PubMed

    Shidoh, Satoka; Yoshida, Kazunari; Takahashi, Satoshi; Mikami, Shuji; Mukai, Makio; Kawase, Takeshi

    2010-04-01

    Solitary fibrous tumor (SFT) is a rare mesenchymal tumor in the central nervous system, and the clinical behavior of this tumor is similar to that of meningioma. We report the case of a Japanese woman with parasagittal SFT that resembled hemangiopericytoma (HPC). Histological examination revealed that the tumor was highly cellular, with cells containing oval- or spindle-shaped nuclei arranged in sheets or a pattern-less growth mode. Focal vascular proliferation was also observed. Some areas showed intercellular stroma containing remarkable eosinophilic collagens. Tumor cells showed a strong immunoreactivity for CD34 but were negative for S-100 protein and epithelial membrane antigen. MIB-1 labeling index of the tumor was 6.6%. Owing to the high cellularity, high MIB-1 labeling index, and focal vascular proliferation, it was difficult to distinguish this lesion from HPC. However, the tumor was finally diagnosed as SFT on the basis of the strong immunostaining for CD34 and absence of pericellular reticulin.

  14. 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

  15. Quercetin, Inflammation and Immunity.

    PubMed

    Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

    2016-03-01

    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. α-Lipoic acid has anti-inflammatory and anti-oxidative properties: an experimental study in rats with carrageenan-induced acute and cotton pellet-induced chronic inflammations.

    PubMed

    Odabasoglu, Fehmi; Halici, Zekai; Aygun, Hayati; Halici, Mesut; Atalay, Fadime; Cakir, Ahmet; Cadirci, Elif; Bayir, Yasin; Suleyman, Halis

    2011-01-01

    α-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily absorbed and bioavailable compound capable of scavenging a number of free radicals, and it has been used for treating diseases in which oxidative stress plays a major role. The present study was designed to gain a better understanding for the positive effects of ALA on the models of acute and chronic inflammation in rats, and also determine its anti-oxidative potency. In an acute model, three doses of ALA (50, 100 and 200 mg/kg) and one dose of indomethacin (25 mg/kg) or diclofenac (25 mg/kg) were administered to rats by oral administration. The paw volumes of the animals were calculated plethysmometrically, and 0·1 ml of 1 % carrageenan (CAR) was injected into the hind paw of each animal 1 h after oral drug administration. The change in paw volume was detected as five replicates every 60 min by plethysmometry. In particular, we investigated the activities of catalase, superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited anti-inflammatory effects on both acute and chronic inflammations, and a strongly anti-oxidative potency on linoleic acid oxidation. Moreover, the administration of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity, (3) the increases of GST and iNOS activities and the amount of LPO and (4) the decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion, these results suggest that the anti-inflammatory properties of ALA, which has a strong anti-oxidative potency, could be related to its positive effects on the antioxidant system in a variety of tissues in rats.

  17. [COPD: bronchial and systemic inflammation].

    PubMed

    Macario, Ciro Casanova; de Torres Tajes, Juan Pablo; Córdoba Lanus, Elizabeth

    2010-01-01

    Chronic obstructive pulmonary disease (COPD) is considered to be an inflammatory disease of the airways, in which there can be low-grade systemic inflammation. The etiology of this disease is multifactorial but is mainly due to an anomalous and amplified inflammatory response to tobacco smoke. This inflammatory response involves innate and acquired immunity. The latter is characterized by a Th1-type (CD8) response and its presence seems to be associated with progression to advanced stages of the disease. Currently, it is unknown whether bronchial and systemic inflammation are related or whether they act as independent compartments. Most of the available data on COPD are drawn from cross-sectional studies and consequently a causal relation between the possible inflammatory mediators and the genetic factors involved in pulmonary and extrapulmonary involvement in this disease cannot be established. Further studies are required that would allow the inflammatory response to be correlated with the distinct COPD phenotypes.

  18. Inflammatory networks underlying colorectal cancer.

    PubMed

    Lasry, Audrey; Zinger, Adar; Ben-Neriah, Yinon

    2016-03-01

    Inflammation is emerging as one of the hallmarks of cancer, yet its role in most tumors remains unclear. Whereas a minority of solid tumors are associated with overt inflammation, long-term treatment with non-steroidal anti-inflammatory drugs is remarkably effective in reducing cancer rate and death. This indicates that inflammation might have many as-yet-unrecognized facets, among which an indolent course might be far more prevalent than previously appreciated. In this Review, we explore the various inflammatory processes underlying the development and progression of colorectal cancer and discuss anti-inflammatory means for its prevention and treatment.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Adrenal Cushing's syndrome may resemble eating disorders.

    PubMed

    Hatakeyama, Makiko; Nakagami, Taku; Yasui-Furukori, Norio

    2014-01-01

    We encountered a patient who presented extreme weight loss and received an eating disorder diagnosis that was later identified as adrenal Cushing's syndrome. A 32-year-old woman with a 2-year history of an eating disorder was admitted to our psychiatric ward due to dehydration, malnutrition and low weight. Her height and body weight were 152.1 cm and 29.8 kg, respectively (body mass index: 12.8). Her other symptoms included a depressed mood, decreased interest, retardation and suicidal ideation. Standard medical cares were prescribed to treat the depressive symptoms and eating disorder, but the depressive episode and low body weight of the patient persisted. Computed tomography of the abdomen revealed an unexpected left adrenal gland tumor. Cushing's syndrome was diagnosed based on several endocrinological examinations. After an enucleation of the left adrenal gland tumor, the patient began eating, and her body weight increased gradually. Her body weight increased to 42.0-47.0 kg (body mass index: 18.2-20.3). Her mental and physical conditions had stabilized. This case suggests that adrenal Cushing's syndrome may resemble eating disorders.

  4. Inflammation induced loss of skeletal muscle.

    PubMed

    Londhe, Priya; Guttridge, Denis C

    2015-11-01

    Inflammation is an important contributor to the pathology of diseases implicated in skeletal muscle dysfunction. A number of diseases and disorders including inflammatory myopathies and Chronic Obstructive Pulmonary Disorder (COPD) are characterized by chronic inflammation or elevation of the inflammatory mediators. While these disease states exhibit different pathologies, all have in common the loss of skeletal muscle mass and a deregulated skeletal muscle physiology. Pro-inflammatory cytokines are key contributors to chronic inflammation found in many of these diseases. This section of the review focuses on some of the known inflammatory disorders like COPD, Rheumatoid Arthritis (RA) and inflammatory myopathies that display skeletal muscle atrophy and also provides the reader an overview of the mediators of inflammation, their signaling pathways, and mechanisms of action. This article is part of a Special Issue entitled "Muscle Bone Interactions".

  5. A Dual-Role of Gu-4 in Suppressing HMGB1 Secretion and Blocking HMGB1 Pro-Inflammatory Activity during Inflammation

    PubMed Central

    Zhou, HuiTing; Ji, XueMei; Wu, Yun; Xuan, Ju; Qi, ZhiLin; Shen, Lei; Lan, Lei; Li, Qing; Yin, ZhiMin; Li, ZhongJun; Zhao, ZhiHui

    2014-01-01

    Background High mobility group box 1(HMGB1) was first recognized as a nuclear protein that increased the chromatin remodeling and regulates transcription of many genes. In recent years, HMGB1 has been identified as a critical “late” pro-inflammatory mediator due to its unique secretion pattern and lethal effects in sepsis. Therefore, preventing the active release and inhibiting the pro-inflammatory activity of HMGB1 become promising strategies for the treatment of sepsis. Here, we reported the therapeutic effects of Gu-4, a lactosyl derivative, on sepsis and the underlying molecular mechanisms. Methodology/Principal Findings In an experimental rat model of sepsis caused by cecal ligation and puncture (CLP), Gu-4 administration prominently attenuated lung injury and improved the survival of the septic animals, which was positively correlated with the decrease of the serum HMGB1 level. Using RAW264.7 macrophage cell line, we further showed that Gu-4 significantly suppressed the lipopolysaccharide (LPS)-induced release and cytoplasmic translocation of HMGB1. Moreover, Gu-4 not only dose-dependently attenuated recombinant human (rhHMGB1)-induced production of TNF-α, IL-6, and IL-1β in THP-1 cells, but also greatly inhibited the adhesion of rhHMGB1-challenged THP-1 cells to HUVECs. Analyses of flow cytometry demonstrated that Gu-4 could effectively reduce the activation of CD11b elicited by rhHMGB1. Western blot analyses revealed that Gu-4 treatment could partially block the rhHMGB1-induced activation of ERK and NF-κB signalings. Meanwhile, CD11b knockdown also obviously attenuated the rhHMGB1-induced phosphorylations of ERK and IKKα/β. Conclusions/Significance Taken together, our results suggest that Gu-4 possesses a therapeutic potential in the treatment of sepsis probably via inhibiting the LPS-induced release of HMGB1 from macrophages and via suppressing the pro-inflammatory activity of HMGB1. PMID:24603876

  6. 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

  7. 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.

  8. An acute vasculitis resembling polyarteritis nodosa.

    PubMed

    Unsal, E; Uğuz, A; Cevik, N

    1998-01-01

    Peripheral vascular disease are structural and functional abnormalities of the peripheral blood vessels that produce blood flow irregularities. The signs and symptoms relate either to ischemia or inflammation of the involved vessels, or to both. A previously healthy 4.5-year-old girl was referred to our hospital with bruises on fingers and toes. She had no history of environmental causes, including drug intake. Symptoms of abdominal pain, fever, and a swollen face preceded the symptoms of her extremities. On physical examination, her blood pressure, which could be obtained only on the things, was high. There were no pulses on the upper extremities or on either the a. dorsalis pedis or the a. tibialis anterior dextra. There was massive necrosis on fingers which led to dry gangrene. A rise in acute phase reactants accompanied the physical findings, and a segmental obstruction was found proximally to a. brachiales, and distally to a. radialis dextra and a. dorsalis pedis dextra on digital subtraction angiography (DSA). High-dose methylprednisolone, cyclophosphamide, salicylates and dipyridamole were given; as these medications did not relieve the symptoms, a thoracal sympathatectomy was performed. The peripheral circulation improved, but a demarcation zone developed on the fingertips, leading to amputation.

  9. 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

  10. Inflammation in diabetic kidney disease.

    PubMed

    García-García, Patricia M; Getino-Melián, María A; Domínguez-Pimentel, Virginia; Navarro-González, Juan F

    2014-08-15

    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

  11. 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

  12. 99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: immune therapies of type 1 diabetes: new opportunities based on the hygiene hypothesis.

    PubMed

    Chatenoud, L; You, S; Okada, H; Kuhn, C; Michaud, B; Bach, J-F

    2010-04-01

    Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting beta 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.

  13. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats

    PubMed Central

    Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

    2015-01-01

    The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg-1, intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg-1 decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3. PMID:26973766

  14. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats.

    PubMed

    Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

    2015-01-01

    The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg(-1), intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg(-1) decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3.

  15. 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

  16. 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

  17. 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

  18. 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. PMID:23281076

  19. 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

  20. Obesity and inflammation in children.

    PubMed

    Schwarzenberg, Sarah Jane; Sinaiko, Alan R

    2006-12-01

    Systemic inflammation is present in children and adults with obesity. Inflammation associated with obesity appears to be central to the development of insulin resistance and atherosclerosis and may be important in the pathogenesis of other comorbid conditions. Although generally considered an inert energy storage tissue, white adipose tissue is a metabolically active organ. It produces a number of inflammatory cytokines and acute-phase reactants. Inflammation associated with obesity declines after weight loss and with exercise. It may also be possible to modify obesity-associated inflammation with medications, reducing comorbidities without weight loss. The study of inflammation in the context of excessive adipose tissue is central to understanding obesity and modifying its impact on patients.

  1. Treating dyslipidemias: is inflammation the missing link?

    PubMed

    Papoutsidakis, Nikolaos; Deftereos, Spyridon; Giannopoulos, Georgios; Panagopoulou, Vasiliki; Manolis, Antonis S; Bouras, Georgios

    2014-01-01

    Low-grade chronic inflammation is now being held as an important process in the development of atherosclerosis, with new links between dyslipidemia and inflammation being constantly found. While most studies aim to discover inflammatory pathways leading from dyslipidemia to atherogenesis, there is evidence that inflammation can also act in reverse, altering lipid metabolism in unfavorable ways, possibly creating a vicious cycle of inflammationdyslipidemia- inflammation. This is highly relevant for the search of novel therapeutic targets. In this review, after a brief account of the inflammatory mechanisms leading from dyslipidemia to atherogenesis, we focus on what is currently known about the ways inflammation can impair lipid metabolism and whether anti-inflammatory therapies could have a role in dyslipidemia management.

  2. Overcoming immunosuppression in the melanoma microenvironment induced by chronic inflammation.

    PubMed

    Umansky, Viktor; Sevko, Alexandra

    2012-02-01

    Malignant melanoma is known by its rapid progression and poor response to currently applied treatments. Despite the well-documented melanoma immunogenicity, the results of immunotherapeutic clinical trials are not satisfactory. This poor antitumor reactivity is due to the development of chronic inflammation in the tumor microenvironment characterized by infiltrating leukocytes and soluble mediators, which lead to an immunosuppression associated with cancer progression. Using the ret transgenic mouse melanoma model that closely resembles human melanoma, we demonstrated increased levels of chronic inflammatory factors in skin tumors and metastatic lymph nodes, which correlated with tumor progression. Furthermore, Gr1(+)CD11b(+) myeloid-derived suppressor cells (MDSC), known to block tumor-reactive T cells, were enriched in melanoma lesions and showed an enhanced immunosuppressive capacity. This MDSC accumulation was associated with a strong TCR ζ-chain downregulation in T cells suggesting that the tumor inflammatory microenvironment supports MDSC recruitment and immunosuppressive activity. Indeed, upon administration of phosphodiesterase-5 inhibitor sildenafil or paclitaxel in non-cytotoxic doses, we observed reduced levels of chronic inflammatory mediators in association with decreased MDSC amounts and immunosuppressive function. This led to a partial restoration of ζ-chain expression in T cells and to a significantly increased survival of tumor-bearing mice. CD8 T-cell depletion resulted in an abrogation of beneficial outcome of both drugs, suggesting the involvement of MDSC and CD8 T cells in the observed therapeutic effects. Our data imply that inhibition of chronic inflammation in the tumor microenvironment should be applied in conjunction with melanoma immunotherapies to increase their efficacy. PMID:22120757

  3. Chronic Inflammation in Cancer Development

    PubMed Central

    Multhoff, Gabriele; Molls, Michael; Radons, Jürgen

    2012-01-01

    Chronic inflammatory mediators exert pleiotropic effects in the development of cancer. On the one hand, inflammation favors carcinogenesis, malignant transformation, tumor growth, invasion, and metastatic spread; on the other hand inflammation can stimulate immune effector mechanisms that might limit tumor growth. The link between cancer and inflammation depends on intrinsic and extrinsic pathways. Both pathways result in the activation of transcription factors such as NF-κB, STAT-3, and HIF-1 and in accumulation of tumorigenic factors in tumor and microenvironment. STAT-3 and NF-κB interact at multiple levels and thereby boost tumor-associated inflammation which can suppress anti-tumor immune responses. These factors also promote tumor growth, progression, and metastatic spread. IL-1, IL-6, TNF, and PGHS-2 are key mediators of an inflammatory milieu by modulating the expression of tumor-promoting factors. In this review we concentrate on the crucial role of pro-inflammatory mediators in inflammation-driven carcinogenesis and outline molecular mechanisms of IL-1 signaling in tumors. In addition, we elucidate the dual roles of stress proteins as danger signals in the development of anti-cancer immunity and anti-apoptotic functions. PMID:22566887

  4. 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

  5. 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 and animal experimental models. The applications of probiotics considered are systemic immune-modulation, the metabolic syndrome, liver injury, inflammatory bowel disease, colorectal cancer and radiation-induced enteritis. When the major genomic differences between different types of probiotics are taken into account, it is to be expected that the human body can respond differently to the different species and strains of probiotics. This fact is often neglected in discussions of the outcome of clinical trials with probiotics. PMID:22254115

  6. Cognitive Resemblance and Citation Relations in Chemical Engineering Publications.

    ERIC Educational Resources Information Center

    Peters, H. P. F.; And Others

    1995-01-01

    Describes an empirical study that measured word-profile similarities between citing and cited publications in the chemical engineering field. Highlights include cognitive resemblance and bibliographic coupling; data collection techniques; analysis of word-profile similarity; bibliographic coupled publications; mapping of cognitive resemblance; and…

  7. The role of platelets in inflammation.

    PubMed

    Thomas, Mark R; Storey, Robert F

    2015-08-31

    There is growing recognition of the critical role of platelets in inflammation and immune responses. Recent studies have indicated that antiplatelet medications may reduce mortality from infections and sepsis, which suggests possible clinical relevance of modifying platelet responses to inflammation. Platelets release numerous inflammatory mediators that have no known role in haemostasis. Many of these mediators modify leukocyte and endothelial responses to a range of different inflammatory stimuli. Additionally, platelets form aggregates with leukocytes and form bridges between leukocytes and endothelium, largely mediated by platelet P-selectin. Through their interactions with monocytes, neutrophils, lymphocytes and the endothelium, platelets are therefore important coordinators of inflammation and both innate and adaptive immune responses.

  8. Frailty, Inflammation and Immunosenescence.

    PubMed

    Fulop, Tamas; McElhaney, Janet; Pawelec, Graham; Cohen, Alan A; Morais, José A; Dupuis, Gilles; Baehl, Sarra; Camous, Xavier; Witkowski, Jacek M; Larbi, Anis

    2015-01-01

    Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state. PMID:26301977

  9. Sleep Loss and Inflammation

    PubMed Central

    Simpson, Norah S.; Meier-Ewert, Hans K.; Haack, Monika

    2012-01-01

    Controlled, experimental studies on the effects of acute sleep loss in humans have shown that mediators of inflammation are altered by sleep loss. Elevations in these mediators have been found to occur in healthy, rigorously screened individuals undergoing experimental vigils of more than 24 hours, and have also been seen in response to various durations of sleep restricted to between 25 and 50% of a normal 8 hour sleep amount. While these altered profiles represent small changes, such sub-clinical shifts in basal inflammatory cytokines are known to be associated with the future development of metabolic syndrome disease in healthy, asymptomatic individuals. Although the mechanism of this altered inflammatory status in humans undergoing experimental sleep loss is unknown, it is likely that autonomic activation and metabolic changes play key roles. PMID:21112025

  10. Macrophages in Vascular Inflammation: Origins and Functions.

    PubMed

    Decano, Julius L; Mattson, Peter C; Aikawa, Masanori

    2016-06-01

    Macrophages influence various processes of cardiovascular inflammation. Whether they are of embryonic or post-natal hematopoietic origin, their balance in differential activation may direct the course of inflammation. Accelerated macrophage activation and accumulation through a pro-inflammatory signaling pathway may result in extensive tissue damage, adverse repair, and worsened clinical outcomes. Attenuation of such a mechanism and/or promotion of the anti-inflammatory macrophage activation may lead to early resolution of inflammation. Elucidating multiple novel mechanisms of monocyte and macrophage activation leads to a better understanding of their roles in vascular inflammation. In turn, this begets better therapeutic target identification and biomarker discovery. Combined with increasingly sensitive and specific imaging techniques, we continue to push back early detection and monitoring to provide us with a greater window for disease modification. The potential success of cytokine-targeted therapy will be solid proof of the inflammatory hypothesis of atherothrombosis. PMID:27125207

  11. Neurotrauma and Inflammation: CNS and PNS Responses

    PubMed Central

    Mietto, Bruno Siqueira; Mostacada, Klauss; Martinez, Ana Maria Blanco

    2015-01-01

    Traumatic injury to the central nervous system (CNS) or the peripheral nervous system (PNS) triggers a cascade of events which culminate in a robust inflammatory reaction. The role played by inflammation in the course of degeneration and regeneration is not completely elucidated. While, in peripheral nerves, the inflammatory response is assumed to be essential for normal progression of Wallerian degeneration and regeneration, CNS trauma inflammation is often associated with poor recovery. In this review, we discuss key mechanisms that trigger the inflammatory reaction after nervous system trauma, emphasizing how inflammations in both CNS and PNS differ from each other, in terms of magnitude, cell types involved, and effector molecules. Knowledge of the precise mechanisms that elicit and maintain inflammation after CNS and PNS tissue trauma and their effect on axon degeneration and regeneration is crucial for the identification of possible pharmacological drugs that can positively affect the tissue regenerative capacity. PMID:25918475

  12. Focus issue: understanding mechanisms of inflammation.

    PubMed

    Foley, John F

    2013-01-15

    This Focus Issue of Science Signaling, which complements the Science Special Issue on Inflammation, includes research that reveals regulators of a receptor implicated in an inflammatory bowel disease, as well as the contribution of a matrix metalloproteinase to skin inflammation. Perspectives discuss the role of proinflammatory cytokines in brain inflammatory disorders and the regulation of multiple types of cell death in tissues in response to proinflammatory factors. Together with content from the Science Signaling Archives, these articles underline the importance of understanding the basis of inflammatory responses that can both protect and harm the host. PMID:23322902

  13. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  14. Genetic aspects of inflammation and cancer.

    PubMed

    Hold, Georgina L; El-Omar, Emad M

    2008-03-01

    Chronic inflammation is involved in the pathogenesis of most common cancers. The aetiology of the inflammation is varied and includes microbial, chemical and physical agents. The chronically inflamed milieu is awash with pro-inflammatory cytokines and is characterized by the activation of signalling pathways that cross-talk between inflammation and carcinogenesis. Many of the factors involved in chronic inflammation play a dual role in the process, promoting neoplastic progression but also facilitating cancer prevention. A comprehensive understanding of the molecular and cellular inflammatory mechanisms involved is vital for developing preventive and therapeutic strategies against cancer. The purpose of the present review is to evaluate the mechanistic pathways that underlie chronic inflammation and cancer with particular emphasis on the role of host genetic factors that increase the risk of carcinogenesis.

  15. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird".

    PubMed

    de Herder, Wouter W

    2016-04-01

    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology. PMID:26812692

  16. Pareidolia in Neuroendocrinology: A Pituitary Macroadenoma Resembling "Big Bird".

    PubMed

    de Herder, Wouter W

    2016-04-01

    The MRI picture of a pituitary macroadenoma with supra- and perisellar expansion resembled a famous character from a children's television series demonstrating that pareidolia is also observed in neuro-endocrinology and -radiology.

  17. Sirtuins Link Inflammation and Metabolism.

    PubMed

    Vachharajani, Vidula T; Liu, Tiefu; Wang, Xianfeng; Hoth, Jason J; Yoza, Barbara K; McCall, Charles E

    2016-01-01

    Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1-7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to "defend and mend" against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to "defend" against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to "mend," leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis. PMID:26904696

  18. Sirtuins Link Inflammation and Metabolism

    PubMed Central

    Vachharajani, Vidula T.; Liu, Tiefu; Wang, Xianfeng; Hoth, Jason J.; Yoza, Barbara K.; McCall, Charles E.

    2016-01-01

    Sirtuins (SIRT), first discovered in yeast as NAD+ dependent epigenetic and metabolic regulators, have comparable activities in human physiology and disease. Mounting evidence supports that the seven-member mammalian sirtuin family (SIRT1–7) guard homeostasis by sensing bioenergy needs and responding by making alterations in the cell nutrients. Sirtuins play a critical role in restoring homeostasis during stress responses. Inflammation is designed to “defend and mend” against the invading organisms. Emerging evidence supports that metabolism and bioenergy reprogramming direct the sequential course of inflammation; failure of homeostasis retrieval results in many chronic and acute inflammatory diseases. Anabolic glycolysis quickly induced (compared to oxidative phosphorylation) for ROS and ATP generation is needed for immune activation to “defend” against invading microorganisms. Lipolysis/fatty acid oxidation, essential for cellular protection/hibernation and cell survival in order to “mend,” leads to immune repression. Acute/chronic inflammations are linked to altered glycolysis and fatty acid oxidation, at least in part, by NAD+ dependent function of sirtuins. Therapeutically targeting sirtuins may provide a new class of inflammation and immune regulators. This review discusses how sirtuins integrate metabolism, bioenergetics, and immunity during inflammation and how sirtuin-directed treatment improves outcome in chronic inflammatory diseases and in the extreme stress response of sepsis. PMID:26904696

  19. Bioactive Egg Components and Inflammation

    PubMed Central

    Andersen, Catherine J.

    2015-01-01

    Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk. PMID:26389951

  20. Leptin and Inflammation

    PubMed Central

    Iikuni, Noriko; Lam, Queenie Lai Kwan; Lu, Liwei; Matarese, Giuseppe; La Cava, Antonio

    2009-01-01

    The past few years of research on leptin have provided important information on the link between metabolism and immune homeostasis. Adipocytes influence not only the endocrine system but also the immune response through several cytokine-like mediators known as adipokines, which include leptin. It is widely accepted that leptin can directly link nutritional status and pro-inflammatory T helper 1 immune responses, and that a decrease of leptin plasma concentration during food deprivation can lead to an impaired immune function. Additionally, several studies have implicated leptin in the pathogenesis of chronic inflammation, and the elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, type II diabetes, or degenerative disease including autoimmunity and cancer. Conversely, reduced levels of leptin such as those found in malnourished individuals have been linked to increased risk of infection and reduced cell-mediated immune responses. We discuss here the functional influences of leptin in the physiopathology of inflammation, and the effects of leptin in the modulation of such responses. PMID:20198122

  1. Role of hypoxia-inducible factor 1{alpha} in modulating cobalt-induced lung inflammation.

    PubMed

    Saini, Yogesh; Kim, Kyung Y; Lewandowski, Ryan; Bramble, Lori A; Harkema, Jack R; Lapres, John J

    2010-02-01

    Hypoxia plays an important role in development, cellular homeostasis, and pathological conditions, such as cancer and stroke. There is also growing evidence that hypoxia is an important modulator of the inflammatory process. Hypoxia-inducible factors (HIFs) are a family of proteins that regulate the cellular response to oxygen deficit, and loss of HIFs impairs inflammatory cell function. There is little known, however, about the role of epithelial-derived HIF signaling in modulating inflammation. Cobalt is capable of eliciting an allergic response and promoting HIF signaling. To characterize the inflammatory function of epithelial-derived HIF in response to inhaled cobalt, a conditional lung-specific HIF1alpha, the most ubiquitously expressed HIF, deletion mouse, was created. Control mice showed classic signs of metal-induced injury following cobalt exposure, including fibrosis and neutrophil infiltration. In contrast, HIF1alpha-deficient mice displayed a Th2 response that resembled asthma, including increased eosinophilic infiltration, mucus cell metaplasia, and chitinase-like protein expression. The results suggest that epithelial-derived HIF signaling has a critical role in establishing a tissue's inflammatory response, and compromised HIF1alpha signaling biases the tissue towards a Th2-mediated reaction. PMID:19915160

  2. Inflammatory and toxic myopathy.

    PubMed

    Teener, James W

    2012-11-01

    Although muscle diseases are relatively rare, several treatable myopathies must be recognized by the clinician to maximize the possibility of restoring strength in affected patients. The inflammatory myopathies, including polymyositis, dermatomyositis, inflammatory necrotizing myopathy, and myositis in association with mixed connective tissue disease, typically respond well to immunosuppressive treatment. Inclusion body myositis, a myopathy that has features of both inflammation and primary degeneration, may not be treatable at this time, but treatments are actively being sought. Muscle dysfunction caused by toxins must also be recognized because removal of the offending toxin usually results in restoration of normal muscle function. Important muscle toxins include cholesterol-lowering medications, colchicine, zidovudine, corticosteroids, emetine, and ethanol.

  3. The effect of maternal Inflammation on foetal programming of metabolic disease.

    PubMed

    Ingvorsen, C; Brix, S; Ozanne, S E; Hellgren, L I

    2015-08-01

    Maternal obesity during pregnancy increases the child's risk of developing obesity and obesity-related diseases later in life. Key components in foetal programming of metabolic risk remain to be identified; however, chronic low-grade inflammation associated with obesity might be responsible for metabolic imprinting in the offspring. We have therefore surveyed the literature to evaluate the role of maternal obesity-induced inflammation in foetal programming of obesity and related diseases. The literature on this topic is limited, so this review also includes animal models where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS). An LPS challenge results in an immunological response that resembles the obesity-induced immune profile, although LPS injections provoke a stronger response than the subclinical obesity-associated response. Maternal LPS or cytokine exposures result in increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. The cytokine levels might be specifically important for the metabolic imprinting, as cytokines are both transferable from maternal to foetal circulation and have the capability to modulate placental nutrient transfer. However, the immune response associated with obesity is moderate and therefore potentially weakened by the pregnancy-driven immune modulation, dominated by anti-inflammatory Treg and Th2 cells. We know from other low-grade inflammatory diseases, such as rheumatoid arthritis, that pregnancy can improve disease state. If pregnancy is also capable of suppressing the obesity-associated inflammation, the immunological markers might be less likely to affect metabolic programming in the developing foetus than otherwise implied.

  4. Inflammation: therapeutic targets for diabetic neuropathy.

    PubMed

    Zhou, Jiyin; Zhou, Shiwen

    2014-02-01

    There are still no approved treatments for the prevention or of cure of diabetic neuropathy, and only symptomatic pain therapies of variable efficacy are available. Inflammation is a cardinal pathogenic mechanism of diabetic neuropathy. The relationships between inflammation and the development of diabetic neuropathy involve complex molecular networks and processes. Herein, we review the key inflammatory molecules (inflammatory cytokines, adhesion molecules, chemokines) and pathways (nuclear factor kappa B, JUN N-terminal kinase) implicated in the development and progression of diabetic neuropathy. Advances in the understanding of the roles of these key inflammatory molecules and pathways in diabetic neuropathy will facilitate the discovery of the potential of anti-inflammatory approaches for the inhibition of the development of neuropathy. Specifically, many anti-inflammatory drugs significantly inhibit the development of different aspects of diabetic neuropathy in animal models and clinical trials.

  5. Role of inflammation in the aging bones.

    PubMed

    Abdelmagid, Samir M; Barbe, Mary F; Safadi, Fayez F

    2015-02-15

    Chronic inflammation in aging is characterized by increased inflammatory cytokines, bone loss, decreased adaptation, and defective tissue repair in response to injury. Aging leads to inherent changes in mesenchymal stem cell (MSC) differentiation, resulting in impaired osteoblastogenesis. Also, the pro-inflammatory cytokines increase with aging, leading to enhanced myelopoiesis and osteoclastogenesis. Bone marrow macrophages (BMMs) play pivotal roles in osteoblast differentiation, the maintenance of hematopoietic stem cells (HSCs), and subsequent bone repair. However, during aging, little is known about the role of macrophages in the differentiation and function of MSC and HSC. Aged mammals have higher circulating pro-inflammatory cytokines than young adults, supporting the hypothesis of increased inflammation with aging. This review will aid in the understanding of the potential role(s) of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages in differentiation and function of osteoblasts and osteoclasts in relation to aging.

  6. The Immune System in Tissue Environments Regaining Homeostasis after Injury: Is "Inflammation" Always Inflammation?

    PubMed

    Kulkarni, Onkar P; Lichtnekert, Julia; Anders, Hans-Joachim; Mulay, Shrikant R

    2016-01-01

    Inflammation is a response to infections or tissue injuries. Inflammation was once defined by clinical signs, later by the presence of leukocytes, and nowadays by expression of "proinflammatory" cytokines and chemokines. But leukocytes and cytokines often have rather anti-inflammatory, proregenerative, and homeostatic effects. Is there a need to redefine "inflammation"? In this review, we discuss the functions of "inflammatory" mediators/regulators of the innate immune system that determine tissue environments to fulfill the need of the tissue while regaining homeostasis after injury. PMID:27597803

  7. Osteoprotegerin and inflammation.

    PubMed

    Saidenberg Kermanac'h, N; Bessis, Natacha; Cohen-Solal, M; De Vernejoul, M C; Boissier, Marie-Christophe

    2002-01-01

    RANK, RANKL, and OPG have well established regulatory effects on bone metabolism. RANK is expressed at very high levels on osteoclastic precursors and on mature osteoclasts, and is required for differentiation and activation of the osteoclast. The ligand, RANKL binds to its receptor RANK to induce bone resorption. RANKL is a transmembrane protein expressed in various cells type and particularly on osteoblast and activated T cells. RANKL can be cleaved and the soluble form is active. Osteoprotegerin decoy receptor (OPG), a member of the TNF receptor family expressed by osteoblasts, strongly inhibits bone resorption by binding with high affinity to its ligand RANKL, thereby preventing RANKL from engaging its receptor RANK. This system is regulated by the calciotropic hormones. Conversely, the effects of RANKL, RANK, and OPG on inflammatory processes, most notably on the bone resorption associated with inflammation, remain to be defined. The RANK system seems to play a major role in modulating the immune system. Activated T cells express RANKL messenger RNA, and knock-out mice for RANKL acquire severe immunological abnormalities and osteopetrosis. RANKL secretion by activated T cells can induce osteoclastogenesis. These mechanisms are enhanced by cytokines such as TNF-alpha, IL-1, and IL-17, which promote both inflammation and bone resorption. Conversely, this system is blocked by OPG, IL-4, and IL-10, which inhibit both inflammation and osteoclastogenesis. These data may explain part of the abnormal phenomena in diseases such as rheumatoid arthritis characterized by both inflammation and destruction. Activated T cells within the rheumatoid synovium express RANKL. Synovial cells are capable of differentiating to osteoclast-like cells under some conditions, including culturing with M-CSF and RANKL. This suggests that the bone erosion seen in rheumatoid arthritis may result from RANKL/RANK system activation by activated T cells. This opens up the possibility that OPG

  8. Inflammation, Sanitation, and Consternation

    PubMed Central

    Raison, Charles L.; Lowry, Christopher A.; Rook, Graham A. W.

    2013-01-01

    Context Inflammation is increasingly recognized as contributing to the pathogenesis of major depressive disorder (MDD), even in individuals who are otherwise medically healthy. Most studies in search of sources for this increased inflammation have focused on factors such as psychosocial stress and obesity that are known to activate inflammatory processes and increase the risk for depression. However, MDD may be so prevalent in the modern world not just because proinflammatory factors are widespread, but also because we have lost contact with previously available sources of anti-inflammatory, immunoregulatory signaling. Objective To examine evidence that disruptions in co-evolved relationships with a variety of tolerogenic microorganisms that were previously ubiquitous in soil, food, and the gut, but that are largely missing from industrialized societies, may contribute to increasing rates of MDD in the modern world. Data Sources Relevant studies were identified using PubMed and Ovid MEDLINE. Study Selection Included were laboratory animal and human studies relevant to immune functioning, the hygiene hypothesis, and major depressive disorder identified via PubMed and Ovid MEDLINE searches. Data Extraction Studies were reviewed by all authors, and data considered to be potentially relevant to the contribution of hygiene-related immune variables to major depressive disorder were extracted. Data Synthesis Significant data suggest that a variety of microorganisms (frequently referred to as the “old friends”) were tasked by coevolutionary processes with training the human immune system to tolerate a wide array of nonthreatening but potentially proinflammatory stimuli. Lacking such immune training, vulnerable individuals in the modern world are at significantly increased risk of mounting inappropriate inflammatory attacks on harmless environmental antigens (leading to asthma), benign food contents and commensals in the gut (leading to inflammatory bowel disease), or

  9. Intentions vs. resemblance: understanding pictures in typical development and autism.

    PubMed

    Hartley, Calum; Allen, Melissa L

    2014-04-01

    Research has debated whether children reflect on artists' intentions when comprehending pictures, or instead derive meaning entirely from resemblance. We explore these hypotheses by comparing how typically developing toddlers and low-functioning children with autism (a population impaired in intentional reasoning) interpret abstract pictures. In Experiment 1, both groups mapped familiar object names onto abstract pictures, however, they related the same representations to different 3-D referents. Toddlers linked abstract pictures with intended referents they did not resemble, while children with autism mapped picture-referent relations based on resemblance. Experiment 2 showed that toddlers do not rely upon linguistic cues to determine intended referential relations. Experiment 3 confirmed that the responding of children with autism was not due to perseveration or associative word learning, and also provided independent evidence of their intention-reading difficulties. We argue that typically developing children derive meaning from the social-communicative intentions underlying pictures when resemblance is an inadequate cue to meaning. By contrast, children with autism do not reflect on artists' intentions and simply relate pictures to whatever they happen to resemble.

  10. A Distinct Fatty Acid Profile Underlies the Reduced Inflammatory State of Metabolically Healthy Obese Individuals

    PubMed Central

    Badoud, Flavia; Stephenson, Susan; Badawi, Alaa; Buchholz, Andrea; Mutch, David M.

    2014-01-01

    Background Obesity is associated with numerous health complications; however, a subgroup of obese individuals (termed the metabolically healthy obese or MHO) appear to have lower risk for complications such as type 2 diabetes and cardiovascular disease. Emerging evidence suggests that MHO individuals have reduced inflammation compared to their metabolically unhealthy obese (MUO) counterparts. As it is recognized that fatty acids (FAs) have a strong relationship with inflammation, the current study aimed to uncover if the reduced inflammation observed in MHO individuals is mirrored by a more favourable FA profile. Methods Fasted serum samples were collected from lean healthy (LH), MHO, and MUO participants (n = 10/group) recruited from the Diabetes Risk Assessment study. A panel of pro- and anti-inflammatory markers were measured by immunoassay. Total serum FA profiling, as well as the FA composition of circulating phospholipids (PL) and triglycerides (TG), was measured by gas chromatography. ANOVA and Mann-Whitney-Wilcoxon tests were used to assess statistical significance between the groups (P<0.05). Results MHO and MUO individuals had similar BMI and body fat %; however, lipid parameters in MHO individuals more closely resembled that of LH individuals. MHO individuals had circulating levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) similar to LH individuals, while levels of platelet derived growth factor-ββ (PDGF-ββ) were intermediate to that of LH and MUO individuals. FA profiling analysis combined with discriminant analysis modelling highlighted a panel of nine FAs (consisting of three saturated, three monounsaturated, and three polyunsaturated FAs) in PL and TG fractions that distinguished the three groups. Specifically, saturated FA (myristic and stearic acids) levels in MHO individuals resembled that of LH individuals. Conclusion Our results suggest that the reduced inflammatory state of MHO individuals compared to MUO

  11. Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons

    NASA Astrophysics Data System (ADS)

    Neumann, Simona; Doubell, Tim P.; Leslie, Tabi; Woolf, Clifford J.

    1996-11-01

    PAIN is normally evoked only by stimuli that are sufficiently intense to activate high-threshold Aδ and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of Aδ and C fibres at the site of inflammation1. It also increases the excitability of spinal cord neurons2,3, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold Aβ fibres. This central sensitization has been attributed to the enhanced activity of C fibres4, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P5-7. Here we show that inflammation results in Aβ fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. Aβ fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli.

  12. Pain related inflammation analysis using infrared images

    NASA Astrophysics Data System (ADS)

    Bhowmik, Mrinal Kanti; Bardhan, Shawli; Das, Kakali; Bhattacharjee, Debotosh; Nath, Satyabrata

    2016-05-01

    Medical Infrared Thermography (MIT) offers a potential non-invasive, non-contact and radiation free imaging modality for assessment of abnormal inflammation having pain in the human body. The assessment of inflammation mainly depends on the emission of heat from the skin surface. Arthritis is a disease of joint damage that generates inflammation in one or more anatomical joints of the body. Osteoarthritis (OA) is the most frequent appearing form of arthritis, and rheumatoid arthritis (RA) is the most threatening form of them. In this study, the inflammatory analysis has been performed on the infrared images of patients suffering from RA and OA. For the analysis, a dataset of 30 bilateral knee thermograms has been captured from the patient of RA and OA by following a thermogram acquisition standard. The thermograms are pre-processed, and areas of interest are extracted for further processing. The investigation of the spread of inflammation is performed along with the statistical analysis of the pre-processed thermograms. The objectives of the study include: i) Generation of a novel thermogram acquisition standard for inflammatory pain disease ii) Analysis of the spread of the inflammation related to RA and OA using K-means clustering. iii) First and second order statistical analysis of pre-processed thermograms. The conclusion reflects that, in most of the cases, RA oriented inflammation affects bilateral knees whereas inflammation related to OA present in the unilateral knee. Also due to the spread of inflammation in OA, contralateral asymmetries are detected through the statistical analysis.

  13. [Adipose tissue inflammation and atherosclerosis].

    PubMed

    Shwarts, V

    2009-01-01

    Adipose tissue is an endocrine organ secreting more than 30 various adipokines which regulate wide spectrum of metabolic and immune processes. Obesity is associated with development of adipose tissue inflammation. This inflammation is characterized by infiltration with macrophages, alterations of adipokine secretion, development of insulin resistance. All these factors promote atherosclerosis. Inflammation of perivascular adipose tissue is especially important. Adipokines damage vascular endothelium via paracrine pathway. Cytokines released by macrophages as well as changes of adipokine secretion lead to endothelial dysfunction - the first stage of atherogenesis. Besides specific action curative factors used in obesity, metabolic syndrome, and diabetes mellitus also produce anti-inflammatory effect and thus diminish risk factors of cardiovascular diseases, rate of their development, and alleviate manifestations of atherosclerosis. Inflammation of adipose tissue is a connecting link between obesity and atherosclerosis. This review contains an outline of roles of various major adipokines in development of atherosclerosis as well as synopsis of anti-inflammatory and antiatherogenic effects of glytazones , metformin, rimonabant, statins, and of lowering of body weight.

  14. Effect of Pregnancy Serum on Experimental Inflammation

    PubMed Central

    Persellin, R. H.; Vance, S. E.; Peery, A.

    1974-01-01

    Experimental inflammation induced in the rat by injection of carrageenin was suppressed by prior administration of pooled serum obtained from pregnant human females. Inflammatory oedema in the rat hind paw measured by a plethysmograph was inhibited 81% by 10 ml of pregnancy serum pool and the effect was dose related. Non-pregnant female serum was inhibitory to a lesser degree and no anti-inflammatory action was detected using cord serum. Although adrenal corticosteroid hormones could modify this inflammatory model, their presence in the serum pools could not account for the effects observed. Since carrageenin is sequestered within phagolysosomes and provokes release of their inflammation-inducing contents, it is suggested that the protective effect of pregnancy serum on carrageenin inflammation is mediated via lysosomal stabilization. PMID:4835795

  15. Inflammation: maladies, models, mechanisms and molecules.

    PubMed

    Stewart, A G; Beart, P M

    2016-02-01

    The continued focus of attention on the diversity of mechanisms underpinning inflammation has improved our understanding of the potential to target specific pathways in the inflammatory network to achieve meaningful therapeutic gains. In this themed issue of the British Journal of Pharmacology our scope was deliberately broad, ranging across both acute and chronic disease in various organs. Pro- and anti-inflammatory mechanisms receive attention as does the phenotype of macrophages. Whilst the manifestations of neuro-inflammation are less obvious than those in peripheral tissues, central innate and adaptive immunity in brain and the M1/M2 phenotypes of microglia are topics of special interest. The contributions to the inflammatory milieu of cytokines, chemokines and associated signalling cascades are considered. Overall, the coverage herein advances the basic science underpinning our understanding of inflammation and emphasizes its importance in different pathologies.

  16. Inflammation in Sleep Apnea: An Update

    PubMed Central

    Unnikrishnan, Dileep; Jun, Jonathan; Polotsky, Vsevolod

    2014-01-01

    Obstructive sleep apnea (OSA) is a common disorder associated with cardiovascular disease (CVD). One theory to explain this relationship proposes that OSA can induce systemic inflammation, thereby inducing CVD. This theory is based on the premise that obesity is a pro-inflammatory state, and that physiological derangements during sleep in subjects with OSA further aggravate inflammation. In support of this theory, some clinical studies have shown elevated inflammatory biomarkers in OSA subjects, or improvement in these markers following treatment of OSA. However, the data are inconsistent and often confounded by the effects of comorbid obesity. Animal models of OSA have been developed, which involve exposure of rodents or cells to intermittent hypoxia, a hallmark feature of OSA. Several of these experiments demonstrate that intermittent hypoxia can stimulate inflammatory pathways and lead to cardiovascular or metabolic pathology. In this review, we review relationships between OSA and inflammation, with particular attention to studies published within the last year. PMID:25502450

  17. Multiple Roles of Peroxiredoxins in Inflammation

    PubMed Central

    Knoops, Bernard; Argyropoulou, Vasiliki; Becker, Sarah; Ferté, Laura; Kuznetsova, Oksana

    2016-01-01

    Inflammation is a pathophysiological response to infection or tissue damage during which high levels of reactive oxygen and nitrogen species are produced by phagocytes to kill microorganisms. Reactive oxygen and nitrogen species serve also in the complex regulation of inflammatory processes. Recently, it has been proposed that peroxiredoxins may play key roles in innate immunity and inflammation. Indeed, peroxiredoxins are evolutionarily conserved peroxidases able to reduce, with high rate constants, hydrogen peroxide, alkyl hydroperoxides and peroxynitrite which are generated during inflammation. In this minireview, we point out different possible roles of peroxiredoxins during inflammatory processes such as cytoprotective enzymes against oxidative stress, modulators of redox signaling, and extracellular pathogen- or damage-associated molecular patterns. A better understanding of peroxiredoxin functions in inflammation could lead to the discovery of new therapeutic targets. PMID:26813661

  18. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

    PubMed

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J

    2015-01-01

    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris. PMID:25782705

  19. Allergic Contact Dermatitis to Benzoyl Peroxide Resembling Impetigo.

    PubMed

    Kim, Changhyun; Craiglow, Brittany G; Watsky, Kalman L; Antaya, Richard J

    2015-01-01

    A 17-year-old boy presented with recurring severe dermatitis of the face of 5-months duration that resembled impetigo. He had been treated with several courses of antibiotics without improvement. Biopsy showed changes consistent with allergic contact dermatitis and patch testing later revealed sensitization to benzoyl peroxide, which the patient had been using for the treatment of acne vulgaris.

  20. Factor V Leiden and Inflammation

    PubMed Central

    Perez-Pujol, Silvia; Aras, Omer; Escolar, Gines

    2012-01-01

    Factor V Leiden, is a variant of human factor V (FV), also known as proaccelerin, which leads to a hypercoagulable state. Along these years, factor V Leiden (FVL) has been studied from the pathophysiologic point of view, and research has been focused on finding clinical approaches for the management of the FVL associated to a trombophilic state. Less attention has been paid about the possible role of FVL in inflammatory conditions known to be present in different disorders such as uremia, cirrhosis, liver transplantation, depression as well as sepsis, infection or, inflammatory bowel disease (IBD). Whether platelet FVL will increase the activation of coagulation and/or in which proportion is able to determine the final outcome in the previously mentioned inflammatory conditions is a subject that remains uncertain. This paper will review the association of FVL with inflammation. Specifically, it will analyze the important role of the endothelium and the contribution of other inflammatory components involved at both the immune and vascular levels. This paper will also try to emphasize the importance of being a FVL carrier in associations to diseases where a chronic inflammation occurs, and how this condition may be determinant in the progression and outcome of a specific clinic situation. PMID:22666576

  1. Inflammation: a trigger for acute coronary syndrome.

    PubMed

    Sager, Hendrik B; Nahrendorf, Matthias

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis' most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes. PMID:27273431

  2. Resolution of Inflammation: What Controls Its Onset?

    PubMed

    Sugimoto, Michelle A; Sousa, Lirlândia P; Pinho, Vanessa; Perretti, Mauro; Teixeira, Mauro M

    2016-01-01

    An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as "resolution pharmacology."

  3. Meibomian glands and ocular surface inflammation.

    PubMed

    Suzuki, Tomo; Teramukai, Satoshi; Kinoshita, Shigeru

    2015-04-01

    The purpose of this review was to systematically analyze publications related to the role of meibomian gland disease in ocular surface inflammation, with special reference to meibomitis as an inflammatory form of meibomian gland dysfunction (MGD). Meibomian gland inflammation is often present with the ocular surface inflammation in conditions such as blepharokeratoconjunctivitis, ocular rosacea, and phlyctenular keratitis, but its contribution is often overlooked, especially in younger subjects. This can result in misdiagnosis, mistreatment, and, sometimes, severe visual impairment. We identified a related disease entity, seen predominantly in young patients, of ocular surface inflammation associated with meibomitis, which we termed meibomitis-related keratoconjunctivitis. Its specific clinical features are similar to those observed in the above-mentioned diseases, and the inflammatory form of MGD was found to be closely involved in the ocular surface inflammation seen in those four diseases, based on our statistical evaluation. The diagnosis and management of meibomitis, an inflammatory form of MGD, is vital for the successful treatment of the induced ocular surface inflammation. We propose that the ocular surface and the adnexal meibomian glands should be considered as one unit, i.e., the "meibomian gland and ocular surface" (MOS), when encountered in the clinical setting.

  4. Resolution of Inflammation: What Controls Its Onset?

    PubMed Central

    Sugimoto, Michelle A.; Sousa, Lirlândia P.; Pinho, Vanessa; Perretti, Mauro; Teixeira, Mauro M.

    2016-01-01

    An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as “resolution pharmacology.” PMID:27199985

  5. Resolution of Inflammation: What Controls Its Onset?

    PubMed

    Sugimoto, Michelle A; Sousa, Lirlândia P; Pinho, Vanessa; Perretti, Mauro; Teixeira, Mauro M

    2016-01-01

    An effective resolution program may be able to prevent the progression from non-resolving acute inflammation to persistent chronic inflammation. It has now become evident that coordinated resolution programs initiate shortly after inflammatory responses begin. In this context, several mechanisms provide the fine-tuning of inflammation and create a favorable environment for the resolution phase to take place and for homeostasis to return. In this review, we focus on the events required for an effective transition from the proinflammatory phase to the onset and establishment of resolution. We suggest that several mediators that promote the inflammatory phase of inflammation can simultaneously initiate a program for active resolution. Indeed, several events enact a decrease in the local chemokine concentration, a reduction which is essential to inhibit further infiltration of neutrophils into the tissue. Interestingly, although neutrophils are cells that characteristically participate in the active phase of inflammation, they also contribute to the onset of resolution. Further understanding of the molecular mechanisms that initiate resolution may be instrumental to develop pro-resolution strategies to treat complex chronic inflammatory diseases, in humans. The efforts to develop strategies based on resolution of inflammation have shaped a new area of pharmacology referred to as "resolution pharmacology." PMID:27199985

  6. Meibomian glands and ocular surface inflammation.

    PubMed

    Suzuki, Tomo; Teramukai, Satoshi; Kinoshita, Shigeru

    2015-04-01

    The purpose of this review was to systematically analyze publications related to the role of meibomian gland disease in ocular surface inflammation, with special reference to meibomitis as an inflammatory form of meibomian gland dysfunction (MGD). Meibomian gland inflammation is often present with the ocular surface inflammation in conditions such as blepharokeratoconjunctivitis, ocular rosacea, and phlyctenular keratitis, but its contribution is often overlooked, especially in younger subjects. This can result in misdiagnosis, mistreatment, and, sometimes, severe visual impairment. We identified a related disease entity, seen predominantly in young patients, of ocular surface inflammation associated with meibomitis, which we termed meibomitis-related keratoconjunctivitis. Its specific clinical features are similar to those observed in the above-mentioned diseases, and the inflammatory form of MGD was found to be closely involved in the ocular surface inflammation seen in those four diseases, based on our statistical evaluation. The diagnosis and management of meibomitis, an inflammatory form of MGD, is vital for the successful treatment of the induced ocular surface inflammation. We propose that the ocular surface and the adnexal meibomian glands should be considered as one unit, i.e., the "meibomian gland and ocular surface" (MOS), when encountered in the clinical setting. PMID:25881997

  7. The circadian clock regulates inflammatory arthritis

    PubMed Central

    Hand, Laura E.; Hopwood, Thomas W.; Dickson, Suzanna H.; Walker, Amy L.; Loudon, Andrew S. I.; Ray, David W.; Bechtold, David A.; Gibbs, Julie E.

    2016-01-01

    There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins cryptochrome (CRY) 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRY activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.—Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray, D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis. PMID:27488122

  8. Microbes, intestinal inflammation and probiotics.

    PubMed

    Khan, Mohammad W; Kale, Amod A; Bere, Praveen; Vajjala, Sriharsha; Gounaris, Elias; Pakanati, Krishna Chaitanya

    2012-02-01

    Inflammatory bowel disease (IBD) is known for causing disturbed homeostatic balance among the intestinal immune compartment, epithelium and microbiota. Owing to the emergence of IBD as a major cause of morbidity and mortality, great efforts have been put into understanding the sequence of intestinal inflammatory events. Intestinal macrophages and dendritic cells act in a synergistic fashion with intestinal epithelial cells and microbiota to initiate the triad that governs the intestinal immune responses (whether inflammatory or regulatory). In this review, we will discuss the interplay of intestinal epithelial cells, bacteria and the innate immune component. Moreover, whether or not genetic intervention of probiotic bacteria is a valid approach for attenuating/mitigating exaggerated inflammation and IBD will also be discussed.

  9. Inflammation, immunity, and Alzheimer's disease.

    PubMed

    Town, Terrence

    2010-04-01

    Few topics in the field of Alzheimer's disease (AD) research have brought about the level of excitement and interest as the role of inflammation and immunity in the pathobiology and treatment of the disease. In this special issue of the journal, experts in the field give their views on how inflammatory processes and the immune system intersect- at both etiological and treatment levels- with disease biology. Collectively, nearly three decades of work are covered in this special issue, beginning with the first epidemiologic studies that showed an inverse risk relationship between AD and use of non-steroidal anti-inflammatory drugs, and ending with "immunotherapy" approaches and recent studies examining the roles of innate immune cells including microglia and peripheral mononuclear phagocytes in AD. Despite considerable work in this area, many important questions remain concerning the nature and timing of immune/inflammatory responses in the context of AD, and at what point and how to therapeutically intervene.

  10. Inflammation and Alzheimer’s disease

    PubMed Central

    Akiyama, Haruhiko; Barger, Steven; Barnum, Scott; Bradt, Bonnie; Bauer, Joachim; Cole, Greg M.; Cooper, Neil R.; Eikelenboom, Piet; Emmerling, Mark; Fiebich, Berndt L.; Finch, Caleb E.; Frautschy, Sally; Griffin, W.S.T.; Hampel, Harald; Hull, Michael; Landreth, Gary; Lue, Lih–Fen; Mrak, Robert; Mackenzie, Ian R.; McGeer, Patrick L.; O’Banion, M. Kerry; Pachter, Joel; Pasinetti, Guilio; Plata–Salaman, Carlos; Rogers, Joseph; Rydel, Russell; Shen, Yong; Streit, Wolfgang; Strohmeyer, Ronald; Tooyoma, Ikuo; Van Muiswinkel, Freek L.; Veerhuis, Robert; Walker, Douglas; Webster, Scott; Wegrzyniak, Beatrice; Wenk, Gary; Wyss–Coray, Tony

    2013-01-01

    Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer’s disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid β peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder. PMID:10858586

  11. [Inflammation and obesity (lipoinflammation)].

    PubMed

    Izaola, Olatz; de Luis, Daniel; Sajoux, Ignacio; Domingo, Joan Carles; Vidal, Montse

    2015-06-01

    Obesity is a chronic disease with multiple origins. It is a widespread global phenomenon carrying potentially serious complications which requires a multidisciplinary approach due to the significant clinical repercussions and elevated health costs associated with the disease. The most recent evidence indicates that it shares a common characteristic with other prevalent, difficult-to-treat pathologies: chronic, low-grade inflammation which perpetuates the disease and is associated with multiple complications. The current interest in lipoinflammation or chronic inflammation associated with obesity derives from an understanding of the alterations and remodelling that occurs in the adipose tissue, with the participation of multiple factors and elements throughout the process. Recent research highlights the importance of some of these molecules, called pro-resolving mediators, as possible therapeutic targets in the treatment of obesity. This article reviews the evidence published on the mechanisms that regulate the adipose tissue remodelling process and lipoinflammation both in obesity and in the mediators that are directly involved in the appearance and resolution of the inflammatory process.

  12. [Inflammation and obesity (lipoinflammation)].

    PubMed

    Izaola, Olatz; de Luis, Daniel; Sajoux, Ignacio; Domingo, Joan Carles; Vidal, Montse

    2015-01-01

    Obesity is a chronic disease with multiple origins. It is a widespread global phenomenon carrying potentially serious complications which requires a multidisciplinary approach due to the significant clinical repercussions and elevated health costs associated with the disease. The most recent evidence indicates that it shares a common characteristic with other prevalent, difficult-to-treat pathologies: chronic, low-grade inflammation which perpetuates the disease and is associated with multiple complications. The current interest in lipoinflammation or chronic inflammation associated with obesity derives from an understanding of the alterations and remodelling that occurs in the adipose tissue, with the participation of multiple factors and elements throughout the process. Recent research highlights the importance of some of these molecules, called pro-resolving mediators, as possible therapeutic targets in the treatment of obesity. This article reviews the evidence published on the mechanisms that regulate the adipose tissue remodelling process and lipoinflammation both in obesity and in the mediators that are directly involved in the appearance and resolution of the inflammatory process. PMID:26040339

  13. Protective role of interleukin-10 in Ozone-induced pulmonary inflammation**

    EPA Science Inventory

    Background: The mechanisms underlying ozone (03)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators. Objectives: We investigated the molecular mechanisms underlying interleuken-10...

  14. Pathogenesis of tendinopathies: inflammation or degeneration?

    PubMed Central

    Abate, Michele; Gravare-Silbernagel, Karin; Siljeholm, Carl; Di Iorio, Angelo; De Amicis, Daniele; Salini, Vincenzo; Werner, Suzanne; Paganelli, Roberto

    2009-01-01

    The intrinsic pathogenetic mechanisms of tendinopathies are largely unknown and whether inflammation or degeneration has the prominent role is still a matter of debate. Assuming that there is a continuum from physiology to pathology, overuse may be considered as the initial disease factor; in this context, microruptures of tendon fibers occur and several molecules are expressed, some of which promote the healing process, while others, including inflammatory cytokines, act as disease mediators. Neural in-growth that accompanies the neovessels explains the occurrence of pain and triggers neurogenic-mediated inflammation. It is conceivable that inflammation and degeneration are not mutually exclusive, but work together in the pathogenesis of tendinopathies. PMID:19591655

  15. Targeting inflammation in metabolic syndrome.

    PubMed

    Welty, Francine K; Alfaddagh, Abdulhamied; Elajami, Tarec K

    2016-01-01

    The metabolic syndrome (MetS) is comprised of a cluster of closely related risk factors, including visceral adiposity, insulin resistance, hypertension, high triglyceride, and low high-density lipoprotein cholesterol; all of which increase the risk for the development of type 2 diabetes and cardiovascular disease. A chronic state of inflammation appears to be a central mechanism underlying the pathophysiology of insulin resistance and MetS. In this review, we summarize recent research which has provided insight into the mechanisms by which inflammation underlies the pathophysiology of the individual components of MetS including visceral adiposity, hyperglycemia and insulin resistance, dyslipidemia, and hypertension. On the basis of these mechanisms, we summarize therapeutic modalities to target inflammation in the MetS and its individual components. Current therapeutic modalities can modulate the individual components of MetS and have a direct anti-inflammatory effect. Lifestyle modifications including exercise, weight loss, and diets high in fruits, vegetables, fiber, whole grains, and low-fat dairy and low in saturated fat and glucose are recommended as a first line therapy. The Mediterranean and dietary approaches to stop hypertension diets are especially beneficial and have been shown to prevent development of MetS. Moreover, the Mediterranean diet has been associated with reductions in total and cardiovascular mortality. Omega-3 fatty acids and peroxisome proliferator-activated receptor α agonists lower high levels of triglyceride; their role in targeting inflammation is reviewed. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone blockers comprise pharmacologic therapies for hypertension but also target other aspects of MetS including inflammation. Statin drugs target many of the underlying inflammatory pathways involved in MetS.

  16. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

  17. Medicinal plants with anti-inflammatory activities.

    PubMed

    Maione, Francesco; Russo, Rosa; Khan, Haroon; Mascolo, Nicola

    2016-06-01

    Medicinal plants have been the main remedy to treat various ailments for a long time and nowadays, many drugs have been developed from traditional medicine. This paper reviews some medicinal plants and their main constituents which possess anti-inflammatory activities useful for curing joint inflammation, inflammatory skin disorders, cardiovascular inflammation and other inflammatory diseases. Here, we provide a brief overview of quick and easy reading on the role of medicinal plants and their main constituents in these inflammatory diseases. We hope that this overview will shed some light on the function of these natural anti-inflammatory compounds and attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions. PMID:26221780

  18. Carbonaceous objects resembling nannobacteria in the Allende meteorite

    NASA Astrophysics Data System (ADS)

    Folk, Robert L.; Lynch, F. Leo

    1998-07-01

    The carbon in Allende consists of balls ranging form 30 to 150 nm in diameter.Most are spheres, but some ovoid to worm- like forms occur. Grape-like clumps and rosary-like chains are the most dramatic mimics of terrestrial bacterial colonies. We propose that the carbon balls in Allende represent roasted corpses of nanobacteria because of their resemblance to nanobacteria on earth.

  19. Familial resemblance of blood pressure and body weight.

    PubMed

    André, J L; Deschamps, J P; Gueguen, R

    1986-01-01

    Familial resemblance of blood pressure (BP) was studied in 545 families of which 370 included natural children, 24 adopted children and 151 both natural and adopted children. Mean values of four automatic BP measurements (Dinamap 845) were converted into age (adult) or height (children) and sex adjusted scores. BP was compared between parents and randomly chosen index children. A significant resemblance of BP was observed between natural children and their parents: r = 0.24 for systolic BP, r = 0.29 for diastolic BP, (n = 272 p greater than 0.05). BP of adopted children did not resemble that of their foster parents except for a significant correlation to BP of the adopting mothers (n = 46). Weight, heart rate, age and time of common life shared did not influence the results. The relative contribution of genetic and common environmental factors to BP correlation between family members could not be evaluated in this study. BP of children whose parents have high BP should be monitored regularly.

  20. Soy protein inhibits inflammation-induced VCAM-1 and inflammatory cytokine induction by inhibiting the NF-kappaB and AKT signaling pathway in apolipoprotein E-deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Inflammation is a hallmark of many diseases, such as atherosclerosis, autoimmune diseases, obesity, and cancer. Isoflavone-free soy protein diet (SPI(-)) has been shown to reduce atherosclerotic lesions in a hyperlipidemic mouse model compared to casein (CAS)-fed mice, despite unchanged ser...

  1. Inflammation: the dynamic force of health and disease.

    PubMed

    Vassileva, V; Piquette-Miller, M

    2014-10-01

    Replacing "happiness" with "inflammation" in Thomas Merton's quotation holds true for the processes that govern our immune response and health. The balance between pro- and anti-inflammatory signals regulates inflammatory responses, leading to either restoration of health or the development and progression of disease, depending on whether it creates equilibrium or dysfunction. This issue of Clinical Pharmacology & Therapeutics highlights emerging research and concepts related to inflammation and its underlying role in chronic disease and variable drug response.

  2. Chronic Inflammation in Skin Malignancies

    PubMed Central

    Tang, Lihua

    2016-01-01

    Chronic inflammation is linked to the development and progression of multiple cancers, including those of the lung, stomach, liver, colon, breast and skin. Inflammation not only drives the oncogenic transformation of epithelial cells under the stress of chronic infection and autoimmune diseases, but also promotes the growth, progression and metastatic spread of cancers. Tumor-infiltrating inflammatory cells are comprised of a diverse population of myeloid and immune cell types, including monocytes, macrophages, dendritic cells, T and B cells, and others. Different myeloid and lymphoid cells within tumor microenvironment exert diverse, often contradicting, effects during skin cancer development and progression. The nature of tumor-immune interaction determines the rate of cancer progression and the outcome of cancer treatment. Inflammatory environment within skin tumor also inhibits naturally occurring anti-tumor immunity and limits the efficacy of cancer immunotherapy. In this article we aim to give an overview on the mechanism by which inflammation interferes with the development and therapeutic intervention of cancers, especially those of the skin.

  3. Inflammation-induced thrombosis: mechanisms, disease associations and management.

    PubMed

    Aksu, Kenan; Donmez, Ayhan; Keser, Gokhan

    2012-01-01

    Although inflammation-induced thrombosis is a well-known entity, its pathogenesis remains complicated. There are complex interactions between inflammation and hemostasis, involving proinflammatory cytokines, chemokines, adhesion molecules, tissue factor expression, platelet and endothelial activation, and microparticles. Inflammation increases procoagulant factors, and also inhibits natural anticoagulant pathways and fibrinolytic activity, causing a thrombotic tendency. Besides, chronic inflammation may cause endothelial damage, resulting in the loss of physiologic anticoagulant, antiaggregant and vasodilatory properties of endothelium. However, inflammation- induced venous thrombosis may develop even in the absence of vessel wall damage. On the other hand, coagulation also augments inflammation, causing a vicious cycle. This is mainly achieved by means of thrombin-induced secretion of proinflammatory cytokines and growth factors. Platelets may also trigger inflammation by activating the dendritic cells. There are many systemic inflammatory diseases characterized by thrombotic tendency, including Behçet disease (BD), antineutrophilic cytoplasmic antibody-associated vasculitides, Takayasu arteritis, rheumatoid arthritis, systemic lupus erythematosus, antiphosholipid syndrome, familial Mediterranean fever, thromboangiitis obliterans (TAO) and inflammatory bowel diseases. Inflammation-induced thrombosis may respond to immunosuppressive (IS) treatment, as in the case of BD. However effectiveness of this treatment can not be generalized to all other inflammatory diseases. For instance, IS agents do not have any beneficial role in the management of TAO. Heparin, antiplatelet agents such as aspirin and clopidogrel, colchicine and statins also have some antiinflammatory activity. However, decreased responsiveness to aspirin and clopidogrel treatments may be observed in inflammatory diseases, due to antiplatelet resistance caused by systemic inflammation. In the present

  4. Does Inflammation Mediate the Association Between Obesity and Insulin Resistance?

    PubMed

    Adabimohazab, Razieh; Garfinkel, Amanda; Milam, Emily C; Frosch, Olivia; Mangone, Alexander; Convit, Antonio

    2016-06-01

    In adult obesity, low-grade systemic inflammation is considered an important step in the pathogenesis of insulin resistance (IR). The association between obesity and inflammation is less well established in adolescents. Here, we ascertain the importance of inflammation in IR among obese adolescents by utilizing either random forest (RF) classification or mediation analysis approaches. The inflammation balance score, composed of eight pro- and anti-inflammatory makers, as well as most of the individual inflammatory markers differed significantly between lean and overweight/obese. In contrast, adiponectin was the only individual marker selected as a predictor of IR by RF, and the balance score only revealed a medium-to-low importance score. Neither adiponectin nor the inflammation balance score was found to mediate the relationship between obesity and IR. These findings do not support the premise that low-grade systemic inflammation is a key for the expression of IR in the human. Prospective longitudinal studies should confirm these findings.

  5. Reactive Oxygen Species in Inflammation and Tissue Injury

    PubMed Central

    Mittal, Manish; Siddiqui, Mohammad Rizwan; Tran, Khiem; Reddy, Sekhar P.

    2014-01-01

    Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury. Antioxid. Redox Signal. 20, 1126–1167. PMID:23991888

  6. Atherosclerosis is an inflammatory disorder after all.

    PubMed

    Meng, Charles Q

    2006-01-01

    Inflammation has been increasingly recognized as an important player in the pathophysiology of numerous human disorders. Accumulating evidence has led to the conclusion that atherosclerosis is an inflammatory disease, although it was believed to be a disorder of high cholesterol levels in the bloodstream for over a century. Cholesterol does contribute to the pathogenesis of atherosclerosis, but through inflammatory mechanisms. Statins lower cholesterol levels and hence reduce inflammation in the vasculature and prevent heart disease. Statins may also exert anti-inflammatory effects through mechanisms independent of cholesterol lowering. Adhesion molecules, cytokines, oxidative stress, etc. appear to contribute to the inflammatory state of atherosclerosis and therapeutic approaches directed toward these markers or targets have the potential to be effective in reducing inflammation and treating atherosclerosis. PMID:16454761

  7. Inflammation in atherosclerosis: new opportunities for drug discovery.

    PubMed

    Meng, Charles Q

    2005-01-01

    Many lines of evidence indicate that inflammation is the ultimate cause of atherosclerosis; high cholesterol levels cause atherosclerosis through mechanism of inflammation. Drugs designed to address inflammatory aspects of atherosclerosis will likely be more effective than current therapies in treating and preventing coronary artery disease. PMID:15638790

  8. Inflammation and oxidative stress in vertebrate host-parasite systems.

    PubMed

    Sorci, Gabriele; Faivre, Bruno

    2009-01-12

    Innate, inflammation-based immunity is the first line of vertebrate defence against micro-organisms. Inflammation relies on a number of cellular and molecular effectors that can strike invading pathogens very shortly after the encounter between inflammatory cells and the intruder, but in a non-specific way. Owing to this non-specific response, inflammation can generate substantial costs for the host if the inflammatory response, and the associated oxygen-based damage, get out of control. This imposes strong selection pressure that acts to optimize two key features of the inflammatory response: the timing of activation and resolution (the process of downregulation of the response). In this paper, we review the benefits and costs of inflammation-driven immunity. Our aim is to emphasize the importance of resolution of inflammation as a way of maintaining homeostasis against oxidative stress and to prevent the 'horror autotoxicus' of chronic inflammation. Nevertheless, host immune regulation also opens the way to pathogens to subvert host defences. Therefore, quantifying inflammatory costs requires assessing (i) short-term negative effects, (ii) delayed inflammation-driven diseases, and (iii) parasitic strategies to subvert inflammation. PMID:18930878

  9. Inflammation-inducing Factors of Mycoplasma pneumoniae

    PubMed Central

    Shimizu, Takashi

    2016-01-01

    Mycoplasma pneumoniae, which causes mycoplasmal pneumonia in human, mainly causes pneumonia in children, although it occasionally causes disease in infants and geriatrics. Some pathogenic factors produced by M. pneumoniae, such as hydrogen peroxide and Community-Acquired Respiratory Distress Syndrome (CARDS) toxin have been well studied. However, these factors alone cannot explain this predilection. The low incidence rate of mycoplasmal pneumonia in infants and geriatrics implies that the strong inflammatory responses induced by M. pneumoniae coordinate with the pathogenic factors to induce pneumonia. However, M. pneumoniae lacks a cell wall and does not possess an inflammation-inducing endotoxin, such as lipopolysaccharide (LPS). In M. pneumoniae, lipoproteins were identified as an inflammation-inducing factor. Lipoproteins induce inflammatory responses through Toll-like receptors (TLR) 2. Because Mycoplasma species lack a cell wall and lipoproteins anchored in the membrane are exposed, lipoproteins and TLR2 have been thought to be important for the pathogenesis of M. pneumoniae. However, recent reports suggest that M. pneumoniae also induces inflammatory responses also in a TLR2-independent manner. TLR4 and autophagy are involved in this TLR2-independent inflammation. In addition, the CARDS toxin or M. pneumoniae cytadherence induces inflammatory responses through an intracellular receptor protein complex called the inflammasome. In this review, the inflammation-inducing factors of M. pneumoniae are summarized. PMID:27065977

  10. Neurobiology of Inflammation-Associated Anorexia

    PubMed Central

    Gautron, Laurent; Layé, Sophie

    2009-01-01

    Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients. PMID:20582290

  11. Effects of hemodiafiltration on uremic inflammation.

    PubMed

    Leurs, Paul; Lindholm, Bengt; Stenvinkel, Peter

    2013-01-01

    Chronic inflammation is highly prevalent among end-stage renal disease patients and is linked to, and thought to contribute to, the high morbidity and mortality in this patient population. Hemodiafiltration (HDF) may potentially reduce inflammatory stimuli induced by the bioincompatibility of conventional hemodialysis (HD) systems. In addition, HDF may more efficiently remove inflammatory mediators. This brief review shows that the circulating levels of various markers of systemic inflammation in general are somewhat reduced in patients treated by HDF as compared to HD. On the other hand, according to the current literature, this favorable small impact on inflammation biomarkers does not seem to translate into better clinical outcomes. It is possible that this is due to inadequate design, inadequate number of investigated patients and too short duration of previous studies. The results of larger, better-designed ongoing prospective studies may hopefully clarify this.

  12. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma

    PubMed Central

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh

    2016-01-01

    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene. PMID:27625493

  13. Carisoprodol withdrawal syndrome resembling neuroleptic malignant syndrome: Diagnostic dilemma.

    PubMed

    Paul, Gunchan; Parshotam, Gautam L; Garg, Rajneesh

    2016-01-01

    Soma (Carisoprodol) is N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; a commonly prescribed, centrally acting skeletal muscle relaxant. Neuroleptic malignant syndrome (NMS) is a potentially life-threatening adverse effect of antipsychotic agents. Although diagnostic criteria for NMS have been established, it should be recognized that atypical presentations occur and more flexible diagnostic criteria than currently mandated, may be warranted. We wish to report a postoperative case of bilateral knee replacement who presented with carisoprodol (Soma) withdrawal resembling NMS that was a diagnostic dilemma. Subsequently, it was successfully treated with oral baclofen in absence of sodium dantrolene. PMID:27625493

  14. Molecular cues guiding inflammatory responses.

    PubMed

    Barreiro, Olga; Martín, Pilar; González-Amaro, Roberto; Sánchez-Madrid, Francisco

    2010-05-01

    Alarm signals generated at inflammatory foci reach the vascular lumen to attract immune cells towards the affected tissue. Different leucocyte subsets decipher and integrate these complex signals in order to make adequate decisions for their migration towards the inflamed tissue. Soluble cues (cytokines and chemokines) and membrane receptors in both endothelium and leucocytes orchestrate the coordinated recruitment of specific inflammatory cell subsets. All these molecules are spatio-temporally organized in specialized structures at the luminal side of endothelium and the leucocyte membrane or are generated as chemical gradients in the damaged tissue. Thus, the repertoire of chemokines and their receptors as well as adhesion molecules expressed by each leucocyte subset determine their recruitment for participation in specific inflammatory pathologies. Whenever inflammatory signals are altered or misprocessed, inflammation can become chronic, causing extensive tissue damage. To combat chronic inflammation and autoimmune diseases, novel therapeutic strategies attempt to silence the predominant signals in each inflammatory scenario. In this review, we provide a general overview of all these aspects related to the molecular regulation of leucocyte guidance in inflammatory responses.

  15. Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model.

    PubMed

    Gröger, Marko; Rennert, Knut; Giszas, Benjamin; Weiß, Elisabeth; Dinger, Julia; Funke, Harald; Kiehntopf, Michael; Peters, Frank T; Lupp, Amelie; Bauer, Michael; Claus, Ralf A; Huber, Otmar; Mosig, Alexander S

    2016-02-23

    Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes.

  16. Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model

    PubMed Central

    Gröger, Marko; Rennert, Knut; Giszas, Benjamin; Weiß, Elisabeth; Dinger, Julia; Funke, Harald; Kiehntopf, Michael; Peters, Frank T.; Lupp, Amelie; Bauer, Michael; Claus, Ralf A.; Huber, Otmar; Mosig, Alexander S.

    2016-01-01

    Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes. PMID:26902749

  17. Silibinin attenuates allergic airway inflammation in mice

    SciTech Connect

    Choi, Yun Ho; Jin, Guang Yu; Guo, Hui Shu; Piao, Hong Mei; Li, Liang chang; Li, Guang Zhao; Lin, Zhen Hua; Yan, Guang Hai

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Silibinin diminishes ovalbumin-induced inflammatory reactions in the mouse lung. Black-Right-Pointing-Pointer Silibinin reduces the levels of various cytokines into the lung of allergic mice. Black-Right-Pointing-Pointer Silibinin prevents the development of airway hyperresponsiveness in allergic mice. Black-Right-Pointing-Pointer Silibinin suppresses NF-{kappa}B transcriptional activity. -- Abstract: Allergic asthma is a chronic inflammatory disease regulated by coordination of T-helper2 (Th2) type cytokines and inflammatory signal molecules. Silibinin is one of the main flavonoids produced by milk thistle, which is reported to inhibit the inflammatory response by suppressing the nuclear factor-kappa B (NF-{kappa}B) pathway. Because NF-{kappa}B activation plays a pivotal role in the pathogenesis of allergic inflammation, we have investigated the effect of silibinin on a mouse ovalbumin (OVA)-induced asthma model. Airway hyperresponsiveness, cytokines levels, and eosinophilic infiltration were analyzed in bronchoalveolar lavage fluid and lung tissue. Pretreatment of silibinin significantly inhibited airway inflammatory cell recruitment and peribronchiolar inflammation and reduced the production of various cytokines in bronchoalveolar fluid. In addition, silibinin prevented the development of airway hyperresponsiveness and attenuated the OVA challenge-induced NF-{kappa}B activation. These findings indicate that silibinin protects against OVA-induced airway inflammation, at least in part via downregulation of NF-{kappa}B activity. Our data support the utility of silibinin as a potential medicine for the treatment of asthma.

  18. Gaseous mediators in resolution of inflammation.

    PubMed

    Wallace, John L; Ianaro, Angela; Flannigan, Kyle L; Cirino, Giuseppe

    2015-05-01

    There are numerous gaseous substances that can act as signaling molecules, but the best characterized of these are nitric oxide, hydrogen sulfide and carbon monoxide. Each has been shown to play important roles in many physiological and pathophysiological processes. This article is focused on the effects of these gasotransmitters in the context of inflammation. There is considerable overlap in the actions of nitric oxide, hydrogen sulfide and carbon monoxide with respect to inflammation, and these mediators appear to act primarily as anti-inflammatory substances, promoting resolution of inflammatory processes. They also have protective and pro-healing effects in some tissues, such as the gastrointestinal tract and lung. Over the past two decades, significant progress has been made in the development of novel anti-inflammatory and cytoprotective drugs that release of one or more of these gaseous mediators.

  19. The role of cytokines in pulp inflammation.

    PubMed

    Kokkas, A; Goulas, A; Stavrianos, C; Anogianakis, G

    2011-01-01

    Pulpitis is a typical inflammatory disease of dental pulp, characterized by the local accumulation of inflammatory mediators, including cytokines and chemokines. In addition to serving as intercellular messengers mediating the inflammatory response, cytokines and chemokines induce the expression and stimulate the activity of molecular and cellular agents which participate actively in destructive and reparative processes in the pulp. It is the balance between these processes which eventually determines the extent of pulp inflammation and the viability of the affected tooth. Over the last decade, a number of studies have attempted to correlate cytokine gene expression in the pulp with various stages of inflammation, with possible diagnostic applications in mind. A small survey of relevant information is presented in this paper.

  20. Infections, inflammation and epilepsy.

    PubMed

    Vezzani, Annamaria; Fujinami, Robert S; White, H Steve; Preux, Pierre-Marie; Blümcke, Ingmar; Sander, Josemir W; Löscher, Wolfgang

    2016-02-01

    Epilepsy is the tendency to have unprovoked epileptic seizures. Anything causing structural or functional derangement of brain physiology may lead to seizures, and different conditions may express themselves solely by recurrent seizures and thus be labelled "epilepsy." Worldwide, epilepsy is the most common serious neurological condition. The range of risk factors for the development of epilepsy varies with age and geographic location. Congenital, developmental and genetic conditions are mostly associated with the development of epilepsy in childhood, adolescence and early adulthood. Head trauma, infections of the central nervous system (CNS) and tumours may occur at any age and may lead to the development of epilepsy. Infections of the CNS are a major risk factor for epilepsy. The reported risk of unprovoked seizures in population-based cohorts of survivors of CNS infections from developed countries is between 6.8 and 8.3 %, and is much higher in resource-poor countries. In this review, the various viral, bacterial, fungal and parasitic infectious diseases of the CNS which result in seizures and epilepsy are discussed. The pathogenesis of epilepsy due to brain infections, as well as the role of experimental models to study mechanisms of epileptogenesis induced by infectious agents, is reviewed. The sterile (non-infectious) inflammatory response that occurs following brain insults is also discussed, as well as its overlap with inflammation due to infections, and the potential role in epileptogenesis. Furthermore, autoimmune encephalitis as a cause of seizures is reviewed. Potential strategies to prevent epilepsy resulting from brain infections and non-infectious inflammation are also considered.

  1. Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis.

    PubMed

    Kuwabara, Yoshimitsu; Sato, Atsuki; Abe, Hiroko; Abe, Sumino; Kawai, Naoki; Takeshita, Toshiyuki

    2011-01-01

    A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis.

  2. [Osteoid osteoma of the wrist joint resembling tenosynovitis].

    PubMed

    Volpin, Gershon; Shtarker, Haim; Oliver, Simon; Katznelson, Alexander; Stahl, Shalom

    2006-12-01

    Osteoid osteoma of bones of the wrist joint is a relatively rare lesion. This article presents a series of three patients, one with osteoid osteoma of the styloid process of the radius and two with osteoid osteoma of the capitate bone. All of them had clinical symptoms resembling those of stenosing tenosynovitis of the wrist joint. X-rays, tomography and bone scan revealed the characteristic findings of osteoid osteoma. Histological examination confirmed the diagnosis. Treatment consisted of "en bloc" excision of these tumors. Following surgery patients were asymptomatic and had normal mobility of the affected wrist. In the first patient this has been maintained for the succeeding 27 years. It is suggested that in any case of persistent unexplained pain of the wrist or clinical symptoms resembling those of tenosynovitis, osteoid osteoma of the styloid process of the radius or of the carpal bones should also be included in the differential diagnosis. The recommended treatment of osteoid osteoma is "en bloc" excision of this tumour in the affected bone, resulting in complete relief of pain and absence of functional disturbances. PMID:17220026

  3. Ritodrine-induced pustular eruptions distinctly resembling impetigo herpetiformis.

    PubMed

    Kuwabara, Yoshimitsu; Sato, Atsuki; Abe, Hiroko; Abe, Sumino; Kawai, Naoki; Takeshita, Toshiyuki

    2011-01-01

    A 27-year-old nulligravida woman without a history of dermatosis was hospitalized for threatened preterm labor at 29 weeks' gestation; therefore, continuous infusion of ritodrine hydrochloride was started. At 31 weeks' gestation, erythematous plaques appeared and spread over the body surface; therefore, a topical steroid preparation was applied. At 32 weeks' gestation, the eruptions developed into irregular annular areas of erythema with multiple pustules accompanied by severe itching, and oral prednisolone treatment was started. Bacterial cultures of the pustules were negative, and a crural cutaneous biopsy revealed Kogoj's spongiform pustules. Based on the clinicopathological findings, the most likely diagnosis was impetigo herpetiformis, which causes cutaneous symptoms closely resembling pustular psoriasis in pregnant females without a history of psoriasis. To rule out ritodrine-induced pustular eruptions, the ritodrine infusion was stopped and treatment with an MgSO(4) preparation was started at 33 weeks' 3 days' gestation; however, the uterine contractions could not be suppressed. Because of the patient's highly edematous, severely painful feet, a cesarean section was performed the same day. Within several days of delivery, the eruptions began to resolve, and no recurrence was observed after treatment with oral prednisolone was stopped 31 days after delivery. On the basis of a positive patch test for ritodrine, we diagnosed pustular drug eruptions caused by ritodrine hydrochloride. Although ritodrine-induced pathognomonic cutaneous eruptions are rare, we would like to emphasize that ritodrine can cause drug-induced pustular eruptions distinctly resembling life-threatening impetigo herpetiformis. PMID:22041881

  4. Chemokines in cancer related inflammation

    SciTech Connect

    Allavena, Paola; Germano, Giovanni; Marchesi, Federica; Mantovani, Alberto

    2011-03-10

    Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.

  5. Selenium and inflammatory bowel disease.

    PubMed

    Kudva, Avinash K; Shay, Ashley E; Prabhu, K Sandeep

    2015-07-15

    Dietary intake of the micronutrient selenium is essential for normal immune functions. Selenium is cotranslationally incorporated as the 21st amino acid, selenocysteine, into selenoproteins that function to modulate pathways involved in inflammation. Epidemiological studies have suggested an inverse association between selenium levels and inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis that can potentially progress to colon cancer. However, the underlying mechanisms are not well understood. Here we summarize the current literature on the pathophysiology of IBD, which is multifactorial in origin with unknown etiology. We have focused on a few selenoproteins that mediate gastrointestinal inflammation and activate the host immune response, wherein macrophages play a pivotal role. Changes in cellular oxidative state coupled with altered expression of selenoproteins in macrophages drive the switch from a proinflammatory phenotype to an anti-inflammatory phenotype to efficiently resolve inflammation in the gut and restore epithelial barrier integrity. Such a phenotypic plasticity is accompanied by changes in cytokines, chemokines, and bioactive metabolites, including eicosanoids that not only mitigate inflammation but also partake in restoring gut homeostasis through diverse pathways involving differential regulation of transcription factors such as nuclear factor-κB and peroxisome proliferator-activated receptor-γ. The role of the intestinal microbiome in modulating inflammation and aiding in selenium-dependent resolution of gut injury is highlighted to provide novel insights into the beneficial effects of selenium in IBD.

  6. Preclinical Assessment of Inflammatory Pain.

    PubMed

    Muley, Milind M; Krustev, Eugene; McDougall, Jason J

    2016-02-01

    While acute inflammation is a natural physiological response to tissue injury or infection, chronic inflammation is maladaptive and engenders a considerable amount of adverse pain. The chemical mediators responsible for tissue inflammation act on nociceptive nerve endings to lower neuronal excitation threshold and sensitize afferent firing rate leading to the development of allodynia and hyperalgesia, respectively. Animal models have aided in our understanding of the pathophysiological mechanisms responsible for the generation of chronic inflammatory pain and allowed us to identify and validate numerous analgesic drug candidates. Here we review some of the commonly used models of skin, joint, and gut inflammatory pain along with their relative benefits and limitations. In addition, we describe and discuss several behavioral and electrophysiological approaches used to assess the inflammatory pain in these preclinical models. Despite significant advances having been made in this area, a gap still exists between fundamental research and the implementation of these findings into a clinical setting. As such we need to characterize inherent pathophysiological pathways and develop new endpoints in these animal models to improve their predictive value of human inflammatory diseases in order to design safer and more effective analgesics.

  7. YKL-40/CHI3L1 drives inflammation on the road of tumor progression.

    PubMed

    Libreros, Stephania; Iragavarapu-Charyulu, Vijaya

    2015-12-01

    Inflammation plays a vital role at different stages of tumor progression. The development of tumors is affected by inflammatory mediators produced by the tumor and the host. YKL-40/chitinase-3-like-1 protein is often up-regulated in inflammation-associated diseases. With the use of chronic inflammatory disease systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing the inflammatory response and its implications in tumorigenesis. We also discuss how pre-existing inflammation enhances tumor growth and metastasis. In this mini-review, we highlight the effect of YKL-40/chitinase-3-like-1 protein-associated inflammation in promoting tumor progression. PMID:26310833

  8. Blood coagulation and fibrinolysis in aortic valve stenosis: links with inflammation and calcification.

    PubMed

    Natorska, J; Undas, A

    2015-08-01

    Aortic valve stenosis (AS) increasingly afflicts our aging population. However, the pathobiology of the disease is still poorly understood and there is no effective pharmacotherapy for treating those at risk for clinical progression. The progression of AS involves complex inflammatory and fibroproliferative processes that resemble to some extent atherosclerosis. Accumulating evidence indicates that several coagulation proteins and its inhibitors, including tissue factor, tissue factor pathway inhibitor, prothrombin, factor XIII, von Willebrand factor, display increased expression within aortic stenotic valves, predominantly on macrophages and myofibroblasts around calcified areas. Systemic impaired fibrinolysis, along with increased plasma and valvular expression of plasminogen activator inhibitor-1, has also been observed in patients with AS in association with the severity of the disease. There is an extensive cross-talk between inflammation and coagulation in stenotic valve tissue which contributes to the calcification and mineralisation of the aortic valve leaflets. This review summarises the available data on blood coagulation and fibrinolysis in AS with the emphasis on their interactions with inflammation and calcification.

  9. Chronic inflammation and pancreatic cancer.

    PubMed

    McKay, Colin J; Glen, Paul; McMillan, Donald C

    2008-01-01

    There is a proven association between carcinoma of the pancreas and both the sporadic and hereditary forms of chronic pancreatitis. In chronic pancreatitis the standardised incidence ratio for development of pancreatic cancer is 14-18 and is further increased by cigarette smoking. Underlying mechanisms are unclear but current theories point to the progressive accumulation of genetic mutations as a consequence of repeated DNA damage and cell regeneration in an environment favouring proliferation and neovascularisation. In patients who develop pancreatic cancer, there is interest in the role of the inflammatory response in the development of cancer cachexia and in determining prognosis. Furthermore, markers of a systemic inflammatory response have prognostic significance in both advanced, inoperable pancreatic cancer and in patients undergoing resection. Further understanding of the details of the relationship between inflammation, carcinogenesis and cancer prognosis may lead to new therapeutic possibilities as part of multi-modality management of this difficult disease.

  10. Coagulation and inflammation. Molecular insights and diagnostic implications.

    PubMed

    Lipinski, S; Bremer, L; Lammers, T; Thieme, F; Schreiber, S; Rosenstiel, P

    2011-05-01

    Overwhelming evidence has linked inflammatory disorders to a hypercoagulable state. In fact, thromboembolic complications are among the leading causes of disability and death in many acute and chronic inflammatory diseases. Despite this clinical knowledge, coagulation and immunity were long regarded as separate entities. Recent studies have unveiled molecular underpinnings of the intimate interconnection between both systems. The studies have clearly shown that distinct pro-inflammatory stimuli also activate the clotting cascade and that coagulation in turn modulates inflammatory signaling pathways. In this review, we use evidence from sepsis and inflammatory bowel diseases as a paradigm for acute and chronic inflammatory states in general and rise hypotheses how a systematic molecular understanding of the "inflammation-coagulation" crosstalk may result in novel diagnostic and therapeutic strategies that target the inflammation-induced hypercoagulable state. PMID:21152678

  11. Vitamin D in inflammatory diseases

    PubMed Central

    Wöbke, Thea K.; Sorg, Bernd L.; Steinhilber, Dieter

    2014-01-01

    Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq. PMID:25071589

  12. Role of inflammation in cardiopulmonary health effects of PM

    SciTech Connect

    Donaldson, Ken . E-mail: ken.donaldson@ed.ac.uk; Mills, Nicholas; MacNee, William; Robinson, Simon; Newby, David

    2005-09-01

    The relationship between increased exposure to PM and adverse cardiovascular effects is well documented in epidemiological studies. Inflammation in the lungs, caused by deposited particles, can be seen as a key process that could mediate adverse effects on the cardiovascular system. There are at least three potential pathways that could lead from pulmonary inflammation to adverse cardiovascular effects. Firstly, inflammation in the lung could lead to systemic inflammation, which is well known to be linked to sudden death from cardiovascular causes. Systemic inflammation can lead to destabilization by activation of inflammatory processes in atheromatous plaques. Secondly, inflammation can cause an imbalance in coagulation factors that favor propagation of thrombi if thrombosis is initiated. Thirdly, inflammation could affect the autonomic nervous system activity in ways that could lead to alterations in the control of heart rhythm which could culminate in fatal dysrhythmia.

  13. The evolution of inflammatory mediators

    PubMed Central

    Rowley, Andrew F.

    1996-01-01

    Invertebrates do not display the level of sophistication in immune reactivity characteristic of mammals and other ‘higher’ vertebrates. Their great number and diversity of forms, however, reflect their evolutionary success and hence they must have effective mechanisms of defence to deal with parasites and pathogens and altered self tissues. Inflammation appears to be an important first line defence in all invertebrates and vertebrates. This brief review deals with the inflammatory responses of invertebrates and fish concentrating on the cell types involved and the mediators of inflammation, in particular, eicosanoids, cytokines and adhesion molecules. PMID:18475690

  14. Dietary supplementation of omega-3 fatty acid-containing fish oil suppresses F2-isoprostanes but enhances inflammatory cytokine response in a mouse model of ovalbumin-induced allergic lung inflammation.

    PubMed

    Yin, Huiyong; Liu, Wei; Goleniewska, Kasia; Porter, Ned A; Morrow, Jason D; Peebles, R Stokes

    2009-09-01

    Epidemiological and clinical evidence has suggested that increased dietary intake of fish oil containing omega-3 fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be associated with a reduced risk of asthma. However, interventional studies on these effects have been equivocal and controversial. Free radical oxidation products of lipids and cyclooxygenases-derived prostaglandins are believed to play an important role in asthma, and fish oil supplementation may modulate the levels of these critical lipid mediators. We employed a murine model of allergic inflammation produced by sensitization to ovalbumin (OVA) to study the effects of fish oil supplementation on airway inflammation. Our studies demonstrated that omega-3 fatty acids were dose dependently incorporated into mouse lung tissue after dietary supplementation. We examined the oxidative stress status by measuring the levels of isoprostanes (IsoPs), the gold standard for oxidative stress in vivo. OVA challenge caused significant increase of F(2)-IsoPs in mouse lung, suggesting an elevated level of oxidative stress. Compared to the control group, fish oil supplementation led to a significant reduction of F(2)-IsoP (from arachidonic acid) with a concomitant increase of F(3)-IsoPs (from EPA) and F(4)-IsoPs (from DHA). Surprisingly, however, fish oil supplementation enhanced production of proinflammatory cytokine IL-5 and IL-13. Furthermore, fish oil supplementation suppressed the production of pulmonary protective PGE(2) in the bronchoalveolar lavage (BAL) while the level of urinary metabolites of the PGE(2) was increased. Our data suggest that augmented lung inflammation after fish oil supplementation may be due to the reduction of PGE(2) production in the lung and these dichotomous results bring into question the role of fish oil supplementation in the treatment of asthma.

  15. Role of Antioxidants and Natural Products in Inflammation

    PubMed Central

    Fard, Masoumeh Tangestani; Tan, Woan Sean; Gothai, Sivapragasam; Kumar, S. Suresh

    2016-01-01

    Inflammation is a comprehensive array of physiological response to a foreign organism, including human pathogens, dust particles, and viruses. Inflammations are mainly divided into acute and chronic inflammation depending on various inflammatory processes and cellular mechanisms. Recent investigations have clarified that inflammation is a major factor for the progression of various chronic diseases/disorders, including diabetes, cancer, cardiovascular diseases, eye disorders, arthritis, obesity, autoimmune diseases, and inflammatory bowel disease. Free radical productions from different biological and environmental sources are due to an imbalance of natural antioxidants which further leads to various inflammatory associated diseases. In this review article, we have outlined the inflammatory process and its cellular mechanisms involved in the progression of various chronic modern human diseases. In addition, we have discussed the role of free radicals-induced tissue damage, antioxidant defence, and molecular mechanisms in chronic inflammatory diseases/disorders. The systematic knowledge regarding the role of inflammation and its associated adverse effects can provide a clear understanding in the development of innovative therapeutic targets from natural sources that are intended for suppression of various chronic inflammations associated diseases. PMID:27803762

  16. Uterine tumors resembling ovarian sex cord tumors: an update.

    PubMed

    Czernobilsky, Bernard

    2008-04-01

    Tumors of the uterus resembling ovarian sex cord tumors were reported by Clement and Scully in 1976 and were divided in 2 groups: group 1, endometrial stromal tumors, and group 2, mural uterine tumors-both with elements resembling ovarian sex cord tumors. In the former, the sex cord component constitutes a minor portion of an endometrial stromal neoplasm, whereas in the latter, it is the predominant or exclusive component of a uterine wall lesion composed of a variety of mesenchymal elements. An origin from endometrial stromal cells, adenomyosis, stromal myosis, endometriosis, or multipotential cells within the myometrium was postulated in both groups of tumors. In group 1 tumors, the prognosis depends on the type, grade, and stage of the underlying stromal neoplasm. Group 2 tumors seemed to be benign, although because of the occasional recurrence of these tumors, they should be considered of low-grade malignant potential. In recent years, the histological features in group 2 were found to be much more varied than those in group 1 and consisted among others of retiform areas, glomeruloid structures, and Leydig-like cells. In group 1 tumors, the sex cord elements remained limited to cords, trabeculae, nests, and tubules. Eventually, the abbreviation ESTSCLE, or endometrial stromal tumors with sex cord-like elements, was given to group 1 tumors, whereas UTROSCT, or uterine tumor resembling ovarian sex cord tumor, was used for group 2 tumors. The most significant information in recently conducted studies concerns the immunophenotype of these lesions especially of UTROSCT. Out of the plethora of the immunohistochemical stains, a panel of 4 including calretinin, inhibin, CD99, and Melan A has emerged which seemed to be the most characteristic sex cord markers. Positivity for calretinin and at least for 1 of the other above-mentioned markers may thus confirm the diagnosis of UTROSCT. Endometrial stromal tumors with sex cord-like elements, on the other hand, usually

  17. Inflammatory mediators in acute pancreatitis.

    PubMed

    Bhatia, M; Brady, M; Shokuhi, S; Christmas, S; Neoptolemos, J P; Slavin, J

    2000-02-01

    Inflammatory mediators play a key role in acute pancreatitis and the resultant multiple organ dysfunction syndrome, which is the primary cause of death in this condition. Recent studies have confirmed the critical role played by inflammatory mediators such as TNF-alpha, IL-1beta, IL-6, IL-8, PAF, IL-10, C5a, ICAM-1, and substance P. The systemic effects of acute pancreatitis have many similarities to those of other conditions such as septicaemia, severe burns, and trauma. The delay between the onset of inflammation in the pancreas and the development of the systemic response makes acute pancreatitis an ideal experimental and clinical model with which to study the role of inflammatory mediators and to test novel therapies. Elucidation of the key mediators involved in the pathogenesis of acute pancreatitis will facilitate the development of clinically effective anti-inflammatory therapy.

  18. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?

    PubMed Central

    Hussain, Tarique; Yin, Yulong; Blachier, Francois; Tossou, Myrlene C. B.; Rahu, Najma

    2016-01-01

    Oxidative stress is viewed as an imbalance between the production of reactive oxygen species (ROS) and their elimination by protective mechanisms, which can lead to chronic inflammation. Oxidative stress can activate a variety of transcription factors, which lead to the differential expression of some genes involved in inflammatory pathways. The inflammation triggered by oxidative stress is the cause of many chronic diseases. Polyphenols have been proposed to be useful as adjuvant therapy for their potential anti-inflammatory effect, associated with antioxidant activity, and inhibition of enzymes involved in the production of eicosanoids. This review aims at exploring the properties of polyphenols in anti-inflammation and oxidation and the mechanisms of polyphenols inhibiting molecular signaling pathways which are activated by oxidative stress, as well as the possible roles of polyphenols in inflammation-mediated chronic disorders. Such data can be helpful for the development of future antioxidant therapeutics and new anti-inflammatory drugs. PMID:27738491

  19. Diabetes tolerogenic vaccines targeting antigen-specific inflammation.

    PubMed

    Geng, Shuang; Zhang, Huiyuan; Zhou, Xian; He, Yue; Zhang, Xiaoqian; Xie, Xiaoping; Li, Chaofan; He, Zhonghuai; Yu, Qingling; Zhong, Yiwei; Lowrie, Douglas B; Zheng, Guoxing; Wang, Bin

    2015-01-01

    Tolerance controls the magnitude of inflammation, and balance between beneficial and harmful effects of inflammation is crucial for organ function and survival. Inadequate tolerance leads to various inflammatory diseases. Antigen specific tolerance is ideal for inflammation control as alternative anti-inflammatory interventions are non-specific and consequently increase the risk of infection and tumorigenesis. With inherent antigen specificity, tolerogenic vaccines are potentially ideal for control of inflammation. Although the concept of tolerogenic vaccines is still in its infancy, tolerogenic mucosal vaccines and specific immuno-therapies have long been proven effective in pioneering examples. Now a body of evidence supporting the concept of tolerogenic vaccines has also accumulated. Here we comment on recent successes of the tolerogenic vaccine concept, present new evidence with a type 1 diabetes vaccine as an example and draw conclusions on the advantages and potential for inflammatory disease control at the bedside.

  20. Mouse models of intestinal inflammation and cancer.

    PubMed

    Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H

    2016-09-01

    Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With

  1. Inflammation in pulmonary arterial hypertension.

    PubMed

    Price, Laura C; Wort, S John; Perros, Frédéric; Dorfmüller, Peter; Huertas, Alice; Montani, David; Cohen-Kaminsky, Sylvia; Humbert, Marc

    2012-01-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling of the precapillary pulmonary arteries, with excessive proliferation of vascular cells. Although the exact pathophysiology remains unknown, there is increasing evidence to suggest an important role for inflammation. Firstly, pathologic specimens from patients with PAH reveal an accumulation of perivascular inflammatory cells, including macrophages, dendritic cells, T and B lymphocytes, and mast cells. Secondly, circulating levels of certain cytokines and chemokines are elevated, and these may correlate with a worse clinical outcome. Thirdly, certain inflammatory conditions such as connective tissue diseases are associated with an increased incidence of PAH. Finally, treatment of the underlying inflammatory condition may alleviate the associated PAH. Underlying pathologic mechanisms are likely to be "multihit" and complex. For instance, the inflammatory response may be regulated by bone morphogenetic protein receptor type 2 (BMPR II) status, and, in turn, BMPR II expression can be altered by certain cytokines. Although antiinflammatory therapies have been effective in certain connective-tissue-disease-associated PAH, this approach is untested in idiopathic PAH (iPAH). The potential benefit of antiinflammatory therapies in iPAH is of importance and requires further study. PMID:22215829

  2. Inflammation in Alzheimer's disease: relevance to pathogenesis and therapy

    PubMed Central

    2010-01-01

    Evidence for the involvement of inflammatory processes in the pathogenesis of Alzheimer's disease (AD) has been documented for a long time. However, the inflammation hypothesis in relation to AD pathology has emerged relatively recently. Even in this hypothesis, the inflammatory reaction is still considered to be a downstream effect of the accumulated proteins (amyloid beta (Aβ) and tau). This review aims to highlight the importance of the immune processes involved in AD pathogenesis based on the outcomes of the two major inflammation-relevant treatment strategies against AD developed and tested to date in animal studies and human clinical trials - the use of anti-inflammatory drugs and immunisation against Aβ. PMID:20122289

  3. Anti-Inflammatory Iridoids of Botanical Origin

    PubMed Central

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer’s disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective anti-inflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  4. T-cell immunosenescence and inflammatory response in atomic bomb survivors.

    PubMed

    Kusunoki, Yoichiro; Yamaoka, Mika; Kubo, Yoshiko; Hayashi, Tomonori; Kasagi, Fumiyoshi; Douple, Evan B; Nakachi, Kei

    2010-12-01

    In this paper we summarize the long-term effects of A-bomb radiation on the T-cell system and discuss the possible involvement of attenuated T-cell immunity in the disease development observed in A-bomb survivors. Our previous observations on such effects include impaired mitogen-dependent proliferation and IL-2 production, decreases in naive T-cell populations, and increased proportions of anergic and functionally weak memory CD4 T-cell subsets. In addition, we recently found a radiation dose-dependent increase in the percentages of CD25(+)/CD127(-) regulatory T cells in the CD4 T-cell population of the survivors. All these effects of radiation on T-cell immunity resemble effects of aging on the immune system, suggesting that ionizing radiation might direct the T-cell system toward a compromised phenotype and thereby might contribute to an enhanced immunosenescence. Furthermore, there are inverse, significant associations between plasma levels of inflammatory cytokines and the relative number of naïve CD4 T cells, also suggesting that the elevated levels of inflammatory markers found in A-bomb survivors can be ascribed in part to T-cell immunosenescence. We suggest that radiation-induced T-cell immunosenescence may result in activation of inflammatory responses and may be partly involved in the development of aging-associated and inflammation-related diseases frequently observed in A-bomb survivors.

  5. Inflammatory effects of gene transfer into the CNS with defective HSV-1 vectors.

    PubMed

    Wood, M J; Byrnes, A P; Pfaff, D W; Rabkin, S D; Charlton, H M

    1994-09-01

    The use of viral vectors which infect and express genes in post-mitotic neurons is a potential strategy for the treatment of disorders affecting the central nervous system (CNS). However, the inflammatory consequences of such strategies have yet to be systematically examined. Preparations of non-replicating defective herpes simplex virus type 1 (HSV-1) amplicon vectors containing the lacZ gene were obtained by standard methods and stereotaxically injected into the adult rat dentate gyrus (DG). The consequent gene expression and inflammatory effects following microinjection were investigated. beta-Galactosidase activity was detected in neurons of the DG from 24 h to at least 12 days after vector injection. A strong inflammatory response developed within 2 days, characterized by diffuse up-regulation of major histocompatibility complex (MHC) class I antigens and the activation of microglia. After 4 days the recruitment of MHC class II+ cells, activated T lymphocytes and macrophages was detected. These features persisted for at least 31 days. Of importance was the finding of beta-galactosidase activity in a bilateral group of neurons in the supramammillary nuclei (SMN) of the posterior hypothalamus, known to send afferent projections to the DG. The onset of inflammation at this secondary site was delayed, but its cellular characteristics resembled those found at the primary site of injection. Thus, the use of preparations of defective HSV-1 vectors for gene transfer in the CNS has immunological implications both at primary and secondary sites within the CNS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7584093

  6. The family resemblance metaphor: some unfinished business of interpretive inquiry.

    PubMed

    Miller, S I; Fredericks, M

    2000-07-01

    The rapidly expanding discipline of interpretive inquiry, especially in its narrative analysis form, has not been fully cognizant of certain crucial epistemological and methodological assumptions that form the ultimate basis of its purpose. Even after abandoning traditional positivist views, the related disciplines within the human sciences that are engaged in interpretive inquiry have still not discovered the core implicit assumptions that militate against a full acceptance of this form of inquiry. This article outlines the locus of these implicit assumptions and then argues that the legitimacy of these enterprises must be grounded in a well-known but heretofore undiscovered perspective, namely, Wittgenstein's notion of a family resemblance. It is argued that this metaphoric phrase is the key to unlocking the real and unique nature of narrative analysis. PMID:11010071

  7. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    PubMed

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man.

  8. Associations between dietary inflammatory index and inflammatory markers in the Asklepios Study.

    PubMed

    Shivappa, Nitin; Hébert, James R; Rietzschel, Ernst R; De Buyzere, Marc L; Langlois, Michel; Debruyne, Evi; Marcos, Ascensión; Huybrechts, Inge

    2015-02-28

    Previous research has shown that nutrients and certain food items influence inflammation. However, little is known about the associations between diet, as a whole, and inflammatory markers. In the present study, we examined the ability of a FFQ-derived dietary inflammatory index (DII) to predict inflammation. Data from a Belgian cross-sectional study of 2524 generally healthy subjects (age 35-55 years) were used. The DII is a population-based, literature-derived dietary index that was developed to predict inflammation and inflammation-related chronic diseases. The DII was calculated from FFQ-derived dietary information and tested against inflammatory markers, namely C-reactive protein (CRP), IL-6, homocysteine and fibrinogen. Analyses were performed using multivariable logistic regression, adjusting for energy, age, sex, BMI, smoking status, education level, use of non-steroidal anti-inflammatory drugs, blood pressure, use of oral contraceptives, anti-hypertensive therapy, lipid-lowering drugs and physical activity. Multivariable analyses showed significant positive associations between the DII and the inflammatory markers IL-6 (>1·6 pg/ml) (OR 1·19, 95 % CI 1·04, 1·36) and homocysteine (>15 μmol/l) (OR 1·56, 95 % CI 1·25, 1·94). No significant associations were observed between the DII and the inflammatory markers CRP and fibrinogen. These results reinforce the fact that diet, as a whole, plays an important role in modifying inflammation. PMID:25639781

  9. Neutrophil-Derived Proteases Escalate Inflammation through Activation of IL-36 Family Cytokines.

    PubMed

    Henry, Conor M; Sullivan, Graeme P; Clancy, Danielle M; Afonina, Inna S; Kulms, Dagmar; Martin, Seamus J

    2016-02-01

    Recent evidence has strongly implicated the IL-1 family cytokines IL-36α, IL-36β, and IL-36γ as key initiators of skin inflammation. Similar to the other members of the IL-1 family, IL-36 cytokines are expressed as inactive precursors and require proteolytic processing for activation; however, the responsible proteases are unknown. Here, we show that IL-36α, IL-36β, and IL-36γ are activated differentially by the neutrophil granule-derived proteases cathepsin G, elastase, and proteinase-3, increasing their biological activity ~500-fold. Active IL-36 promoted a strong pro-inflammatory signature in primary keratinocytes and was sufficient to perturb skin differentiation in a reconstituted 3D human skin model, producing features resembling psoriasis. Furthermore, skin eluates from psoriasis patients displayed significantly elevated cathepsin G-like activity that was sufficient to activate IL-36β. These data identify neutrophil granule proteases as potent IL-36-activating enzymes, adding to our understanding of how neutrophils escalate inflammatory reactions. Inhibition of neutrophil-derived proteases may therefore have therapeutic benefits in psoriasis. PMID:26776523

  10. Roles for Inflammation and Regulatory T Cells in Colon Cancer

    PubMed Central

    Erdman, Susan E.; Poutahidis, Theofilos

    2014-01-01

    Risk for developing cancer rises substantially as a result of poorly regulated inflammatory responses to pathogenic bacterial infections. Anti-inflammatory CD4+ regulatory cells (TREG) function to restore immune homeostasis during chronic inflammatory disorders. It seems logical that TREG cells would function to reduce risk of inflammation-associated cancer in the bowel by down-regulating inflammation. It is widely believed, however, that TREG function in cancer mainly to suppress protective anticancer inflammatory responses. Thus roles for inflammation, TREG cells, and gut bacteria in cancer are paradoxical and are the subject of controversy. Our accumulated data build upon the “hygiene hypothesis” model in which gastrointestinal (GI) infections lead to changes in TREG that reduce inflammation-associated diseases. Ability of TREG to inhibit or suppress cancer depends upon gut bacteria and IL-10, which serve to maintain immune balance and a protective anti-inflammatory TREG phenotype. However, under poorly regulated pro-inflammatory conditions, TREG fail to inhibit and may instead contribute to a T helper (Th)-17-driven procarcinogenic process, a cancer state that is reversible by down-regulation of inflammation and interleukin (IL)-6. Consequently, hygienic individuals with a weakened IL-10– and TREG–mediated inhibitory loop are highly susceptible to the carcinogenic consequences of elevated inflammation and show more frequent inflammation-associated cancers. Taken together, these data help explain the paradox of inflammation and TREG in cancer and indicate that targeted stimulation of TREG may promote health and significantly reduce risk of cancer. PMID:20019355

  11. Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?

    PubMed

    Siebuhr, A S; Bay-Jensen, A C; Jordan, J M; Kjelgaard-Petersen, C F; Christiansen, C; Abramson, S B; Attur, M; Berenbaum, F; Kraus, V; Karsdal, M A

    2016-01-01

    The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients might benefit from anti-inflammatory treatment is a topic of intense research in the OA field. We have reviewed the current literature on OA, with an emphasis on inflammation in OA, biochemical markers of structural damage, and anti-inflammatory treatments for OA. The literature suggests that the OA patient population is diverse, consisting of several subpopulations, including one associated with inflammation. This inflammatory subpopulation may be identified by a combination of novel serological inflammatory biomarkers. Preliminary evidence from small clinical studies suggests that this subpopulation may benefit from anti-inflammatory treatment currently reserved for other inflammatory arthritides.

  12. Decoding cell death signals in liver inflammation.

    PubMed

    Brenner, Catherine; Galluzzi, Lorenzo; Kepp, Oliver; Kroemer, Guido

    2013-09-01

    Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes.

  13. From Inflammation to Prostate Cancer: The Role of Inflammasomes

    PubMed Central

    Dubey, Seema

    2016-01-01

    Inflammation-associated studies entice specific attention due to inflammation's role in multiple stages of prostate cancer development. However, mechanistic regulation of inflammation inciting prostate cancer remains largely uncharacterized. A focused class of inflammatory regulators known as inflammasomes has recently gained attention in cancer development. Inflammasomes are a multiprotein complex that drives a cascade of proinflammatory cytokines regulating various cellular activities. Inflammasomes activation is linked with infection, stress, or danger signals, which are common events within the prostate gland. In this study, we review the potential of inflammasomes in understanding the role of inflammation in prostate cancer. PMID:27429614

  14. Inflammatory and redox reactions in colorectal carcinogenesis.

    PubMed

    Guina, Tina; Biasi, Fiorella; Calfapietra, Simone; Nano, Mario; Poli, Giuseppe

    2015-03-01

    It has been established that there is a relationship between chronic inflammation and cancer development. The constant colonic inflammation typical of inflammatory bowel diseases is now considered a risk factor for colorectal carcinoma (CRC) development. The inflammatory network of signaling molecules is also required during the late phases of carcinogenesis, to enable cancer cells to survive and to metastasize. Oxidative reactions are an integral part of the inflammatory response, and are generally associated with CRC development. However, when the malignant phenotype is acquired, increased oxidative status induces antioxidant defenses in cancer cells, favoring their aggressiveness. This contradictory behavior of cancer cells toward redox status is of great significance for potential anticancer therapies. This paper summarizes the essential background information relating to the molecules involved in regulating oxidative stress and inflammation during carcinogenesis. Understanding more of their function in CRC stages might provide the foundation for future developments in CRC treatment.

  15. Versican and the Control of Inflammation

    PubMed Central

    Wight, Thomas N.; Kang, Inkyung; Merrilees, Mervyn J.

    2014-01-01

    Versican is an extracellular matrix (ECM) proteoglycan that interacts with cells by binding to non-integrin and integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory cytokines. Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in inflammation. Inflammatory agonists, such as double-stranded RNA mimetics (e.g., poly I:C), stimulate stromal cells, such as smooth muscle cells and fibroblasts, to produce fibrillar ECMs enriched in versican and hyaluronan (HA) that interact with leukocytes promoting their adhesion. Interference with the incorporation of versican into this ECM blocks monocyte adhesion and dampens the inflammatory response. Tumor cells also express elevated levels of versican which interact with myeloid cells to promote an inflammatory response, through stimulating cytokine release, and metastasis. In addition, myeloid cells, such as macrophages in tumors, synthesize versican which affects tumor cell phenotypes, inflammation, and subsequent metastasis. Versican, by binding to hyaluronan, influences T lymphocyte phenotypes and in part controls the ability of these cells to synthesize and secrete cytokines that influence the immune response. Collectively, these studies indicate that versican as an ECM molecule plays a central role in inflammation and as a result it is emerging as a potential target promising wide therapeutic benefits. PMID:24513039

  16. Biology of intracranial aneurysms: role of inflammation

    PubMed Central

    Chalouhi, Nohra; Ali, Muhammad S; Jabbour, Pascal M; Tjoumakaris, Stavropoula I; Gonzalez, L Fernando; Rosenwasser, Robert H; Koch, Walter J; Dumont, Aaron S

    2012-01-01

    Intracranial aneurysms (IAs) linger as a potentially devastating clinical problem. Despite intense investigation, our understanding of the mechanisms leading to aneurysm development, progression and rupture remain incompletely defined. An accumulating body of evidence implicates inflammation as a critical contributor to aneurysm pathogenesis. Intracranial aneurysm formation and progression appear to result from endothelial dysfunction, a mounting inflammatory response, and vascular smooth muscle cell phenotypic modulation producing a pro-inflammatory phenotype. A later final common pathway appears to involve apoptosis of cellular constituents of the vessel wall. These changes result in degradation of the integrity of the vascular wall leading to aneurysmal dilation, progression and eventual rupture in certain aneurysms. Various aspects of the inflammatory response have been investigated as contributors to IA pathogenesis including leukocytes, complement, immunoglobulins, cytokines, and other humoral mediators. Furthermore, gene expression profiling of IA compared with control arteries has prominently featured differential expression of genes involved with immune response/inflammation. Preliminary data suggest that therapies targeting the inflammatory response may have efficacy in the future treatment of IA. Further investigation, however, is necessary to elucidate the precise role of inflammation in IA pathogenesis, which can be exploited to improve the prognosis of patients harboring IA. PMID:22781330

  17. Understanding migraine: Potential role of neurogenic inflammation.

    PubMed

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  18. Understanding migraine: Potential role of neurogenic inflammation

    PubMed Central

    Malhotra, Rakesh

    2016-01-01

    Neurogenic inflammation, a well-defined pathophysiologial process is characterized by the release of potent vasoactive neuropeptides, predominantly calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A from activated peripheral nociceptive sensory nerve terminals (usually C and A delta-fibers). These peptides lead to a cascade of inflammatory tissue responses including arteriolar vasodilation, plasma protein extravasation, and degranulation of mast cells in their peripheral target tissue. Neurogenic inflammatory processes have long been implicated as a possible mechanism involved in the pathophysiology of various human diseases of the nervous system, respiratory system, gastrointestinal tract, urogenital tract, and skin. The recent development of several innovative experimental migraine models has provided evidence suggestive of the involvement of neuropeptides (SP, neurokinin A, and CGRP) in migraine headache. Antidromic stimulation of nociceptive fibers of the trigeminal nerve resulted in a neurogenic inflammatory response with marked increase in plasma protein extravasation from dural blood vessels by the release of various sensory neuropeptides. Several clinically effective abortive antimigraine medications, such as ergots and triptans, have been shown to attenuate the release of neuropeptide and neurogenic plasma protein extravasation. These findings provide support for the validity of using animal models to investigate mechanisms of neurogenic inflammation in migraine. These also further strengthen the notion of migraine being a neuroinflammatory disease. In the clinical context, there is a paucity of knowledge and awareness among physicians regarding the role of neurogenic inflammation in migraine. Improved understanding of the molecular biology, pharmacology, and pathophysiology of neurogenic inflammation may provide the practitioner the context-specific feedback to identify the novel and most effective therapeutic approach to treatment

  19. A case of collagenous gastritis resembling nodular gastritis in endoscopic appearance.

    PubMed

    Tanabe, Jun; Yasumaru, Masakazu; Tsujimoto, Masahiko; Iijima, Hideki; Hiyama, Satoshi; Nishio, Akira; Sasayama, Yoshiaki; Kawai, Naoki; Oshita, Masahide; Abe, Takashi; Kawano, Sunao

    2013-12-01

    A 25-year-old Japanese female was referred to our clinic for the investigation of moderate iron-deficiency anemia and epigastralgia. Endoscopic examination showed diffuse mucosal nodules in the gastric body resembling nodular gastritis, but this pattern was not observed in the antrum. Histology of the gastric biopsies taken from the gastric body showed mild atrophic mucosa with chronic active inflammation. Some of the biopsy specimens showed deposition of patchy, band-like subepithelial collagen. Four years later, the patient showed no clinical symptoms and signs. A follow-up endoscopic examination showed similar findings, which mimicked pseudopolyposis or a cobblestone-like appearance. The biopsy specimens from the depressed mucosa between the nodules revealed a thickened subepithelial collagen band with no improvement, which led to a diagnosis of collagenous gastritis. Treatment with oral administration of proton-pump inhibitors and histamine-2-receptor antagonists had proved ineffective. To make a correct diagnosis of collagenous gastritis, we should determine the characteristic endoscopic findings and take biopsies from the depressed mucosa between the nodules. PMID:26182135

  20. Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model.

    PubMed

    Trøstrup, Hannah; Thomsen, Kim; Christophersen, Lars J; Hougen, Hans P; Bjarnsholt, Thomas; Jensen, Peter Ø; Kirkby, Nikolai; Calum, Henrik; Høiby, Niels; Moser, Claus

    2013-01-01

    Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group (p < 0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p < 0.006). In addition, a higher concentration of interleukin-1beta in the chronic wounds of BALB/c mice was observed at day 7 (p < 0.02), despite a similar number of bacteria in the two mouse strains. The present study succeeded in establishing a chronic PA biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms. In conclusion, our findings indicate that improved infection control of chronic wounds reduces the inflammatory response and may improve healing.

  1. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27.

    PubMed

    Soler, Laura; Miller, Ingrid; Hummel, Karin; Razzazi-Fazeli, Ebrahim; Jessen, Flemming; Escribano, Damian; Niewold, Theo

    2016-05-01

    The growth promoting effect of supplementing animal feed with antibiotics like tetracycline has traditionally been attributed to their antibiotic character. However, more evidence has been accumulated on their direct anti-inflammatory effect during the last two decades. Here we used a pig model to explore the systemic molecular effect of feed supplementation with sub therapeutic levels of oxytetracycline (OTC) by analysis of serum proteome changes. Results showed that OTC promoted growth, coinciding with a significant down regulation of different serum proteins related to inflammation, oxidation and lipid metabolism, confirming the anti-inflammatory mechanism of OTC. Interestingly, apart from the classic acute phase reactants also down regulation was seen of a hibernation associated plasma protein (HP-27), which is to our knowledge the first description in pigs. Although the exact function in non-hibernators is unclear, down regulation of HP-27 could be consistent with increased appetite, which is possibly linked to the anti-inflammatory action of OTC. Given that pigs are good models for human medicine due to their genetic and physiologic resemblance, the present results might also be used for rational intervention in human diseases in which inflammation plays an important role such as obesity, type 2 diabetes and cardiovascular diseases. PMID:26914286

  2. An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn’s disease and experimental colitis in vivo

    PubMed Central

    Stallmach, A; Marth, T; Weiß, B; Wittig, B M; Hombach, A; Schmidt, C; Neurath, M; Zeitz, M; Zeuzem, S; Abken, H

    2004-01-01

    Background and aims: Interleukin-12 (IL-12), a p35/p40 heterodimer, plays a pivotal role in the immune response in Crohn’s disease (CD). Since IL-12 p40 dimers act as IL-12 antagonists, we assayed p40 dimer proteins to modulate chronic intestinal inflammation. Methods: We generated a fusion protein consisting of the IL-12(p40) subunit fused to the constant region of IgG2b. IL-12(p40)-IgG2b was tested in a murine 2,4,6,-trinitrobenzene sulphonic acid (TNBS) colitis model and in lamina propria mononuclear cells (LPMNC) from patients with CD in vitro. Results: Dimeric IL-12(p40)-IgG2b fusion protein bound specifically to the IL-12 receptor. In concentrations <10−7 M, it acted as an IL-12 antagonist as it inhibited interferon γ (IFN-γ) secretion, suppressed proliferation, and increased apoptosis of LPMNC from patients with CD. However, in concentrations >10−6 M, IL-12(p40)-IgG2b increased IFN-γ secretion and lymphocyte proliferation thereby acting as an IL-12 agonist. In TNBS colitic mice, IL-12(p40)-IgG2b decreased mortality (10% v 68%), prevented body weight loss, reduced tumour necrosis factor α, and increased IL-10 secretion. Conclusions: The IL-12(p40)-IgG2b fusion protein has dichotomic properties as a specific IL-12 antagonist and selective repressor of mucosal inflammation at low concentration and as an IL-12 agonist at high concentration. PMID:14960512

  3. Earlobe Inflammation from a Palm Thorn Injury.

    PubMed

    Press, Yan; Peleg, Roni

    2016-05-01

    Injury from the thorn of a palm tree is characterized by a prolonged, painful inflammatory reaction. Even when the source of the inflammation is diagnosed, appropriate treatment is usually delayed because family doctors are not familiar with the entity. Penetration of a palm thorn into the earlobe is an unrecognized cause of local inflammation. We describe a case of injury from a palm tree thorn in this uncommon site. We present the technique of transillumination for the identification and removal of the palm thorn. PMID:26903615

  4. Reparative inflammation takes charge of tissue regeneration.

    PubMed

    Karin, Michael; Clevers, Hans

    2016-01-21

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evolutionarily important process. Recent insights have shed light on the cellular and molecular processes through which conventional inflammatory cytokines and Wnt factors control mammalian tissue repair and regeneration. This is particularly important for regeneration in the gastrointestinal system, especially for intestine and liver tissues in which aberrant and deregulated repair results in severe pathologies.

  5. IAPs, regulators of innate immunity and inflammation.

    PubMed

    Estornes, Yann; Bertrand, Mathieu J M

    2015-03-01

    As indicated by their name, members of the Inhibitor of APoptosis (IAP) family were first believed to be functionally restricted to apoptosis inhibition. It is now clear that IAPs have a much wider spectrum of action, and recent studies even suggest that some of its members primarily regulate inflammatory responses. Inflammation, the first response of the immune system to infection or tissue injury, is highly regulated by ubiquitylation - a posttranslational modification of proteins with various consequences. In this review, we focus on the recently reported functions of XIAP, cIAP1 and cIAP2 as ubiquitin ligases regulating innate immunity and inflammation.

  6. Reparative inflammation takes charge of tissue regeneration.

    PubMed

    Karin, Michael; Clevers, Hans

    2016-01-21

    Inflammation underlies many chronic and degenerative diseases, but it also mitigates infections, clears damaged cells and initiates tissue repair. Many of the mechanisms that link inflammation to damage repair and regeneration in mammals are conserved in lower organisms, indicating that it is an evolutionarily important process. Recent insights have shed light on the cellular and molecular processes through which conventional inflammatory cytokines and Wnt factors control mammalian tissue repair and regeneration. This is particularly important for regeneration in the gastrointestinal system, especially for intestine and liver tissues in which aberrant and deregulated repair results in severe pathologies. PMID:26791721

  7. Angiogenesis in Inflammatory Bowel Disease

    PubMed Central

    Alkim, Canan; Alkim, Huseyin; Koksal, Ali Riza; Boga, Salih; Sen, Ilker

    2015-01-01

    Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. PMID:26839731

  8. Transgenic mice expressing a truncated Peromyscus leucopus TNF-alpha gene manifest an arthritis resembling ankylosing spondylitis.

    PubMed

    Crew, M D; Effros, R B; Walford, R L; Zeller, E; Cheroutre, H; Brahn, E

    1998-04-01

    Several studies have implicated tumor necrosis factor-alpha (TNF-alpha) in autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate further the role of TNF-alpha in inflammatory arthritis, we generated transgenic mice harboring a truncated Peromyscus leucopus TNF-alpha (Pe-TNF) gene. An arthritic phenotype closely resembling human ankylosing spondylitis was observed only in transgenic lines expressing the Pe-TNF transgene at the mRNA level. We characterized the arthritic phenotype in detail by radiographic and histologic techniques. It consisted of severe axial skeletal kyphosis and ankylosis, accompanied by an inflammatory and fibrotic process at the end plates and enthesis. Peripheral joint lesions were absent in mice expressing the P. leucopus TNF-alpha gene, in contrast to the RA-like phenotype described in transgenic mice expressing a truncated human TNF-alpha gene. The Pe-TNF transgenic mouse model provides a unique opportunity to explore potential mechanisms whereby TNF-alpha may initiate an autoimmune arthritis resembling ankylosing spondylitis.

  9. Musculoskeletal Hydatid Cysts Resembling Tumors: A Report of Five Cases.

    PubMed

    Toğral, Güray; Arıkan, Şefik M; Ekiz, Timur; Kekeç, Ahmet F; Ekşioğlu, Mehmet F

    2016-05-01

    Although challenges in treatment of musculoskeletal hydatid cysts (HC) lesions have been documented, data regarding the musculoskeletal HC lesions resembling tumor is scarce. This paper presented 5 patients (3 males, 2 females) with a mean age of 41.6 years with tumor-like lesions of HC. Three of them had left ilium and acetabulum involvement, one involved left femur, and one involved left thigh muscle compartments. Pain was the main symptom and was seen in all patients. Clinical examination, radiologic evaluation, and histologic analysis were performed for diagnosis. Patients were treated through different surgical options, including simple debridement, bone cement filling with or without internal fixation, hip arthrodesis, reconstruction using hemipelvic replantation with femoral prosthesis and distal femur endoprosthetic replacement. After surgery, the operation region was washed by 20% hypertonic saline, and debridement was performed carefully without contamination. All patients received albendazole treatment. Cases were followed up 1 to 9 years for the recurrence. Walking difficulty and pain were the main symptoms during the follow-up. One patient was symptom-free. A reoccurrence in the perioperative soft tissue was detected in only one patient and control visits with antihelmintic treatment were recommended. We would like to emphasize that HC should be kept in mind for the differential diagnosis of the cystic or tumoral lesions of the musculoskeletal system, particularly in the endemic regions. Prompt diagnosis is of paramount importance for preventing destruction and complications. PMID:27384735

  10. CYTOPLASMIC INCLUSIONS RESEMBLING NUCLEOLI IN SYMPATHETIC NEURONS OF ADULT RATS

    PubMed Central

    Grillo, Mary A.

    1970-01-01

    A distinctive cytoplasmic inclusion consisting of a convoluted network of electron-opaque strands embedded in a less dense matrix was identified in the neurons, but not in the supporting cells, of rat sympathetic ganglia. This ball-like structure, designated "nematosome," measures ∼ 0.9 µ and lacks a limiting membrane. Its strands (diameter = 400–600 A) appear to be made of an entanglement of tightly packed filaments and particles ∼ 25–50 A thick. Cytochemical studies carried out with the light microscope suggest the presence of nonhistone proteins and some RNA. Usually only one such structure is present in a cell, and it appears to occur in most ganglion cells. Although they can be seen anywhere in the cell body, nematosomes are typically located in the perinuclear cytoplasm, where they are often associated with smooth-surfaced and coated vesicles. In fine structure and stainability, they bear a resemblance to the fibrous component of the nucleolus. Subsynaptic formations, which are a special feature of some of the synapses in sympathetic ganglia, appear similar to the threadlike elements in the nematosomes. The possibility that these three structures—nucleolus, nematosome, and subsynaptic formation—may be interrelated in origin and function is discussed. PMID:5458990

  11. A neural network dynamics that resembles protein evolution

    NASA Astrophysics Data System (ADS)

    Ferrán, Edgardo A.; Ferrara, Pascual

    1992-06-01

    We use neutral networks to classify proteins according to their sequence similarities. A network composed by 7 × 7 neurons, was trained with the Kohonen unsupervised learning algorithm using, as inputs, matrix patterns derived from the bipeptide composition of cytochrome c proteins belonging to 76 different species. As a result of the training, the network self-organized the activation of its neurons into topologically ordered maps, wherein phylogenetically related sequences were positioned close to each other. The evolution of the topological map during learning, in a representative computational experiment, roughly resembles the way in which one species evolves into several others. For instance, sequences corresponding to vertebrates, initially grouped together into one neuron, were placed in a contiguous zone of the final neural map, with sequences of fishes, amphibia, reptiles, birds and mammals associated to different neurons. Some apparent wrong classifications are due to the fact that some proteins have a greater degree of sequence identity than the one expected by phylogenetics. In the final neural map, each synaptic vector may be considered as the pattern corresponding to the ancestor of all the proteins that are attached to that neuron. Although it may be also tempting to link real time with learning epochs and to use this relationship to calibrate the molecular evolutionary clock, this is not correct because the evolutionary time schedule obtained with the neural network depends highly on the discrete way in which the winner neighborhood is decreased during learning.

  12. On the resemblance of synapse formation and CNS myelination.

    PubMed

    Almeida, R G; Lyons, D A

    2014-09-12

    The myelination of axons in the central nervous system (CNS) is essential for nervous system formation, function and health. CNS myelination continues well into adulthood, but not all axons become myelinated. Unlike the peripheral nervous system, where we know of numerous axon-glial signals required for myelination, we have a poor understanding of the nature or identity of such molecules that regulate which axons are myelinated in the CNS. Recent studies have started to elucidate cell behavior during myelination in vivo and indicate that the choice of which axons are myelinated is made prior to myelin sheath generation. Here we propose that interactions between axons and the exploratory processes of oligodendrocyte precursor cells (OPCs) lead to myelination and may be similar to those between dendrites and axons that prefigure and lead to synapse formation. Indeed axons and OPCs form synapses with striking resemblance to those of neurons, suggesting a similar mode of formation. We discuss families of molecules with specific functions at different stages of synapse formation and address studies that implicate the same factors during axon-OPC synapse formation and myelination. We also address the possibility that the function of such synapses might directly regulate the myelinating behavior of oligodendrocyte processes in vivo. In the future it may be of benefit to consider these similarities when taking a candidate-based approach to dissect mechanisms of CNS myelination.

  13. The role of inflammation in schizophrenia

    PubMed Central

    Müller, Norbert; Weidinger, Elif; Leitner, Bianka; Schwarz, Markus J.

    2015-01-01

    High levels of pro-inflammatory substances such as cytokines have been described in the blood and cerebrospinal fluid of schizophrenia patients. Animal models of schizophrenia show that under certain conditions an immune disturbance during early life, such as an infection-triggered immune activation, might trigger lifelong increased immune reactivity. A large epidemiological study clearly demonstrated that severe infections and autoimmune disorders are risk factors for schizophrenia. Genetic studies have shown a strong signal for schizophrenia on chromosome 6p22.1, in a region related to the human leucocyte antigen (HLA) system and other immune functions. Another line of evidence demonstrates that chronic (dis)stress is associated with immune activation. The vulnerability-stress-inflammation model of schizophrenia includes the contribution of stress on the basis of increased genetic vulnerability for the pathogenesis of schizophrenia, because stress may increase pro-inflammatory cytokines and even contribute to a lasting pro-inflammatory state. Immune alterations influence the dopaminergic, serotonergic, noradrenergic, and glutamatergic neurotransmission. The activated immune system in turn activates the enzyme indoleamine 2,3-dioxygenase (IDO) of the tryptophan/kynurenine metabolism which influences the serotonergic and glutamatergic neurotransmission via neuroactive metabolites such as kynurenic acid. The described loss of central nervous system volume and the activation of microglia, both of which have been clearly demonstrated in neuroimaging studies of schizophrenia patients, match the assumption of a (low level) inflammatory neurotoxic process. Further support for the inflammatory hypothesis comes from the therapeutic benefit of anti-inflammatory medication. Metaanalyses have shown an advantageous effect of cyclo-oxygenase-2 inhibitors in early stages of schizophrenia. Moreover, intrinsic anti-inflammatory, and immunomodulatory effects of antipsychotic drugs

  14. [Inflammatory abdominal aortic aneurysm].

    PubMed

    Ziaja, K; Sedlak, L; Urbanek, T; Kostyra, J; Ludyga, T

    2000-01-01

    The reported incidence of inflammatory abdominal aortic aneurysm (IAAA) is from 2% to 14% of patients with abdominal aortic aneurysm and the etiology of this disease is still discussed--according to the literature several pathogenic theories have been proposed. From 1992 to 1997 32 patients with IAAA were operated on. The patients were mostly symptomatic--abdominal pain was present in 68.75% cases, back pain in 31.25%, fever in 12.5% and weight loss in 6.25% of the operated patients. In all the patients ultrasound examination was performed, in 4 patients CT and in 3 cases urography. All the patients were operated on and characteristic signs of inflammatory abdominal aortic aneurysm like: thickened aortic wall, perianeurysmal infiltration or retroperitoneal fibrosis with involvement of retroperitoneal structures were found. In all cases surgery was performed using transperitoneal approach; in three cases intraoperatively contiguous abdominal organs were injured, which was connected with their involvement into periaortic inflammation. In 4 cases clamping of the aorta was done at the level of the diaphragmatic hiatus. 3 patients (9.37%) died (one patient with ruptured abdominal aortic aneurysm). Authors present diagnostic procedures and the differences in the surgical tactic, emphasizing the necessity of the surgical therapy in patients with inflammatory abdominal aortic aneurysm.

  15. Mouse Model of Cervicovaginal Toxicity and Inflammation for Preclinical Evaluation of Topical Vaginal Microbicides

    PubMed Central

    Catalone, Bradley J.; Kish-Catalone, Tina M.; Budgeon, Lynn R.; Neely, Elizabeth B.; Ferguson, Maelee; Krebs, Fred C.; Howett, Mary K.; Labib, Mohamed; Rando, Robert; Wigdahl, Brian

    2004-01-01

    Clinical trials evaluating the efficacy of nonoxynol-9 (N-9) as a topical microbicide concluded that N-9 offers no in vivo protection against human immunodeficiency virus type 1 (HIV-1) infection, despite demonstrated in vitro inactivation of HIV-1 by N-9. These trials emphasize the need for better model systems to determine candidate microbicide effectiveness and safety in a preclinical setting. To that end, time-dependent in vitro cytotoxicity, as well as in vivo toxicity and inflammation, associated with N-9 exposure were characterized with the goal of validating a mouse model of microbicide toxicity. In vitro studies using submerged cell cultures indicated that human cervical epithelial cells were inherently more sensitive to N-9-mediated damage than human vaginal epithelial cells. These results correlated with in vivo findings obtained by using Swiss Webster mice in which intravaginal inoculation of 1% N-9 or Conceptrol gel (containing 4% N-9) resulted in selective and acute disruption of the cervical columnar epithelial cells 2 h postapplication accompanied by intense inflammatory infiltrates within the lamina propria. Although damage to the cervical epithelium was apparent out to 8 h postapplication, these tissues resembled control tissue by 24 h postapplication. In contrast, minimal damage and infiltration were associated with both short- and long-term exposure of the vaginal mucosa to either N-9 or Conceptrol. These analyses were extended to examine the relative toxicity of polyethylene hexamethylene biguanide (PEHMB), a polybiguanide compound under evaluation as a candidate topical microbicide. In similar studies, in vivo exposure to 1% PEHMB caused minimal damage and inflammation of the genital mucosa, a finding consistent with the demonstration that PEHMB was >350-fold less cytotoxic than N-9 in vitro. Collectively, these studies highlight the murine model of toxicity as a valuable tool for the preclinical assessment of toxicity and inflammation

  16. Resolution Pharmacology: Opportunities for Therapeutic Innovation in Inflammation.

    PubMed

    Perretti, Mauro; Leroy, Xavier; Bland, Elliot J; Montero-Melendez, Trinidad

    2015-11-01

    Current medicines for the clinical management of inflammatory diseases act by inhibiting specific enzymes or antagonising specific receptors or blocking their ligands. In the past decade, a new paradigm in our understanding of the inflammatory process has emerged with the appreciation of genetic, molecular, and cellular mechanisms that are engaged to actively resolve inflammation. The 'resolution of acute inflammation' is enabled by counter-regulatory checkpoints to terminate the inflammatory reaction, promoting healing and repair. It may be possible to harness this knowledge for innovative approaches to the treatment of inflammatory pathologies. Here we discuss current translational attempts to develop agonists at proresolving targets as a strategy to rectify chronic inflammatory status. We reason this new approach will lead to the identification of better drugs that will establish a new branch of pharmacology, 'resolution pharmacology'.

  17. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo.

  18. Anti-inflammatory iridoids of botanical origin.

    PubMed

    Viljoen, A; Mncwangi, N; Vermaak, I

    2012-01-01

    Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo. PMID:22414102

  19. Metabolic Inflammation-Differential Modulation by Dietary Constituents

    PubMed Central

    Lyons, Claire L.; Kennedy, Elaine B.; Roche, Helen M.

    2016-01-01

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin’s action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review. PMID:27128935

  20. Therapeutics targeting persistent inflammation in chronic kidney disease.

    PubMed

    Machowska, Anna; Carrero, Juan Jesus; Lindholm, Bengt; Stenvinkel, Peter

    2016-01-01

    Systemic inflammation is a condition intrinsically linked to chronic kidney disease (CKD) and its other typical sequelae, such as acquired immune dysfunction, protein-energy wasting (PEW), and accelerated vascular aging that promote premature cardiovascular disease (CVD) and infections, the two leading causes of death in CKD patients. Inflammation is a major contributor to complications in CKD, and inflammatory markers, such as C-reactive protein and pro- and anti-inflammatory cytokines, correlate with underlying causes and consequences of the inflamed uremic phenotype, such as oxidative stress, endothelial dysfunction, CVD, PEW, and infections, and are sensitive and independent predictors of outcome in CKD. Therefore, inflammation appears to be a logical target for potential preventive and therapeutic interventions in patients with CKD. Putative anti-inflammatory therapy strategies aiming at preventing complications and improving outcomes in CKD span over several areas: (1) dealing with the source of inflammation (such as cardiovascular, gastrointestinal or periodontal disease and depression); (2) providing nonspecific immune modulatory effects by promoting healthy dietary habits and other lifestyle changes; (3) promoting increased use of recognized pharmacologic interventions that have pleiotropic effects; and, (4) introducing novel targeted anticytokine interventions. This review provides a brief update on inflammatory biomarkers and possible therapeutic approaches targeting inflammation and the uremic inflammatory milieu in patients with CKD. PMID:26173187

  1. Metabolic Inflammation-Differential Modulation by Dietary Constituents.

    PubMed

    Lyons, Claire L; Kennedy, Elaine B; Roche, Helen M

    2016-01-01

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review. PMID:27128935

  2. Therapeutics targeting persistent inflammation in chronic kidney disease.

    PubMed

    Machowska, Anna; Carrero, Juan Jesus; Lindholm, Bengt; Stenvinkel, Peter

    2016-01-01

    Systemic inflammation is a condition intrinsically linked to chronic kidney disease (CKD) and its other typical sequelae, such as acquired immune dysfunction, protein-energy wasting (PEW), and accelerated vascular aging that promote premature cardiovascular disease (CVD) and infections, the two leading causes of death in CKD patients. Inflammation is a major contributor to complications in CKD, and inflammatory markers, such as C-reactive protein and pro- and anti-inflammatory cytokines, correlate with underlying causes and consequences of the inflamed uremic phenotype, such as oxidative stress, endothelial dysfunction, CVD, PEW, and infections, and are sensitive and independent predictors of outcome in CKD. Therefore, inflammation appears to be a logical target for potential preventive and therapeutic interventions in patients with CKD. Putative anti-inflammatory therapy strategies aiming at preventing complications and improving outcomes in CKD span over several areas: (1) dealing with the source of inflammation (such as cardiovascular, gastrointestinal or periodontal disease and depression); (2) providing nonspecific immune modulatory effects by promoting healthy dietary habits and other lifestyle changes; (3) promoting increased use of recognized pharmacologic interventions that have pleiotropic effects; and, (4) introducing novel targeted anticytokine interventions. This review provides a brief update on inflammatory biomarkers and possible therapeutic approaches targeting inflammation and the uremic inflammatory milieu in patients with CKD.

  3. Metabolic Inflammation-Differential Modulation by Dietary Constituents.

    PubMed

    Lyons, Claire L; Kennedy, Elaine B; Roche, Helen M

    2016-04-27

    Obesity arises from a sustained positive energy balance which triggers a pro-inflammatory response, a key contributor to metabolic diseases such as T2D. Recent studies, focused on the emerging area of metabolic-inflammation, highlight that specific metabolites can modulate the functional nature and inflammatory phenotype of immune cells. In obesity, expanding adipose tissue attracts immune cells, creating an inflammatory environment within this fatty acid storage organ. Resident immune cells undergo both a pro-inflammatory and metabolic switch in their function. Inflammatory mediators, such as TNF-α and IL-1β, are induced by saturated fatty acids and disrupt insulin signaling. Conversely, monounsaturated and polyunsaturated fatty acids do not interrupt metabolism and inflammation to the same extent. AMPK links inflammation, metabolism and T2D, with roles to play in all and is influenced negatively by obesity. Lipid spillover results in hepatic lipotoxicity and steatosis. Also in skeletal muscle, excessive FFA can impede insulin's action and promote inflammation. Ectopic fat can also affect pancreatic β-cell function, thereby contributing to insulin resistance. Therapeutics, lifestyle changes, supplements and dietary manipulation are all possible avenues to combat metabolic inflammation and the subsequent insulin resistant state which will be explored in the current review.

  4. Nutritionally Mediated Oxidative Stress and Inflammation

    PubMed Central

    Muñoz, Alexandra; Costa, Max

    2013-01-01

    There are many sources of nutritionally mediated oxidative stress that trigger inflammatory cascades along short and long time frames. These events are primarily mediated via NFκB. On the short-term scale postprandial inflammation is characterized by an increase in circulating levels of IL-6 and TNF-α and is mirrored on the long-term by proinflammatory gene expression changes in the adipocytes and peripheral blood mononuclear cells (PBMCs) of obese individuals. Specifically the upregulation of CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CXCL2/MIP-2α, and CXCL3/MIP-2β is noted because these changes have been observed in both adipocytes and PBMC of obese humans. In comparing numerous human intervention studies it is clear that pro-inflammatory and anti-inflammatory consumption choices mediate gene expression in humans adipocytes and peripheral blood mononuclear cells. Arachidonic acid and saturated fatty acids (SFAs) both demonstrate an ability to increase pro-inflammatory IL-8 along with numerous other inflammatory factors including IL-6, TNFα, IL-1β, and CXCL1 for arachidonic acid and IGB2 and CTSS for SFA. Antioxidant rich foods including olive oil, fruits, and vegetables all demonstrate an ability to lower levels of IL-6 in PBMCs. Thus, dietary choices play a complex role in the mediation of unavoidable oxidative stress and can serve to exacerbate or dampen the level of inflammation. PMID:23844276

  5. Clinical evaluation of proinflammatory cytokine inhibitors (sTNFR I, sTNFR II, IL-1 ra), anti-inflammatory cytokines (IL-10, IL-13) and activation of neutrophils after burn-induced inflammation.

    PubMed

    Sikora, J P; Chlebna-Sokół, D; Andrzejewska, E; Chrul, S; Polakowska, E; Wysocka, A; Sikora, A

    2008-08-01

    The study was aimed at evaluating the involvement of sTNFR I, sTNFR II, IL-1 ra, IL-10, IL-13 and reactive oxygen species (ROS) in systemic inflammatory response syndrome (SIRS) development in severely burned children and at assessing the prognostic value of the immunological markers studied. The study comprised 37 patients (17 burned children and 20 controls). Serum levels of the markers determined by means of ELISA and respiratory burst of neutrophils as well as p55 and p75 tumour necrosis factor-alpha (TNF-alpha) receptor expression using flow cytometry were evaluated twice. The burned children presented significantly higher levels of IL-10 and cytokine inhibitors within the first 6-24 h after injury compared with controls (P < 0.05). The decreased oxygen metabolism of neutrophils and increased TNF-alpha receptor expression were found on admission. Moreover, a significant decrease in initially high sTNFR I, sTNFR II, IL-1 ra, IL-10, IL-13 concentrations (P < 0.05) and reduced expression of TNF-alpha receptors (P < 0.05) were observed after burn therapy, whereas ROS generation evidently augmented (P < 0.05). Four of our children who developed hypovolaemic shock revealed a significantly lower ROS generation and higher concentrations of soluble TNF-alpha receptors and IL-1 ra together with IL-10, IL-13 compared with children with good outcome (P < 0.05). Our results revealed the involvement of both ROS, soluble TNF-alpha receptors and IL-1 ra in the development of SIRS in burned children; their monitoring allows for an assessment of the systemic inflammatory reaction activity. The neutrophil BURSTTEST and IL-1 ra might have been clinically helpful markers of SIRS prognosis.

  6. Tendons – time to revisit inflammation

    PubMed Central

    Rees, Jonathan D; Stride, Matthew; Scott, Alex

    2014-01-01

    It is currently widely accepted among clinicians that chronic tendinopathy is caused by a degenerative process devoid of inflammation. Current treatment strategies are focused on physical treatments, peritendinous or intratendinous injections of blood or blood products and interruption of painful stimuli. Results have been at best, moderately good and at worst a failure. The evidence for non-infammatory degenerative processes alone as the cause of tendinopathy is surprisingly weak. There is convincing evidence that the inflammatory response is a key component of chronic tendinopathy. Newer anti-inflammatory modalities may provide alternative potential opportunities in treating chronic tendinopathies and should be explored further. PMID:23476034

  7. The blessings and curses of intestinal inflammation

    PubMed Central

    Winter, Sebastian E.; Keestra, A. Marijke; Tsolis, Renée M.; Bäumler, Andreas J.

    2010-01-01

    SUMMARY The intestinal immune system has to strike a delicate balance between initiating inflammatory responses against invading bacterial pathogens and avoiding their induction against microbiota colonizing the lumen. Adequate inflammatory responses against bacterial invasion result in the luminal secretion of antimicrobial peptides, as well as the release of cytokines in tissue that recruit and activate phagocytes. However, pathogens have evolved to utilize these environmental changes in the inflamed intestine to promote colonization. This review focuses on the costs and benefits of intestinal inflammation and the fine interplay between the host, its microbiota and enteric pathogens. PMID:20638640

  8. The blessings and curses of intestinal inflammation.

    PubMed

    Winter, Sebastian E; Keestra, A Marijke; Tsolis, Renée M; Bäumler, Andreas J

    2010-07-22

    The intestinal immune system has to strike a delicate balance between initiating inflammatory responses against invading bacterial pathogens and avoiding their induction against microbiota colonizing the lumen. Adequate inflammatory responses against bacterial invasion result in the lumenal secretion of antimicrobial peptides, as well as the release of cytokines in tissue that recruit and activate phagocytes. However, pathogens have evolved to utilize these environmental changes in the inflamed intestine to promote colonization. This review focuses on the costs and benefits of intestinal inflammation and the fine interplay between the host, its microbiota, and enteric pathogens. PMID:20638640

  9. Effects of inflammation on stem cells: together they strive?

    PubMed Central

    Kizil, Caghan; Kyritsis, Nikos; Brand, Michael

    2015-01-01

    Inflammation entails a complex set of defense mechanisms acting in concert to restore the homeostatic balance in organisms after damage or pathogen invasion. This immune response consists of the activity of various immune cells in a highly complex manner. Inflammation is a double-edged sword as it is reported to have both detrimental and beneficial consequences. In this review, we discuss the effects of inflammation on stem cell activity, focusing primarily on neural stem/progenitor cells in mammals and zebrafish. We also give a brief overview of the effects of inflammation on other stem cell compartments, exemplifying the positive and negative role of inflammation on stemness. The majority of the chronic diseases involve an unremitting phase of inflammation due to improper resolution of the initial pro-inflammatory response that impinges on the stem cell behavior. Thus, understanding the mechanisms of crosstalk between the inflammatory milieu and tissue-resident stem cells is an important basis for clinical efforts. Not only is it important to understand the effect of inflammation on stem cell activity for further defining the etiology of the diseases, but also better mechanistic understanding is essential to design regenerative therapies that aim at micromanipulating the inflammatory milieu to offset the negative effects and maximize the beneficial outcomes. PMID:25739812

  10. How corticosteroids control inflammation: Quintiles Prize Lecture 2005

    PubMed Central

    Barnes, Peter J

    2006-01-01

    Corticosteroids are the most effective anti-inflammatory therapy for many chronic inflammatory diseases, such as asthma but are relatively ineffective in other diseases such as chronic obstructive pulmonary disease (COPD). Chronic inflammation is characterised by the increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappaB and activator protein-1, that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, mainly by reversing histone acetylation of activated inflammatory genes through binding of liganded glucocorticoid receptors (GR) to coactivators and recruitment of histone deacetylase-2 (HDAC2) to the activated transcription complex. At higher concentrations of corticosteroids GR homodimers also interact with DNA recognition sites to active transcription of anti-inflammatory genes and to inhibit transcription of several genes linked to corticosteroid side effects. In patients with COPD and severe asthma and in asthmatic patients who smoke HDAC2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of corticosteroids. Theophylline, by activating HDAC, may reverse this corticosteroid resistance. This research may lead to the development of novel anti-inflammatory approaches to manage severe inflammatory diseases. PMID:16604091

  11. How corticosteroids control inflammation: Quintiles Prize Lecture 2005.

    PubMed

    Barnes, Peter J

    2006-06-01

    Corticosteroids are the most effective anti-inflammatory therapy for many chronic inflammatory diseases, such as asthma but are relatively ineffective in other diseases such as chronic obstructive pulmonary disease (COPD). Chronic inflammation is characterised by the increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappaB and activator protein-1, that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, mainly by reversing histone acetylation of activated inflammatory genes through binding of liganded glucocorticoid receptors (GR) to coactivators and recruitment of histone deacetylase-2 (HDAC2) to the activated transcription complex. At higher concentrations of corticosteroids GR homodimers also interact with DNA recognition sites to active transcription of anti-inflammatory genes and to inhibit transcription of several genes linked to corticosteroid side effects. In patients with COPD and severe asthma and in asthmatic patients who smoke HDAC2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of corticosteroids. Theophylline, by activating HDAC, may reverse this corticosteroid resistance. This research may lead to the development of novel anti-inflammatory approaches to manage severe inflammatory diseases.

  12. How corticosteroids control inflammation: Quintiles Prize Lecture 2005.

    PubMed

    Barnes, Peter J

    2006-06-01

    Corticosteroids are the most effective anti-inflammatory therapy for many chronic inflammatory diseases, such as asthma but are relatively ineffective in other diseases such as chronic obstructive pulmonary disease (COPD). Chronic inflammation is characterised by the increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-kappaB and activator protein-1, that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription. Corticosteroids suppress the multiple inflammatory genes that are activated in chronic inflammatory diseases, such as asthma, mainly by reversing histone acetylation of activated inflammatory genes through binding of liganded glucocorticoid receptors (GR) to coactivators and recruitment of histone deacetylase-2 (HDAC2) to the activated transcription complex. At higher concentrations of corticosteroids GR homodimers also interact with DNA recognition sites to active transcription of anti-inflammatory genes and to inhibit transcription of several genes linked to corticosteroid side effects. In patients with COPD and severe asthma and in asthmatic patients who smoke HDAC2 is markedly reduced in activity and expression as a result of oxidative/nitrative stress so that inflammation becomes resistant to the anti-inflammatory actions of corticosteroids. Theophylline, by activating HDAC, may reverse this corticosteroid resistance. This research may lead to the development of novel anti-inflammatory approaches to manage severe inflammatory diseases. PMID:16604091

  13. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

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

    2016-07-01

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

  14. Anti-inflammatory and immunomodulatory properties of Carica papaya.

    PubMed

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

    2016-07-01

    Chronic inflammation is linked with the generation and progression of various diseases such as cancer, diabetes and atherosclerosis, and anti-inflammatory drugs therefore have the potential to assist in the treatment of these conditions. Carica papaya is a tropical plant that is traditionally used in the treatment of various ailments including inflammatory conditions. A literature search was conducted by using the keywords "papaya", "anti-inflammatory and inflammation" and "immunomodulation and immune" along with cross-referencing. Both in vitro and in vivo investigation studies were included. This is a review of all studies published since 2000 on the anti-inflammatory activity of papaya extracts and their effects on various immune-inflammatory mediators. Studies on the anti-inflammatory activities of recognized phytochemicals present in papaya are also included. Although in vitro and in vivo studies have shown that papaya extracts and papaya-associated phytochemicals possess anti-inflammatory and immunomodulatory properties, clinical studies are lacking. PMID:27416522

  15. Stretching Impacts Inflammation Resolution in Connective Tissue.

    PubMed

    Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J; Colas, Romain A; Spite, Matthew; Serhan, Charles N; Langevin, Helene M

    2016-07-01

    Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 min twice daily reduced inflammation and improved pain, 2 weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch versus no stretch for 48 h, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue.

  16. Stretching Impacts Inflammation Resolution in Connective Tissue.

    PubMed

    Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J; Colas, Romain A; Spite, Matthew; Serhan, Charles N; Langevin, Helene M

    2016-07-01

    Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 min twice daily reduced inflammation and improved pain, 2 weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch versus no stretch for 48 h, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

  17. Scrutinizing the mechanisms underlying the induction of anemia of inflammation through GPI-mediated modulation of macrophage activation in a model of African trypanosomiasis.

    PubMed

    Stijlemans, Benoît; Vankrunkelsven, Ann; Brys, Lea; Raes, Geert; Magez, Stefan; De Baetselier, Patrick

    2010-05-01

    In animal trypanosomiasis the severity of infection is reflected by the degree of anemia which resembles anemia of inflammation, involving a skewed iron homeostasis leading to iron accumulation within the reticuloendothelial system. Myeloid cells (M cells) have been implicated in the induction and maintenance of this type of anemia and modulation of M cells through the main trypanosome-derived glycosylphosphatidylinositol (GPI)-anchor could attenuate both anemia and trypano-susceptibility in Trypanosoma brucei-infected mice. Herein the GPI-based treatment, allowing a straightforward comparison between trypanotolerance and susceptibility in T. brucei-infected C57Bl/6 mice, was further adopted to scrutinize mechanisms/pathways underlying trypanosome-elicited anemia. Hereby, the following interlinkable observations were made in GPI-based treated (GBT) T. brucei-infected mice: (i) a reduced inflammatory cytokine production and increased IL-10 production associated with alleviation of anemia and restoration of serum iron levels, (ii) a shift in increased liver expression of iron storage towards iron export genes, (iii) increased erythropoiesis in the bone marrow and extramedullar sites (spleen) probably reflecting a normalized iron homeostasis and availability. Collectively, our results demonstrate that reprogramming macrophages towards an anti-inflammatory state alleviates anemia of inflammation by normalizing iron homeostasis and restoring erythropoiesis.

  18. [Chronic inflammatory bowel diseases in cats].

    PubMed

    Ghermai, A K

    1989-01-01

    The aetiology of chronic idiopathic intestinal inflammation is unknown. It is characterized by a diffuse infiltration with inflammatory cells into the intestinal mucosa and sometimes submucosa. Cats with chronic intermittent vomiting and diarrhoea, later on accompanied by anorexia and weight loss, are presented. Definitive diagnosis can be obtained by intestinal biopsy only. An immune pathogenesis is suspected, which is supported by the fact, that chronic inflammatory bowel disease responds to steroid therapy.

  19. Gait analysis in a mouse model resembling Leigh disease.

    PubMed

    de Haas, Ria; Russel, Frans G; Smeitink, Jan A

    2016-01-01

    Leigh disease (LD) is one of the clinical phenotypes of mitochondrial OXPHOS disorders and also known as sub-acute necrotizing encephalomyelopathy. The disease has an incidence of 1 in 77,000 live births. Symptoms typically begin early in life and prognosis for LD patients is poor. Currently, no clinically effective treatments are available. Suitable animal and cellular models are necessary for the understanding of the neuropathology and the development of successful new therapeutic strategies. In this study we used the Ndufs4 knockout (Ndufs4(-/-)) mouse, a model of mitochondrial complex I deficiency. Ndusf4(-/-) mice exhibit progressive neurodegeneration, which closely resemble the human LD phenotype. When dissecting behavioral abnormalities in animal models it is of great importance to apply translational tools that are clinically relevant. To distinguish gait abnormalities in patients, simple walking tests can be assessed, but in animals this is not easy. This study is the first to demonstrate automated CatWalk gait analysis in the Ndufs4(-/-) mouse model. Marked differences were noted between Ndufs4(-/-) and control mice in dynamic, static, coordination and support parameters. Variation of walking speed was significantly increased in Ndufs4(-/-) mice, suggesting hampered and uncoordinated gait. Furthermore, decreased regularity index, increased base of support and changes in support were noted in the Ndufs4(-/-) mice. Here, we report the ability of the CatWalk system to sensitively assess gait abnormalities in Ndufs4(-/-) mice. This objective gait analysis can be of great value for intervention and drug efficacy studies in animal models for mitochondrial disease.

  20. Ventricular Tachycardia and Resembling Acute Coronary Syndrome During Pheochromocytoma Crisis

    PubMed Central

    Li, Shi-jun; Wang, Tao; Wang, Lin; Pang, Zhan-qi; Ma, Ben; Li, Ya-wen; Yang, Jian; Dong, He

    2016-01-01

    Abstract Pheochromocytomas are neuroendocrine tumors, and its cardiac involvement may include transient myocardial dysfunction, acute coronary syndrome (ACS), and even ventricular arrhythmias. A patient was referred for evaluation of stuttering chest pain, and his electrocardiogram showed T-wave inversion over leads V1 to V4. Coronary angiography showed 90% stenosis in the mid-left anterior descending coronary artery (LAD), which was stented. Five days later, the patient had ventricular tachycardia, and severe hypertension, remarkable blood pressure fluctuation between 224/76 and 70/50 mm Hg. The patient felt abdominal pain and his abdominal ultrasound showed suspicious right adrenal gland tumor. Enhanced computed tomography of adrenal gland conformed that there was a tumor in right adrenal gland accompanied by an upset level of aldosterone. The tumor was removed by laparoscope, and the pathological examination showed pheochromocytoma. After the surgery, the blood pressure turned normal gradually. There was no T-wave inversion in lead V1-V4. Our case illustrates a rare pheochromocytoma presentation with a VT and resembling ACS. In our case, the serious stenosis in the mid of LAD could be explained by worsen the clinical course of myocardial ischemia or severe coronary vasospasm by the excessive amounts of catecholamines released from the tumor. Coronary vasospasm was possible because he had no classic coronary risk factors (e.g. family history and smoking habit, essential hypertension, hyperglycemia and abnormal serum lipoprotein, high body mass index). Thus, pheochromocytoma was missed until he revealed the association of his symptoms with abdominalgia. As phaeochromocytomas that present with cardiovascular complications can be fatal, it is necessary to screen for the disease when patients present with symptoms indicating catecholamine excess. PMID:27057898

  1. Quantitation of corneal inflammation by chemiluminescense.

    PubMed

    Chusid, M J; Shea, M L

    1986-10-01

    Various inflammatory agents, including Pseudomonas aeruginosa, bacterial filtrates, endotoxin, and phorbol myristate acetate were found to induce significant increases in corneal chemiluminescense (CLM). Disruption of polymorphonuclear leukocytes within corneas by sonication, freeze-thawing or cryotherapy, or reduction of corneal infiltration by induction of neutropenia resulted in marked decreases of CLM. Increased corneal CLM was associated with significant increases in corneal thickness and water content. Oxygen-free radical scavengers significantly inhibited CLM of experimentally infected corneas in vitro, as did the anti-inflammatory agents prednisolone acetate, indomethacin, and salicylic acid. In vivo therapy of infected corneas with prednisolone resulted in significant reductions in corneal CLM, thickness, and water content compared with saline-treated eyes. The CLM assay is a simple technique that allows quantitation of corneal inflammation and evaluation of the effect of therapeutic agents on corneal inflammation. PMID:3094481

  2. Inflammation in intervertebral disc degeneration and regeneration

    PubMed Central

    Molinos, Maria; Almeida, Catarina R.; Caldeira, Joana; Cunha, Carla; Gonçalves, Raquel M.; Barbosa, Mário A.

    2015-01-01

    Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players. PMID:25673296

  3. Inflammatory process in Alzheimer's Disease

    PubMed Central

    Meraz-Ríos, Marco A.; Toral-Rios, Danira; Franco-Bocanegra, Diana; Villeda-Hernández, Juana; Campos-Peña, Victoria

    2013-01-01

    Alzheimer Disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence of two major hallmarks, the intracellular neurofibrillary tangles (NFTs) and extracellular neuritic plaques (NPs) surrounded by activated astrocytes and microglia. NFTs consist of paired helical filaments of truncated tau protein that is abnormally hyperphosphorylated. The main component in the NP is the amyloid-β peptide (Aβ), a small fragment of 40–42 amino acids with a molecular weight of 4 kD. It has been proposed that the amyloid aggregates and microglia activation are able to favor the neurodegenerative process observed in AD patients. However, the role of inflammation in AD is controversial, because in early stages the inflammation could have a beneficial role in the pathology, since it has been thought that the microglia and astrocytes activated could be involved in Aβ clearance. Nevertheless the chronic activation of the microglia has been related with an increase of Aβ and possibly with tau phosphorylation. Studies in AD brains have shown an upregulation of complement molecules, pro-inflammatory cytokines, acute phase reactants and other inflammatory mediators that could contribute with the neurodegenerative process. Clinical trials and animal models with non-steroidal anti-inflammatory drugs (NSAIDs) indicate that these drugs may decrease the risk of developing AD and apparently reduce Aβ deposition. Finally, further studies are needed to determine whether treatment with anti-inflammatory strategies, may decrease the neurodegenerative process that affects these patients. PMID:23964211

  4. A data-driven acute inflammation therapy

    PubMed Central

    2013-01-01

    Acute inflammation is a severe medical condition defined as an inflammatory response of the body to an infection. Its rapid progression requires quick and accurate decisions from clinicians. Inadequate and delayed decisions makes acute inflammation the 10th leading cause of death overall in United States with the estimated cost of treatment about $17 billion annually. However, despite the need, there are limited number of methods that could assist clinicians to determine optimal therapies for acute inflammation. We developed a data-driven method for suggesting optimal therapy by using machine learning model that is learned on historical patients' behaviors. To reduce both the risk of failure and the expense for clinical trials, our method is evaluated on a virtual patients generated by a mathematical model that emulates inflammatory response. In conducted experiments, acute inflammation was handled with two complimentary pro- and anti-inflammatory medications which adequate timing and doses are crucial for the successful outcome. Our experiments show that the dosage regimen assigned with our data-driven method significantly improves the percentage of healthy patients when compared to results by other methods used in clinical practice and found in literature. Our method saved 88% of patients that would otherwise die within a week, while the best method found in literature saved only 73% of patients. At the same time, our method used lower doses of medications than alternatives. In addition, our method achieved better results than alternatives when only incomplete or noisy measurements were available over time as well as it was less affected by therapy delay. The presented results provide strong evidence that models from the artificial intelligence community have a potential for development of personalized treatment strategies for acute inflammation. PMID:24565439

  5. Transcriptional Control of Inflammatory Responses

    PubMed Central

    Smale, Stephen T.; Natoli, Gioacchino

    2014-01-01

    The inflammatory response requires the activation of a complex transcriptional program that is both cell-type- and stimulus-specific and involves the dynamic regulation of hundreds of genes. In the context of an inflamed tissue, extensive changes in gene expression occur in both parenchymal cells and infiltrating cells of the immune system. Recently, basic transcriptional mechanisms that control inflammation have been clarified at a genome scale, particularly in macrophages and conventional dendritic cells. The regulatory logic of distinct groups of inflammatory genes can be explained to some extent by identifiable sequence-encoded features of their chromatin organization, which impact on transcription factor (TF) accessibility and impose different requirements for gene activation. Moreover, it has become apparent that the interplay between TFs activated by inflammatory stimuli and master regulators exerts a crucial role in controlling cell-type-specific transcriptional outputs. PMID:25213094

  6. Psoriasis and intraocular inflammation.

    PubMed

    Knox, D L

    1979-01-01

    Presented in this series were seven men and three women. Ages when seen, ranged from 32 to 68 years (average 54). Psoriasis had begun in childhood in the women and in the late 20's and 30's in the men. Arthritis (ankylosing spondylitis) was present in only one. Their ocular inflammations began from ages 26 to 62 (average 41). The onset of the inflammation was acute iritis in four and in indolent iridocylcitis in six. All but one were bilateral and chronic. The vitreous had heavy debris in nine of the ten patients. The retina was normal in only three. Boggy congestion was present in two with cystoid edema. Patches of edema. fluorescein leaking, depigmentation of both maculae, pars plana exudate, and retinal vessel obliteration to grey-white, shaggy cords was present in at least one of the remaining five patients. Systemic corticosteroid therapy has been used in eight of the ten patients described in this report. Doses no higher than 30 mg of prednisone per day were used to initiate reversal of the inflammatory response. In case 10, knowledge of the sensitivity of the process to steroids led to the successful rapid reversal of a recalcitrant iritis with only 20 mg of prednisone as a first dose and 20 mg per day for less than three weeks. Maintenance corticosteroid therapy ranged from 40 mg of prednisone every other day in case 9, prednisone 12.5 mg one day and 5 mg the next in case 8, to 8 mg of Aristocort or methylprednisolone acetate (M-edrol) daily in cases 1 and 2. In summary, these patients are older, have an indolent onset bilateral uveitis with dense vitreous debris, retinal abnormalites, and are extremely sensitive to systemic corticosteroids. Many of these patients had undergone the series of clinical evaluations known as a "uveitis survey." Many different systemic abnormalities were found and merited treatment which rarely made a difference in their ocular disease, though two improved after infected teeth were treated. Assuming that these ocular diseases

  7. Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation.

    PubMed

    Talbot, Sébastien; Abdulnour, Raja-Elie E; Burkett, Patrick R; Lee, Seungkyu; Cronin, Shane J F; Pascal, Maud A; Laedermann, Cedric; Foster, Simmie L; Tran, Johnathan V; Lai, Nicole; Chiu, Isaac M; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M; Kuchroo, Vijay K; Bean, Bruce P; Levy, Bruce D; Woolf, Clifford J

    2015-07-15

    Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation, we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8(+) sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large-pore ion channels to specifically block nociceptors, substantially reduced ovalbumin- or house-dust-mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce the release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4(+) and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  8. Microbe- and danger-induced inflammation.

    PubMed

    Broggi, Achille; Granucci, Francesca

    2015-02-01

    The ability of the immune system to give rise to an effective response against pathogens while maintaining tolerance towards self-tissues has always been an object of keen interest for immunologist. Over the years, different theories have been proposed to explain if and how the immune system is able to discriminate between self and non-self, including the Infectious Non-self theory from Charles Janeway and Polly Matzinger's Danger theory. Nowadays we know Janeway's theory is largely true, however the immune system does respond to injured, stressed and necrotic cells releasing danger signals (DAMPs) with a potent inflammatory response. To avoid unwanted prolonged autoimmune reactions, though, danger-induced inflammation should be tightly regulated. In the present review we discuss how prototypic DAMPs are able to induce inflammation and the peculiarity of danger-induced inflammation, as opposed to a complete immune response to fight pathogen invasions.

  9. Silencing nociceptor neurons reduces allergic airway inflammation

    PubMed Central

    Talbot, Sébastien; Abdulnour, Raja-Elie E.; Burkett, Patrick R.; Lee, Seungkyu; Cronin, Shane J.F.; Pascal, Maud A.; Laedermann, Cedric; Foster, Simmie L.; Tran, Johnathan V.; Lai, Nicole; Chiu, Isaac M.; Ghasemlou, Nader; DiBiase, Matthew; Roberson, David; Von Hehn, Christian; Agac, Busranour; Haworth, Oliver; Seki, Hiroyuki; Penninger, Josef M.; Kuchroo, Vijay K.; Bean, Bruce P.; Levy, Bruce D.; Woolf, Clifford J.

    2015-01-01

    Summary Lung nociceptors initiate cough and bronchoconstriction. To elucidate if these fibers also contribute to allergic airway inflammation we stimulated lung nociceptors with capsaicin and observed increased neuropeptide release and immune cell infiltration. In contrast, ablating Nav1.8+ sensory neurons or silencing them with QX-314, a charged sodium channel inhibitor that enters via large pore ion channels to specifically block nociceptors, substantially reduced ovalbumin or house dust mite-induced airway inflammation and bronchial hyperresponsiveness. We also discovered that IL-5, a cytokine produced by activated immune cells, acts directly on nociceptors to induce release of vasoactive intestinal peptide (VIP). VIP then stimulates CD4+ and resident innate lymphoid type 2 cells, creating an inflammatory signaling loop that promotes allergic inflammation. Our results indicate that nociceptors amplify pathological adaptive immune responses and that silencing these neurons with QX-314 interrupts this neuro-immune interplay, revealing a potential new therapeutic strategy for asthma. PMID:26119026

  10. Preventative oral methylthioadenosine is anti-inflammatory and reduces DSS-induced colitis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylthioadenosine (MTA) is a precursor of the methionine salvage pathway and has been shown to have anti-inflammatory properties in various models of acute and chronic inflammation. However, the anti-inflammatory properties of MTA in models of intestinal inflammation are not defined. We hypothesiz...

  11. Facial Resemblance to Emotions: Group Differences, Impression Effects, and Race Stereotypes

    PubMed Central

    Zebrowitz, Leslie A.; Kikuchi, Masako; Fellous, Jean-Marc

    2013-01-01

    The authors used connectionist modeling to extend previous research on emotion overgeneralization effects. Study 1 demonstrated that neutral expression male faces objectively resemble angry expressions more than female faces do, female faces objectively resemble surprise expressions more than male faces do, White faces objectively resemble angry expressions more than Black or Korean faces do, and Black faces objectively resemble happy and surprise expressions more than White faces do. Study 2 demonstrated that objective resemblance to emotion expressions influences trait impressions even when statistically controlling possible confounding influences of attractiveness and babyfaceness. It further demonstrated that emotion overgeneralization is moderated by face race and that racial differences in emotion resemblance contribute to White perceivers’ stereotypes of Blacks and Asians. These results suggest that intergroup relations may be strained not only by cultural stereotypes but also by adaptive responses to emotion expressions that are overgeneralized to groups whose faces subtly resemble particular emotions. PMID:20085393

  12. Facial resemblance to emotions: group differences, impression effects, and race stereotypes.

    PubMed

    Zebrowitz, Leslie A; Kikuchi, Masako; Fellous, Jean-Marc

    2010-02-01

    The authors used connectionist modeling to extend previous research on emotion overgeneralization effects. Study 1 demonstrated that neutral expression male faces objectively resemble angry expressions more than female faces do, female faces objectively resemble surprise expressions more than male faces do, White faces objectively resemble angry expressions more than Black or Korean faces do, and Black faces objectively resemble happy and surprise expressions more than White faces do. Study 2 demonstrated that objective resemblance to emotion expressions influences trait impressions even when statistically controlling possible confounding influences of attractiveness and babyfaceness. It further demonstrated that emotion overgeneralization is moderated by face race and that racial differences in emotion resemblance contribute to White perceivers' stereotypes of Blacks and Asians. These results suggest that intergroup relations may be strained not only by cultural stereotypes but also by adaptive responses to emotion expressions that are overgeneralized to groups whose faces subtly resemble particular emotions.

  13. The role of inflammation in suicidal behaviour

    PubMed Central

    Brundin, L; Erhardt, S; Bryleva, EY; Achtyes, ED; Postolache, TT

    2015-01-01

    Objective Over the past decade, clinical data have accumulated showing that inflammation might contribute to the pathophysiology of suicide. To evaluate the associations and to identify the support for pathways linking inflammatory processes with suicidal behaviour, a comprehensive review of the literature was undertaken. Method The search terms ‘cytokine’, ‘risk factors’, ‘kynurenine’, ‘asthma’, ‘allergy’, ‘autoimmunity’, ‘traumatic brain injury’, ‘infection’ along with the terms ‘inflammation’ and ‘suicide’ were entered into PubMed, and a thorough analysis of the publications and their reference lists was performed. Results The effects of inflammation on mood and behaviour could partially be mediated by kynurenine pathway metabolites, modulating neuroinflammation and glutamate neurotransmission. At the same time, the triggers of the inflammatory changes documented in suicidal patients may be attributed to diverse mechanisms such as autoimmunity, neurotropic pathogens, stress or traumatic brain injury. Conclusion Targeting the inflammatory system might provide novel therapeutic approaches as well as potential biomarkers to identify patients at increased risk. For the goal of improved detection and treatment of suicidal individuals to be achieved, we need to develop a detailed understanding of the origin, mechanisms and outcomes of inflammation in suicidal behaviour. PMID:26256862

  14. Congenital muscular dystrophy with inflammation: Diagnostic considerations

    PubMed Central

    Konkay, Kaumudi; Kannan, Meena Angamuthu; Lingappa, Lokesh; Uppin, Megha S.; Challa, Sundaram

    2016-01-01

    Background and Purpose: Muscle biopsy features of congenital muscular dystrophies (CMD) vary from usual dystrophic picture to normal or nonspecific myopathic picture or prominent fibrosis or striking inflammatory infiltrate, which may lead to diagnostic errors. A series of patients of CMD with significant inflammatory infiltrates on muscle biopsy were correlated with laminin α2 deficiency on immunohistochemistry (IHC). Material and Methods: Cryostat sections of muscle biopsies from the patients diagnosed as CMD on clinical and muscle biopsy features from 1996 to 2014 were reviewed with hematoxylin and eosin(H&E), enzyme and immunohistochemistry (IHC) with laminin α2. Muscle biopsies with inflammatory infiltrate were correlated with laminin α2 deficiency. Results: There were 65 patients of CMD, with inflammation on muscle biopsy in 16. IHC with laminin α2 was available in nine patients, of which six showed complete absence along sarcolemma (five presented with floppy infant syndrome and one with delayed motor milestones) and three showed discontinuous, and less intense staining. Conclusions: CMD show variable degrees of inflammation on muscle biopsy. A diagnosis of laminin α2 deficient CMD should be considered in patients of muscular dystrophy with inflammation, in children with hypotonia/delayed motor milestones. PMID:27570388

  15. Inflammation in the Pathogenesis of Lyme Neuroborreliosis

    PubMed Central

    Ramesh, Geeta; Didier, Peter J.; England, John D.; Santana-Gould, Lenay; Doyle-Meyers, Lara A.; Martin, Dale S.; Jacobs, Mary B.; Philipp, Mario T.

    2016-01-01

    Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, affects both peripheral and central nervous systems. We assessed a causal role for inflammation in Lyme neuroborreliosis pathogenesis by evaluating the induced inflammatory changes in the central nervous system, spinal nerves, and dorsal root ganglia (DRG) of rhesus macaques that were inoculated intrathecally with live B. burgdorferi and either treated with dexamethasone or meloxicam (anti-inflammatory drugs) or left untreated. ELISA of cerebrospinal fluid showed significantly elevated levels of IL-6, IL-8, chemokine ligand 2, and CXCL13 and pleocytosis in all infected animals, except dexamethasone-treated animals. Cerebrospinal fluid and central nervous system tissues of infected animals were culture positive for B. burgdorferi regardless of treatment. B. burgdorferi antigen was detected in the DRG and dorsal roots by immunofluorescence staining and confocal microscopy. Histopathology revealed leptomeningitis, vasculitis, and focal inflammation in the central nervous system; necrotizing focal myelitis in the cervical spinal cord; radiculitis; neuritis and demyelination in the spinal roots; and inflammation with neurodegeneration in the DRG that was concomitant with significant neuronal and satellite glial cell apoptosis. These changes were absent in the dexamethasone-treated animals. Electromyography revealed persistent abnormalities in F-wave chronodispersion in nerve roots of a few infected animals; which were absent in dexamethasone-treated animals. These results suggest that inflammation has a causal role in the pathogenesis of acute Lyme neuroborreliosis. PMID:25892509

  16. Inflammation and cancer: advances and new agents.

    PubMed

    Crusz, Shanthini M; Balkwill, Frances R

    2015-10-01

    Tumour-promoting inflammation is considered one of the enabling characteristics of cancer development. Chronic inflammatory disease increases the risk of some cancers, and strong epidemiological evidence exists that NSAIDs, particularly aspirin, are powerful chemopreventive agents. Tumour microenvironments contain many different inflammatory cells and mediators; targeting these factors in genetic, transplantable and inducible murine models of cancer substantially reduces the development, growth and spread of disease. Thus, this complex network of inflammation offers targets for prevention and treatment of malignant disease. Much potential exists in this area for novel cancer prevention and treatment strategies, although clinical research to support targeting of cancer-related inflammation and innate immunity in patients with advanced-stage cancer remains in its infancy. Following the initial successes of immunotherapies that modulate the adaptive immune system, we assert that inflammation and innate immunity are important targets in patients with cancer on the basis of extensive preclinical and epidemiological data. The adaptive immune response is heavily dependent on innate immunity, therefore, inhibiting some of the tumour-promoting immunosuppressive actions of the innate immune system might enhance the potential of immunotherapies that activate a nascent antitumour response. PMID:26122183

  17. Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

    PubMed

    Pietri, Panagiota; Vlachopoulos, Charalambos; Tousoulis, Dimitris

    2015-01-01

    Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

  18. Inflammation and its resolution as determinants of acute coronary syndromes

    PubMed Central

    Libby, Peter; Tabas, Ira; Fredman, Gabrielle; Fisher, Edward

    2014-01-01

    Inflammation contributes to many of the characteristics of plaques implicated in the pathogenesis of acute coronary syndromes (ACS). Moreover, inflammatory pathways not only regulate properties of plaques that precipitate ACS but also modulate the clinical consequences of the thrombotic complications of atherosclerosis. This synthesis will provide an update on the fundamental mechanisms of inflammatory responses that govern ACS, and also highlight the ongoing balance between pro-inflammatory mechanisms and endogenous pathways that can promote the resolution of inflammation. An appreciation of the countervailing mechanisms that modulate inflammation in relation to ACS enriches our fundamental understanding of the pathophysiology of this important manifestation of atherosclerosis. In addition, these insights furnish glimpses into potential novel therapeutic interventions to forestall this ultimate complication of the disease. PMID:24902971

  19. Topical Application of Fingolimod Perturbs Cutaneous Inflammation.

    PubMed

    Sun, Wai Y; Dimasi, David P; Pitman, Melissa R; Zhuang, YiZhong; Heddle, Robert; Pitson, Stuart M; Grimbaldeston, Michele A; Bonder, Claudine S

    2016-05-01

    The prevalence of allergies, including rhinitis, eczema, and anaphylaxis, is rising dramatically worldwide. This increase is especially problematic in children who bear the greatest burden of this rising trend. Increasing evidence identifies neutrophils as primary perpetrators of the more severe and difficult to manage forms of inflammation. A newly recognized mechanism by which neutrophils are recruited during the early phase of histamine-induced inflammation involves the sphingosine kinase (SK)/sphingosine-1-phosphate axis. This study examines whether topical application of fingolimod, an established SK/sphingosine-1-phosphate antagonist already in clinical use to treat multiple sclerosis, may be repurposed to treat cutaneous inflammation. Using two mouse models of ear skin inflammation (histamine- and IgE-mediated passive cutaneous anaphylaxis) we topically applied fingolimod prophylactically, as well as after establishment of the inflammatory response, and examined ear swelling, SK activity, vascular permeability, leukocyte recruitment, and production of proinflammatory mediators. The present study reveals that when applied topically, fingolimod attenuates both immediate and late-phase responses to histamine with reduced extravasation of fluid, SK-1 activity, proinflammatory cytokine and chemokine production, and neutrophil influx and prevents ear swelling. Intravital microscopy demonstrates that histamine-induced neutrophil rolling and adhesion to the postcapillary venules in the mouse ears is significantly attenuated even after 24 h. More importantly, these effects are achievable even once inflammation is established. Translation into humans was also accomplished with epicutaneous application of fingolimod resolving histamine-induced and allergen-induced inflammatory reactions in forearm skin. Overall, this study demonstrates, to our knowledge for the first time, that fingolimod may be repurposed to treat cutaneous inflammation. PMID:27001955

  20. Secretion of SerpinB2 from endothelial cells activated with inflammatory stimuli.

    PubMed

    Boncela, Joanna; Przygodzka, Patrycja; Wyroba, Elzbieta; Papiewska-Pajak, Izabela; Cierniewski, Czeslaw S

    2013-05-01

    Due to the lack of an N-terminal signal peptide, SerpinB2 (plasminogen activator inhibitor type 2) accumulates in cells and only a small percentage of it is secreted. The extracellular concentration of SerpinB2 significantly increases during inflammation. In the present study we investigated the mechanism with which SerpinB2 can be secreted from endothelial cells activated with LPS. We evaluated the intracellular distribution of SerpinB2 by double immunogold labeling followed by a high resolution electron microscopy analysis. We found that SerpinB2 gathers in the vesicular structures and in the endothelial cell periphery. These vesicles stained positive for the trans-Golgi network marker TGN46, which is consistent with their formation by the endoplasmatic reticulum (ER) and Golgi-dependent pathways. SerpinB2 was delivered to the plasma membrane, apparently together with TGN46 in the same vesicles, which after fusion with the membranes released cargo. Secretion of SerpinB2 was partially inhibited by brefeldin A. The secreted SerpinB2 was predominantly in its nonglycosylated 43kDa form as evaluated by Western immunoblotting. Our data suggest that increased expression of SerpinB2 by an inflammatory stimulus is sufficient to generate structures that resemble secretory vesicles. These vesicles may represent the mechanism by which high local concentrations of SerpinB2 are released at inflammation sites from endothelial cells.

  1. Inflammation, glutamate, and glia in depression: a literature review.

    PubMed

    McNally, Leah; Bhagwagar, Zubin; Hannestad, Jonas

    2008-06-01

    Multiple lines of evidence suggest that inflammation and glutamate dysfunction contribute to the pathophysiology of depression. In this review we provide an overview of how these two systems may interact. Excess levels of inflammatory mediators occur in a subgroup of depressed patients. Studies of acute experimental activation of the immune system with endotoxin and of chronic activation during interferon-alpha treatment show that inflammation can cause depression. Peripheral inflammation leads to microglial activation which could interfere with excitatory amino acid metabolism leading to inappropriate glutamate receptor activation. Loss of astroglia, a feature of depression, upsets the balance of anti- and pro-inflammatory mediators and further impairs the removal of excitatory amino acids. Microglia activated by excess inflammation, astroglial loss, and inappropriate glutamate receptor activation ultimately disrupt the delicate balance of neuroprotective versus neurotoxic effects in the brain, potentially leading to depression. PMID:18567974

  2. Inflammatory Bowel Disease

    PubMed Central

    Kaser, Arthur; Zeissig, Sebastian; Blumberg, Richard S.

    2015-01-01

    Insights into inflammatory bowel disease (IBD) are advancing rapidly owing to immunologic investigations of a plethora of animal models of intestinal inflammation, ground-breaking advances in the interrogation of diseases that are inherited as complex genetic traits, and the development of culture-independent methods to define the composition of the intestinal microbiota. These advances are bringing a deeper understanding to the genetically determined interplay between the commensal microbiota, intestinal epithelial cells, and the immune system and the manner in which this interplay might be modified by relevant environmental factors in the pathogenesis of IBD. This review examines these interactions and, where possible, potential lessons from IBD-directed, biologic therapies that may allow for elucidation of pathways that are central to disease pathogenesis in humans. PMID:20192811

  3. Virus-mimetic polyplex particles for systemic and inflammation-specific targeted delivery of large genetic contents.

    PubMed

    Kang, S; Lu, K; Leelawattanachai, J; Hu, X; Park, S; Park, T; Min, I M; Jin, M M

    2013-11-01

    Systemic and target-specific delivery of large genetic contents has been difficult to achieve. Although viruses effortlessly deliver kilobase-long genome into cells, its clinical use has been hindered by serious safety concerns and the mismatch between native tropisms and desired targets. Nonviral vectors, in contrast, are limited by low gene transfer efficiency and inherent cytotoxicity. Here we devised virus-mimetic polyplex particles (VMPs) based on electrostatic self-assembly among polyanionic peptide (PAP), cationic polymer polyethyleneimine (PEI) and nucleic acids. We fused PAP to the engineered ligand-binding domain of integrin αLβ2 to target intercellular adhesion molecule-1 (ICAM-1), an inducible marker of inflammation. Fully assembled VMPs packaged large genetic contents, bound specifically to target molecules, elicited receptor-mediated endocytosis and escaped endosomal pathway, resembling intracellular delivery processes of viruses. Unlike conventional PEI-mediated transfection, molecular interaction-dependent gene delivery of VMPs was unaffected by the presence of serum and achieved higher efficiency without toxicity. By targeting overexpressed ICAM-1, VMPs delivered genes specifically to inflamed endothelial cells and macrophages both in vitro and in vivo. Simplicity and versatility of the platform and inflammation-specific delivery may open up opportunities for multifaceted gene therapy that can be translated into the clinic and treat a broad range of debilitating immune and inflammatory diseases.

  4. Inflammation: depression fans the flames and feasts on the heat.

    PubMed

    Kiecolt-Glaser, Janice K; Derry, Heather M; Fagundes, Christopher P

    2015-11-01

    Depression and inflammation fuel one another. Inflammation plays a key role in depression's pathogenesis for a subset of depressed individuals; depression also primes larger cytokine responses to stressors and pathogens that do not appear to habituate. Accordingly, treatment decisions may be informed by attention to questions of how (pathways) and for whom (predispositions) these links exist, which are the focus of this article. When combined with predisposing factors (moderators such as childhood adversity and obesity), stressors and pathogens can lead to exaggerated or prolonged inflammatory responses. The resulting sickness behaviors (e.g., pain, disturbed sleep), depressive symptoms, and negative health behaviors (e.g., poor diet, a sedentary lifestyle) may act as mediating pathways that lead to further, unrestrained inflammation and depression. Depression, childhood adversity, stressors, and diet can all influence the gut microbiome and promote intestinal permeability, another pathway to enhanced inflammatory responses. Larger, more frequent, or more prolonged inflammatory responses could have negative mental and physical health consequences. In clinical practice, inflammation provides a guide to potential targets for symptom management by signaling responsiveness to certain therapeutic strategies. For example, a theme across research with cytokine antagonists, omega-3 fatty acids, celecoxib, and exercise is that anti-inflammatory interventions have a substantially greater impact on mood in individuals with heightened inflammation. Thus, when inflammation and depression co-occur, treating them in tandem may enhance recovery and reduce the risk of recurrence. The bidirectional links between depression, inflammation, and disease suggest that effective depression treatments could have a far-reaching impact on mood, inflammation, and health.

  5. The anti-inflammatory effect of opioids.

    PubMed

    Gavalas, A; Victoratos, P; Yiangou, M; Hadjipetrou-Kourounakis, L; Rekka, E; Kourounakis, P

    1994-01-01

    The anti-inflammatory activity of two novel opioids PM and PO as well as of pethidine was studied. The mouse paw edema, induced by various phlogistic agents, was significantly inhibited after the administration of opioids, fact that was independent of their antioxidant properties. The anti-inflammatory action of the above opioids was not reversed by naloxone. These results suggest that a variety of complex regulatory activities may be performed by opioid agonists via naloxone-sensitive or naloxone insensitive receptors on inflammatory cells, directly or indirectly by the inhibition of cytokines and mediators involved in inflammation.

  6. Resistin in idiopathic inflammatory myopathies

    PubMed Central

    2012-01-01

    Introduction The purpose of this study was to evaluate and compare the serum levels and local expression of resistin in patients with idiopathic inflammatory myopathies to controls, and to determine the relationship between resistin levels, inflammation and disease activity. Methods Serum resistin levels were determined in 42 patients with inflammatory myopathies and 27 healthy controls. The association among resistin levels, inflammation, global disease activity and muscle strength was examined. The expression of resistin in muscle tissues from patients with inflammatory myopathies and healthy controls was evaluated. Gene expression and protein release from resistin-stimulated muscle and mononuclear cells were assessed. Results In patients with inflammatory myopathies, the serum levels of resistin were significantly higher than those observed in controls (8.53 ± 6.84 vs. 4.54 ± 1.08 ng/ml, P < 0.0001) and correlated with C-reactive protein (CRP) levels (r = 0.328, P = 0.044) and myositis disease activity assessment visual analogue scales (MYOACT) (r = 0.382, P = 0.026). Stronger association was observed between the levels of serum resistin and CRP levels (r = 0.717, P = 0.037) as well as MYOACT (r = 0.798, P = 0.007), and there was a trend towards correlation between serum resistin and myoglobin levels (r = 0.650, P = 0.067) in anti-Jo-1 positive patients. Furthermore, in patients with dermatomyositis, serum resistin levels significantly correlated with MYOACT (r = 0.667, P = 0.001), creatine kinase (r = 0.739, P = 0.001) and myoglobin levels (r = 0.791, P = 0.0003) and showed a trend towards correlation with CRP levels (r = 0.447, P = 0.067). Resistin expression in muscle tissue was significantly higher in patients with inflammatory myopathies compared to controls, and resistin induced the expression of interleukins (IL)-1β and IL-6 and monocyte chemoattractant protein (MCP)-1 in mononuclear cells but not in myocytes. Conclusions The results of this study

  7. Smoking, inflammatory patterns, and postprandial hypertriglyceridemia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Smoking is associated with increased postprandial hypertriglyceridemia (PPT). Inflammation and insulin resistance are potential "drivers" for this phenomenon. We tested whether inflammatory patterns and/or insulin resistance explain the effect of smoking on PPT. Methods: Men and women i...

  8. Inflammation in Tendon Disorders.

    PubMed

    Speed, Cathy

    2016-01-01

    The role of inflammation in tendon disorders has long been a subject of considerable debate. Developments in our understanding of the basic science of inflammation have provided further insight into its potential role in specific forms of tendon disease, and the circumstances that may potentiate this. Such circumstances include excessive mechanical stresses on tendon and the presence of systemic inflammation associated with chronic diseases. In this chapter a brief review of the basic science of inflammation is provided and the influence that it may play on tendons is discussed. PMID:27535263

  9. Inflammation and skin cancer: old pals telling new stories.

    PubMed

    Hensler, Sabine; Mueller, Margareta M

    2013-01-01

    Inflammation and the inflammatory infiltrate essentially contribute to tumor development and progression. For skin cancer, the observation that tumors arise in sites of chronic irritation and inflammation dates back to 1828 and has stimulated a whole field of research. Numerous animal models such as models of UV-induced or chemically induced skin carcinogenesis but also trangenic models support the role of a deregulated inflammation in the development of skin cancer. These models have greatly contributed to our understanding of the multistage process of carcinogenesis and have given important insights in the differences between physiological inflammation in a healing wound and the functional contribution of the deregulated tumor-associated inflammation to skin cancer growth and progression. Data from these models are supported by epidemiological studies that emphasize a connection of inflammatory conditions with the development of melanoma and epithelial skin cancer and give first indications for a beneficial effect of anti-inflammatory treatments in reducing the risk for skin cancer. Consequently, anti-inflammatory drugs might represent a highly interesting approach in the prevention and treatment of skin cancers.

  10. Airway Inflammation and Hypersensitivity Induced by Chronic Smoking

    PubMed Central

    Kou, Yu Ru; Kwong, Kevin; Lee, Lu-Yuan

    2011-01-01

    Airway hypersensitivity, characterized by enhanced excitability of airway sensory nerves, is a prominent pathophysiological feature in patients with airway inflammatory diseases. Although the underlying pathogenic mechanism is not fully understood, chronic airway inflammation is believed to be primarily responsible. Cigarette smoking is known to cause chronic airway inflammation, accompanied by airway hyperresponsiveness. Experimental evidence indicates that enhanced excitability of vagal bronchopulmonary sensory nerves and increased tachykinin synthesis in these nerves resulting from chronic inflammation are important contributing factors to the airway hyperresponsiveness. Multiple inflammatory mediators released from various types of structural and inflammatory cells are involved in the smoking-induced airway inflammation, which is mainly regulated by redox-sensitive signaling pathways and transcription factors. Furthermore, recent studies have reported potent sensitizing and stimulatory effects of these inflammatory mediators such as prostanoids and reactive oxygen species on these sensory nerves. In summary, these studies using cigarette smoking as an experimental approach have identified certain potentially important cell signaling pathways and underlying mechanisms of the airway hypersensitivity induced by chronic airway inflammation. PMID:21397052

  11. Acupuncture to Reduce HIV-Associated Inflammation

    PubMed Central

    Swanson, Barbara; Keithley, Joyce K.; Johnson, Angela; Fogg, Louis; Adeyemi, Oluwatoyin; Sha, Beverly E.; Snell, Kimberly A.

    2015-01-01

    Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n = 12, control group n = 13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations. PMID:25922615

  12. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells

    PubMed Central

    Jin, Rong; Yang, Guojun; Li, Guohong

    2010-01-01

    Inflammation plays an important role in the pathogenesis of ischemic stroke and other forms of ischemic brain injury. Experimentally and clinically, the brain responds to ischemic injury with an acute and prolonged inflammatory process, characterized by rapid activation of resident cells (mainly microglia), production of proinflammatory mediators, and infiltration of various types of inflammatory cells (including neutrophils, different subtypes of T cells, monocyte/macrophages, and other cells) into the ischemic brain tissue. These cellular events collaboratively contribute to ischemic brain injury. Despite intense investigation, there are still numerous controversies concerning the time course of the recruitment of inflammatory cells in the brain and their pathogenic roles in ischemic brain injury. In this review, we provide an overview of the time-dependent recruitment of different inflammatory cells following focal cerebral I/R. We discuss how these cells contribute to ischemic brain injury and highlight certain recent findings and currently unanswered questions about inflammatory cells in the pathophysiology of ischemic stroke. PMID:20130219

  13. The Science of Fatty Acids and Inflammation123

    PubMed Central

    Fritsche, Kevin L

    2015-01-01

    Inflammation is believed to play a central role in many of the chronic diseases that characterize modern society. In the past decade, our understanding of how dietary fats affect our immune system and subsequently our inflammatory status has grown considerably. There are compelling data showing that high-fat meals promote endotoxin [e.g., lipopolysaccharide (LPS)] translocation into the bloodstream, stimulating innate immune cells and leading to a transient postprandial inflammatory response. The nature of this effect is influenced by the amount and type of fat consumed. The role of various dietary constituents, including fats, on gut microflora and subsequent health outcomes in the host is another exciting and novel area of inquiry. The impact of specific fatty acids on inflammation may be central to how dietary fats affect health. Three key fatty acid–inflammation interactions are briefly described. First, the evidence suggests that saturated fatty acids induce inflammation in part by mimicking the actions of LPS. Second, the often-repeated claim that dietary linoleic acid promotes inflammation was not supported in a recent systematic review of the evidence. Third, an explanation is offered for why omega-3 (n–3) polyunsaturated fatty acids are so much less anti-inflammatory in humans than in mice. The article closes with a cautionary tale from the genomic literature that illustrates why extrapolating the results from inflammation studies in mice to humans is problematic. PMID:25979502

  14. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

    PubMed

    You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

    2013-04-01

    Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals. PMID:23494259

  15. Effects of exercise training on chronic inflammation in obesity : current evidence and potential mechanisms.

    PubMed

    You, Tongjian; Arsenis, Nicole C; Disanzo, Beth L; Lamonte, Michael J

    2013-04-01

    Chronic, systemic inflammation is an independent risk factor for several major clinical diseases. In obesity, circulating levels of inflammatory markers are elevated, possibly due to increased production of pro-inflammatory cytokines from several tissues/cells, including macrophages within adipose tissue, vascular endothelial cells and peripheral blood mononuclear cells. Recent evidence supports that adipose tissue hypoxia may be an important mechanism through which enlarged adipose tissue elicits local tissue inflammation and further contributes to systemic inflammation. Current evidence supports that exercise training, such as aerobic and resistance exercise, reduces chronic inflammation, especially in obese individuals with high levels of inflammatory biomarkers undergoing a longer-term intervention. Several studies have reported that this effect is independent of the exercise-induced weight loss. There are several mechanisms through which exercise training reduces chronic inflammation, including its effect on muscle tissue to generate muscle-derived, anti-inflammatory 'myokine', its effect on adipose tissue to improve hypoxia and reduce local adipose tissue inflammation, its effect on endothelial cells to reduce leukocyte adhesion and cytokine production systemically, and its effect on the immune system to lower the number of pro-inflammatory cells and reduce pro-inflammatory cytokine production per cell. Of these potential mechanisms, the effect of exercise training on adipose tissue oxygenation is worth further investigation, as it is very likely that exercise training stimulates adipose tissue angiogenesis and increases blood flow, thereby reducing hypoxia and the associated chronic inflammation in adipose tissue of obese individuals.

  16. Inflammation and its genesis in cystic fibrosis.

    PubMed

    Nichols, David P; Chmiel, James F

    2015-10-01

    The host inflammatory response in cystic fibrosis (CF) lung disease has long been recognized as a central pathological feature and an important therapeutic target. Indeed, many believe that bronchiectasis results largely from the oxidative and proteolytic damage comprised within an exuberant airway inflammatory response that is dominated by neutrophils. In this review, we address the longstanding argument of whether or not the inflammatory response is directly attributable to impairment of the cystic fibrosis transmembrane conductance regulator or only secondary to airway obstruction and chronic bacterial infection and challenge the importance of this distinction in the context of therapy. We also review the centrality of neutrophils in CF lung pathophysiology and highlight more recent data that suggest the importance of other cell types and signaling beyond NF-κB activation. We discuss how protease and redox imbalance are critical factors in CF airway inflammation and end by reviewing some of the more promising therapeutic approaches now under development.

  17. Obesity, inflammation, and the gut microbiota.

    PubMed

    Cox, Amanda J; West, Nicholas P; Cripps, Allan W

    2015-03-01

    As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.

  18. Nouvelle cuisine: platelets served with inflammation.

    PubMed

    Kapur, Rick; Zufferey, Anne; Boilard, Eric; Semple, John W

    2015-06-15

    Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

  19. Inflammation and Pharmacological Treatment in Diabetic Retinopathy

    PubMed Central

    Kaštelan, Snježana; Tomić, Martina; Gverović Antunica, Antonela; Salopek Rabatić, Jasminka; Ljubić, Spomenka

    2013-01-01

    Diabetic retinopathy (DR), the most common microvascular complication of diabetes mellitus, is estimated to be the leading cause of new blindness in the working population of developed countries. Primary interventions such as intensive glycemic control, strict blood pressure regulation, and lipid-modifying therapy as well as local ocular treatment (laser photocoagulation and pars plana vitrectomy) can significantly reduce the risk of retinopathy occurrence and progression. Considering the limitations of current DR treatments development of new therapeutic strategies, it becomes necessary to focus on pharmacological treatment. Currently, there is increasing evidence that inflammatory processes have a considerable role in the pathogenesis of DR with multiple studies showing an association of various systemic as well as local (vitreous and aqueous fluid) inflammatory factors and the progression of DR. Since inflammation is identified as a relevant mechanism, significant effort has been directed to the development of new concepts for the prevention and treatment of DR acting on the inflammatory processes and the use of pharmacological agents with anti-inflammatory effect. Inhibiting the inflammatory pathway could be an appealing treatment option for DR in future practices, and as further prospective randomized clinical trials accumulate data, the role and guidelines of anti-inflammatory pharmacologic treatments will become clearer. PMID:24288441

  20. Ghrelin receptor regulates adipose tissue inflammation in aging

    PubMed Central

    Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

  1. [The role of inflammation in colon cancer pathogenesis].

    PubMed

    Francuz, Tomasz; Czajka-Francuz, Paulina; Cisoń-Jurek, Sylwia; Wojnar, Jerzy

    2016-01-01

    The results of the latest research more and more bind development of neoplasms with the chronic inflammation. Inflammatory process creates microenvironment promoting development of neoplasms; as a result, malignant process start to develop in places, where chronic inflammation proceeds or regeneration of tissues takes place. Inflammatory cells not only create suitable microenvironment for development of neoplasms, but also excrete number of cytokines and growth factors promoting survival of a neoplasmatic cell and avoiding its apoptosis, promoting neoangiogenesis and metastases formation. Moreover, cytokines and other pro-inflammatory factors modulate expression of genes important in cancerogenesis, they also activate NFκB-dependent signaling pathways, which favor neoplasmatic cells to avoid apoptosis. On the other hand, oxidative stress accompanying chronic inflammation may promote mutagenesis, enabling that way the neoplasm development. The same cells and metabolic pathways are engaged in inflammatory and neoplasmatic processes, and development of cancer may be a consequence of loss of control over tissue regeneration during resolution of chronic inflammation. The role of most important cells and metabolic pathways in inflammatory process, which may lead to colon cancer, was discussed in this paper.

  2. Central inflammation and sickness-like behavior induced by the food contaminant deoxynivalenol: a PGE2-independent mechanism.

    PubMed

    Girardet, Clémence; Bonnet, Marion S; Jdir, Rajae; Sadoud, Medhi; Thirion, Sylvie; Tardivel, Catherine; Roux, Julien; Lebrun, Bruno; Mounien, Lourdes; Trouslard, Jérôme; Jean, André; Dallaporta, Michel; Troadec, Jean-Denis

    2011-11-01

    Deoxynivalenol (DON), one of the most abundant trichothecenes found on cereals, has been implicated in mycotoxicoses in both humans and farm animals. Low-dose toxicity is characterized by reduced weight gain, diminished nutritional efficiency, and immunologic effects. The levels and patterns of human food commodity contamination justify that DON consumption constitutes a public health issue. DON stability during processing and cooking explains its large presence in human food. We characterized here DON intoxication by showing that the toxin concomitantly affects feeding behavior, body temperature, and locomotor activity after both per os and central administration. Using c-Fos expression mapping, we identified the neuronal structures activated in response to DON and observed that the pattern of neuronal populations activated by the toxin resembled those induced by inflammatory signals. By real-time PCR, we report the first evidences for a DON-induced central inflammation, attested by the strong upregulation of interleukin-1β, interleukin-6, tumor necrosis factor-α, cyclooxygenase-2, and microsomal prostaglandin synthase-1 (mPGES-1) messenger RNA. However, silencing prostaglandins E2 signaling pathways using mPGES-1 knockout mice, which are resistant to cytokine-induced sickness behavior, did not modify the responses to the toxin. These results reveal that, despite strong similarities, behavioral changes observed after DON intoxication differ from classical sickness behavior evoked by inflammatory cytokines.

  3. Focal brain inflammation and autism.

    PubMed

    Theoharides, Theoharis C; Asadi, Shahrzad; Patel, Arti B

    2013-04-09

    Increasing evidence indicates that brain inflammation is involved in the pathogenesis of neuropsychiatric diseases. Autism spectrum disorders (ASD) are characterized by social and learning disabilities that affect as many as 1/80 children in the USA. There is still no definitive pathogenesis or reliable biomarkers for ASD, thus significantly curtailing the development of effective therapies. Many children with ASD regress at about age 3 years, often after a specific event such as reaction to vaccination, infection, stress or trauma implying some epigenetic triggers, and may constitute a distinct phenotype. ASD children respond disproportionally to stress and are also affected by food and skin allergies. Corticotropin-releasing hormone (CRH) is secreted under stress and together with neurotensin (NT) stimulates mast cells and microglia resulting in focal brain inflammation and neurotoxicity. NT is significantly increased in serum of ASD children along with mitochondrial DNA (mtDNA). NT stimulates mast cell secretion of mtDNA that is misconstrued as an innate pathogen triggering an auto-inflammatory response. The phosphatase and tensin homolog (PTEN) gene mutation, associated with the higher risk of ASD, which leads to hyper-active mammalian target of rapamycin (mTOR) signalling that is crucial for cellular homeostasis. CRH, NT and environmental triggers could hyperstimulate the already activated mTOR, as well as stimulate mast cell and microglia activation and proliferation. The natural flavonoid luteolin inhibits mTOR, mast cells and microglia and could have a significant benefit in ASD.

  4. Homeostasis, Inflammation, and Disease Susceptibility

    PubMed Central

    Kotas, Maya E.; Medzhitov, Ruslan

    2015-01-01

    While modernization has dramatically increased lifespan, it has also witnessed the increasing prevalence of diseases such as obesity, hypertension and type 2 diabetes. Such chronic, acquired diseases result when normal physiologic control goes awry and may thus be viewed as failures of homeostasis. However, while nearly every process in human physiology relies on homeostatic mechanisms for stability, only some have demonstrated vulnerability to dysregulation. Additionally, chronic inflammation is a common accomplice of the diseases of homeostasis, yet the basis for this connection is not fully understood. Here we review the design of homeostatic systems and discuss universal features of control circuits that operate at the cellular, tissue and organismal levels. We suggest a framework for classification of homeostatic signals that is based on different classes of homeostatic variables they report on. Finally, we discuss how adaptability of homeostatic systems with adjustable set points creates vulnerability to dysregulation and disease. This framework highlights the fundamental parallels between homeostatic and inflammatory control mechanisms and provides a new perspective on the physiological origin of inflammation. PMID:25723161

  5. Neuronal damage in brain inflammation.

    PubMed

    Aktas, Orhan; Ullrich, Oliver; Infante-Duarte, Carmen; Nitsch, Robert; Zipp, Frauke

    2007-02-01

    In contrast to traditional textbook paradigms, recent studies indicate neuronal damage in classic neuroinflammatory diseases of the brain, such as multiple sclerosis or meningitis. In these cases, immune cells invade the central nervous system compartments, accompanied by a massive breakdown of the blood-brain barrier and typical changes of the cerebrospinal fluid. On the other hand, inflammation within the central nervous system is a common phenomenon even in classic noninflammatory brain diseases that are characterized by degeneration or trauma of neuronal structures, such as Alzheimer disease, Parkinson disease, or stroke. In these cases, inflammation is a frequent occurrence but displays different, more subtle, patterns compared with, for example, multiple sclerosis. Concepts for directly protecting neurons and axons in neuroinflammatory diseases may improve the outcome of the patients. In parallel, epidemiological and animal experimental evidences, as well as first clinical trials indicate the benefit of immunomodulatory therapies for classic noninflammatory brain diseases. We review the evidence for inflammatory neuronal damage and its clinical impact in the context of these diseases. PMID:17296833

  6. Anti-inflammatory activity of Bacopa monniera in rodents.

    PubMed

    Channa, Shabana; Dar, Ahsana; Anjum, Shazia; Yaqoob, Muhammad; Atta-Ur-Rahman

    2006-03-01

    The ethanol extract of Bacopa monniera (Scrophulariaceae) exhibited marked anti-inflammatory activity against carrageenan-induced paw edema in mice and rats, an acute inflammatory model. To assess the possible mechanism of anti-inflammatory action against carrageenan, the ethanol extract was treated with chemical mediators (histamine, serotonin, bradykinin, prostaglandin E(2) and arachidonic acid)-induced edema in rats. The extract selectively inhibited prostaglandin E(2)-induced inflammation. Thus, it may be inferred that B. monniera possesses significant anti-inflammatory activity that may well be relevant for its effectiveness in the healing of various inflammatory conditions in traditional medicine.

  7. The therapeutic potential of carbon monoxide for inflammatory bowel disease.

    PubMed

    Takagi, Tomohisa; Uchiyama, Kazuhiko; Naito, Yuji

    2015-01-01

    Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, are chronic, relapsing and remitting inflammatory disorders of the intestinal tract. Because the precise pathogenesis of IBD remains unclear, it is important to investigate the pathogenesis of IBD and to evaluate new anti-inflammatory strategies. Recent accumulating evidence has suggested that carbon monoxide (CO) may act as an endogenous defensive gaseous molecule to reduce inflammation and tissue injury in various organ injury models, including intestinal inflammation. Furthermore, exogenous CO administration at low concentrations is protective against intestinal inflammation. These data suggest that CO may be a novel therapeutic molecule in patients with IBD. In this review, we present what is currently known regarding the therapeutic potential of CO in intestinal inflammation.

  8. Medicinal plants used in treatment of inflammatory skin diseases

    PubMed Central

    2013-01-01

    Skin is an organ providing contact with the environment and protecting the human body from unfavourable external factors. Skin inflammation, reflected adversely in its functioning and appearance, also unfavourably affects the psyche, the condition of which is important during treatment of chronic skin diseases. The use of plants in treatment of inflammatory skin diseases results from their influence on different stages of inflammation. The paper presents results of the study regarding the anti-inflammatory activity of the plant raw material related to its influence on skin. The mechanism of action, therapeutic indications and side effects of medicinal plants used for treatment of inflammatory diseases of the skin are described. PMID:24278070

  9. The anti-inflammatory action of nepitrin, a flavonoid.

    PubMed

    Agarwal, O P

    1982-07-01

    The anti-inflammatory efficacy of nepitrin (5,3',4'-trihydroxy-6-methoxy flavone), a flavonoid, was investigated in both acute and chronic models of inflammation in rats. Nepitrin was found to possess significant anti-inflammatory activity in the exudative and proliferative phases of inflammation. This action of nepitrin could be due to its anti-bradykinin and anti-angiotensin action. Nepitrin also possessed anti-pyretic and weak analgesic activity. The study reveals that nepitrin may be useful as an anti-inflammatory and anti-arthritic agent. PMID:6982607

  10. Resolvins and omega three polyunsaturated fatty acids: Clinical implications in inflammatory diseases and cancer

    PubMed Central

    Moro, Kazuki; Nagahashi, Masayuki; Ramanathan, Rajesh; Takabe, Kazuaki; Wakai, Toshifumi

    2016-01-01

    Inflammation is a central process in several disorders and contributes to cancer progression. Inflammation involves a complex cascade of pro-inflammatory and anti-inflammatory signaling events with protein and lipid mediators. Recent advances in lipid detection have revealed the importance of lipid mediators in inflammation. Omega three polyunsaturated fatty acids (ω-3 PUFA) are found naturally in fish oil and have been extensively studied in multiple inflammatory diseases with improved outcomes. Resolvins are thought to be the active metabolites of ω-3 PUFA, and are responsible for facilitating the resolving phase of acute inflammation. Clinically, resolvins have been associated with resolution of acute kidney injury and acute lung injury, micro and macro vascular response to injury, and inhibition of microglia-activated inflammation in neurodegenerative disorders. In addition to inflammatory diseases, ω-3 PUFA and resolvins appear to modulate cancer progression. ω-3 PUFA intake has been associated with reduced inflammation in colorectal cancer, and favorable phenotype in breast cancer. Resolvins offer promising therapeutic potential as they may modulate inflammation with minimal side-effects, in contrast to currently available anti-inflammatory medications. This review describes the roles of ω-3 PUFA and resolvins in the inflammatory cascade, various inflammatory diseases, and specific cancers. Additionally, it will discuss the clinical therapeutic potential of resolvins as targets in inflammatory diseases and cancers. PMID:27458590

  11. Decoding cell death signals in liver inflammation.

    PubMed

    Brenner, Catherine; Galluzzi, Lorenzo; Kepp, Oliver; Kroemer, Guido

    2013-09-01

    Inflammation can be either beneficial or detrimental to the liver, depending on multiple factors. Mild (i.e., limited in intensity and destined to resolve) inflammatory responses have indeed been shown to exert consistent hepatoprotective effects, contributing to tissue repair and promoting the re-establishment of homeostasis. Conversely, excessive (i.e., disproportionate in intensity and permanent) inflammation may induce a massive loss of hepatocytes and hence exacerbate the severity of various hepatic conditions, including ischemia-reperfusion injury, systemic metabolic alterations (e.g., obesity, diabetes, non-alcoholic fatty liver disorders), alcoholic hepatitis, intoxication by xenobiotics and infection, de facto being associated with irreversible liver damage, fibrosis, and carcinogenesis. Both liver-resident cells (e.g., Kupffer cells, hepatic stellate cells, sinusoidal endothelial cells) and cells that are recruited in response to injury (e.g., monocytes, macrophages, dendritic cells, natural killer cells) emit pro-inflammatory signals including - but not limited to - cytokines, chemokines, lipid messengers, and reactive oxygen species that contribute to the apoptotic or necrotic demise of hepatocytes. In turn, dying hepatocytes release damage-associated molecular patterns that-upon binding to evolutionary conserved pattern recognition receptors-activate cells of the innate immune system to further stimulate inflammatory responses, hence establishing a highly hepatotoxic feedforward cycle of inflammation and cell death. In this review, we discuss the cellular and molecular mechanisms that account for the most deleterious effect of hepatic inflammation at the cellular level, that is, the initiation of a massive cell death response among hepatocytes. PMID:23567086

  12. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis.

    PubMed

    Cottle, Denny L; Ursino, Gloria M A; Ip, Sally Chi Ieng; Jones, Lynelle K; Ditommaso, Tia; Hacking, Douglas F; Mangan, Niamh E; Mellett, Natalie A; Henley, Katya J; Sviridov, Dmitri; Nold-Petry, Claudia A; Nold, Marcel F; Meikle, Peter J; Kile, Benjamin T; Smyth, Ian M

    2015-01-15

    Harlequin ichthyosis (HI) is a severe skin disease which leads to neonatal death in ∼50% of cases. It is the result of mutations in ABCA12, a protein that transports lipids required to establish the protective skin barrier needed after birth. To better understand the life-threatening newborn HI phenotype, we analysed the developing epidermis for consequences of lipid dysregulation in mouse models. We observed a pro-inflammatory signature which was characterized by chemokine upregulation in embryonic skin which is distinct from that seen in other types of ichthyosis. Inflammation also persisted in grafted HI skin. To examine the contribution of inflammation to disease development, we overexpressed interleukin-37b to globally suppress fetal inflammation, observing considerable improvements in keratinocyte differentiation. These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity. PMID:25209981

  13. Fetal inhibition of inflammation improves disease phenotypes in harlequin ichthyosis.

    PubMed

    Cottle, Denny L; Ursino, Gloria M A; Ip, Sally Chi Ieng; Jones, Lynelle K; Ditommaso, Tia; Hacking, Douglas F; Mangan, Niamh E; Mellett, Natalie A; Henley, Katya J; Sviridov, Dmitri; Nold-Petry, Claudia A; Nold, Marcel F; Meikle, Peter J; Kile, Benjamin T; Smyth, Ian M

    2015-01-15

    Harlequin ichthyosis (HI) is a severe skin disease which leads to neonatal death in ∼50% of cases. It is the result of mutations in ABCA12, a protein that transports lipids required to establish the protective skin barrier needed after birth. To better understand the life-threatening newborn HI phenotype, we analysed the developing epidermis for consequences of lipid dysregulation in mouse models. We observed a pro-inflammatory signature which was characterized by chemokine upregulation in embryonic skin which is distinct from that seen in other types of ichthyosis. Inflammation also persisted in grafted HI skin. To examine the contribution of inflammation to disease development, we overexpressed interleukin-37b to globally suppress fetal inflammation, observing considerable improvements in keratinocyte differentiation. These studies highlight inflammation as an unexpected contributor to HI disease development in utero, and suggest that inhibiting inflammation may reduce disease severity.

  14. Mutually Supportive Mechanisms of Inflammation and Vascular Remodeling.

    PubMed

    Whiteford, J R; De Rossi, G; Woodfin, A

    2016-01-01

    Chronic inflammation is often accompanied by angiogenesis, the development of new blood vessels from existing ones. This vascular response is a response to chronic hypoxia and/or ischemia, but is also contributory to the progression of disorders including atherosclerosis, arthritis, and tumor growth. Proinflammatory and proangiogenic mediators and signaling pathways form a complex and interrelated network in these conditions, and many factors exert multiple effects. Inflammation drives angiogenesis by direct and indirect mechanisms, promoting endothelial proliferation, migration, and vessel sprouting, but also by mediating extracellular matrix remodeling and release of sequestered growth factors, and recruitment of proangiogenic leukocyte subsets. The role of inflammation in promoting angiogenesis is well documented, but by facilitating greater infiltration of leukocytes and plasma proteins into inflamed tissues, angiogenesis can also propagate chronic inflammation. This review examines the mutually supportive relationship between angiogenesis and inflammation, and considers how these interactions might be exploited to promote resolution of chronic inflammatory or angiogenic disorders. PMID:27572130

  15. Chronic inflammatory systemic diseases

    PubMed Central

    Straub, Rainer H.; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3–8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting—cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  16. Facial resemblance increases the attractiveness of same-sex faces more than other-sex faces.

    PubMed Central

    DeBruine, Lisa M.

    2004-01-01

    Our reactions to facial self-resemblance could reflect either specialized responses to cues of kinship or by-products of the general perceptual mechanisms of face encoding and mere exposure. The adaptive hypothesis predicts differences in reactions to self-resemblance in mating and prosocial contexts, while the by-product hypothesis does not. Using face images that were digitally transformed to resemble participants, I showed that the effects of resemblance on attractiveness judgements depended on both the sex of the judge and the sex of the face being judged: facial resemblance increased attractiveness judgements of same-sex faces more than other-sex faces, despite the use of identical procedures to manipulate resemblance. A control experiment indicated these effects were caused neither by lower resemblance of other-sex faces than same-sex faces, nor by an increased perception of averageness or familiarity of same-sex faces due to prototyping or mere exposure affecting only same-sex faces. The differential impact of self-resemblance on our perception of same-sex and other-sex faces supports the hypothesis that humans use facial resemblance as a cue of kinship. PMID:15451700

  17. Pyknoachondrogenesis: an association of skeletal defects resembling achondrogenesis with generalized bone sclerosis. A new condition?

    PubMed

    Camera, G; Giordano, F; Mastroiacovo, P

    1986-10-01

    A stillborn male with skeletal anomalies resembling achondrogenesis with remarkably sclerotic bones is reported. The term "Pyknoachondrogenesis" is suggested for this hitherto undescribed condition. PMID:3791681

  18. Angiogenesis and inflammation in invasive carcinoma of the breast.

    PubMed Central

    Lee, A H; Happerfield, L C; Bobrow, L G; Millis, R R

    1997-01-01

    AIM: To investigate the relation between angiogenesis and inflammation in invasive carcinoma of the breast. METHODS: Sections from 75 invasive carcinomas of the breast were stained using immunohistochemistry for von Willebrand factor, CD3, CD8, CD45RO, CD45RA, CD20, CD68, and c-erbB-2. Tumour vascularity was assessed by counting vessels in the three most vascular areas, and calculating the average (x 400 magnification, field 0.168 mm2). Each pattern of inflammation was scored semiquantitatively. RESULTS: The main pattern of inflammation was a diffuse infiltrate of macrophages, and to a lesser extent T cells. Perivascular and perilobular clusters of B and T cells were noted at the edge of the carcinomas, but were less prominent than the diffuse inflammation. Diffuse inflammation, particularly macrophages, was associated with high tumour grade, tumour necrosis, large tumour size, and c-erbB-2 expression. Perivascular and perilobular inflammation also increased with tumour grade. Tumour vascularity increased slightly with intensity of diffuse inflammation (Spearman's rank correlation coefficient rs = 0.17, p = 0.08), and was inversely related to perilobular inflammation (rs = -0.23, p = 0.03). CONCLUSIONS: The correlations between inflammation and vascularity were weak in this study (r2 about 0.04) and thus there was no evidence of an important relation. Discrepancies between this and other studies may be resolved by studying expression of angiogenic cytokines and proteolytic enzymes by tumour infiltrating inflammatory cells, and their relation to tumour vascularity. PMID:9301551

  19. Alaskan Husky encephalopathy--a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome).

    PubMed

    Brenner, O; Wakshlag, J J; Summers, B A; de Lahunta, A

    2000-07-01

    The gross and histopathological findings in the brain and spinal cord of five Alaskan Husky dogs with a novel incapacitating and ultimately fatal familial and presumed hereditary neurodegenerative disorder are described. Four dogs presented with neurological deficits before the age of 1 year (7-11 months) and one animal at 2.5 years old. Clinical signs in all dogs were of acute onset and included ataxia, seizures, behavioral abnormalities, blindness, facial hypalgesia and difficulties in prehension of food. In animals allowed to survive, the disease was static but with frequent recurrences. Pathological findings were limited to the central nervous system. Grossly visible bilateral and symmetrical cavitated foci were consistently present in the thalamus with variable extension into the caudal brain stem. Microscopic lesions were more widespread and included foci of bilateral and symmetrical degeneration in the basal nuclei, midbrain, pons and medulla, as well as multifocal lesions at the base of sulci in the cerebral cortex and in the gray matter of cerebellar folia in the ventral vermis. Neuronal loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration were the main histopathological findings. In addition, a population of reactive gemistocytic astrocytes with prominent cytoplasmic vacuolation was noted in the thalamus. Lesions of this nature in this distribution within the neuroaxis have not been reported in dogs. The neuropathological findings resemble Leigh's disease/subacute necrotizing encephalomyelopathy of man. Neuronal sparing in conjunction with apparently transient astrocytic vacuolation point to the possible pathogenetic role of astrocytes in the evolution of these lesions. An inherited metabolic derangement of unknown nature is postulated as the cause of this breed-specific disorder.

  20. Triggers of airway inflammation.

    PubMed

    Kerrebijn, K F

    1986-01-01

    Most asthmatics have hyperresponsive airways. This makes them more sensitive than non-asthmatics to bronchoconstricting environmental exposures which, in their turn, may enhance responsiveness. Airway inflammation is considered to be a key determinant of airway hyperresponsiveness: the fact that chronic airway inflammation in cystic fibrosis does not lead to airway hyperresponsiveness of any importance indicates, however, that the role of airway inflammation is complex and incompletely elucidated. The main inducers of airway inflammation are viral infections, antigens, occupational stimuli and pollutants. Although exercise, airway cooling and hyper- or hypotonic aerosols are potent stimuli of bronchoconstriction, it is questionable if airway inflammation is involved in their mode of action. Each of the above-mentioned stimuli is discussed, with emphasis laid on the relation of symptoms to mechanisms. PMID:3533597

  1. Fruit polyphenols, immunity and inflammation.

    PubMed

    González-Gallego, Javier; García-Mediavilla, M Victoria; Sánchez-Campos, Sonia; Tuñón, María J

    2010-10-01

    Flavonoids are a large class of naturally occurring compounds widely present in fruits, vegetables and beverages derived from plants. These molecules have been reported to possess a wide range of activities in the prevention of common diseases, including CHD, cancer, neurodegenerative diseases, gastrointestinal disorders and others. The effects appear to be related to the various biological/pharmacological activities of flavonoids. A large number of publications suggest immunomodulatory and anti-inflammatory properties of these compounds. However, almost all studies are in vitro studies with limited research on animal models and scarce data from human studies. The majority of in vitro research has been carried out with single flavonoids, generally aglycones, at rather supraphysiological concentrations. Few studies have investigated the anti-inflammatory effects of physiologically attainable flavonoid concentrations in healthy subjects, and more epidemiological studies and prospective randomised trials are still required. This review summarises evidence for the effects of fruit and tea flavonoids and their metabolites in inflammation and immunity. Mechanisms of effect are discussed, including those on enzyme function and regulation of gene and protein expression. Animal work is included, and evidence from epidemiological studies and human intervention trials is reviewed. Biological relevance and functional benefits of the reported effects, such as resistance to infection or exercise performance, are also discussed.

  2. Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: a hypothesis proposal.

    PubMed

    Carrero, Juan Jesús; Stenvinkel, Peter

    2009-12-01

    Because inflammation by now is a "traditional" finding that predicts poor outcome and cardiovascular events in the vast majority of patients with ESRD, it could be argued that inflammatory biomarkers should not longer be considered "novel" risk factors. In this review, we forward the hypothesis that, in addition to putative direct proatherogenic effects, persistent inflammation may serve as a catalyst and, in the toxic uremic milieu, modulate the effects of other concurrent vascular and nutritional risk factors. We discuss some recent observational studies, suggesting that the presence of persistent inflammation magnifies the risk for poor outcome via mechanisms related to self-enhancement of the inflammatory cascade and exacerbation of both the wasting and the vascular calcification processes. Because persistent inflammation may be the silent culprit of other commonly observed pathophysiologic alterations in chronic kidney disease, it is imperative that inflammatory markers be regularly monitored and therapeutic attempts be made to target persistent low-grade inflammation in this patient group.

  3. Inflammation in joint injury and post-traumatic osteoarthritis.

    PubMed

    Lieberthal, J; Sambamurthy, N; Scanzello, C R

    2015-11-01

    Inflammation is a variable feature of osteoarthritis (OA), associated with joint symptoms and progression of disease. Signs of inflammation can be observed in joint fluids and tissues from patients with joint injuries at risk for development of post-traumatic osteoarthritis (PTOA). Furthermore, inflammatory mechanisms are hypothesized to contribute to the risk of OA development and progression after injury. Animal models of PTOA have been instrumental in understanding factors and mechanisms involved in chronic progressive cartilage degradation observed after a predisposing injury. Specific aspects of inflammation observed in humans, including cytokine and chemokine production, synovial reaction, cellular infiltration and inflammatory pathway activation, are also observed in models of PTOA. Many of these models are now being utilized to understand the impact of post-injury inflammatory response on PTOA development and progression, including risk of progressive cartilage degeneration and development of chronic symptoms post-injury. As evidenced from these models, a vigorous inflammatory response occurs very early after joint injury but is then sustained at a lower level at the later phases. This early inflammatory response contributes to the development of PTOA features including cartilage erosion and is potentially modifiable, but specific mediators may also play a role in tissue repair. Although the optimal approach and timing of anti-inflammatory interventions after joint injury are yet to be determined, this body of work should provide hope for the future of disease modification tin PTOA.

  4. Maternal adiponectin controls milk composition to prevent neonatal inflammation.

    PubMed

    Jin, Zixue; Du, Yang; Schwaid, Adam G; Asterholm, Ingrid W; Scherer, Philipp E; Saghatelian, Alan; Wan, Yihong

    2015-04-01

    Adiponectin is an important adipokine. Increasing evidence suggests that altered adiponectin levels are linked with metabolic and inflammatory disorders. Here we report an important yet previously unrecognized function of adiponectin in lactation by which maternal adiponectin determines the inflammatory status in the nursing neonates. Surprisingly, both maternal adiponectin overexpression in the transgenic mice and maternal adiponectin deletion in the knockout mice lead to systemic inflammation in the pups, manifested as transient hair loss. However, distinct mechanisms are involved. Adiponectin deficiency triggers leukocyte infiltration and production of inflammatory cytokines in the lactating mammary gland. In contrast, adiponectin overabundance increases lipid accumulation in the lactating mammary gland, resulting in excessive long-chain saturated fatty acids in milk. Interestingly, in both cases, the inflammation and alopecia in the pups can be rescued by Toll-like receptor (TLR)-2/4 deletion because TLR2/4 double-knockout pups are resistant. Mechanistically, long-chain saturated fatty acid activation of inflammatory genes is TLR2/4 dependent and can be potentiated by proinflammatory cytokines, indicating that the inflammatory stimuli in both scenarios functionally converge by activating the TLR2/4 signaling. Therefore, our findings reveal adiponectin as a dosage-dependent regulator of lactation homeostasis and milk quality that critically controls inflammation in the nursing neonates. Furthermore, these results suggest that inflammatory infantile disorders may result from maternal adiponectin dysregulation that can be treated by TLR2/4 inhibition. PMID:25590242

  5. Novel anti-inflammatory therapies for the treatment of atherosclerosis.

    PubMed

    Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L

    2015-06-01

    The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels.

  6. Inflammation fueling atrial fibrillation substrate: seeking ways to "cool" the heart.

    PubMed

    Giannopoulos, Georgios; Cleman, Michael W; Deftereos, Spyridon

    2014-01-01

    Atrial fibrillation (AF) is the most common chronic arrhythmia and a source of significant morbidity and mortality. Previous studies have identified numerous risk factors for the development of AF, including hypertension, diabetes mellitus and heart failure, which have known pathophysiologic links with inflammatory processes. The importance of inflammation in inducing and perpetuating AF has been highlighted not only by experimental, epidemiological and cohort observational studies, but also by clinical trials providing evidence that inflammatory pathways are involved in AF pathogenesis. Local and systemic measurements of biomarkers and inflammatory mediators, as well as atrial biopsy studies have also given insight as to the purported relationship between this arrhythmia and inflammation. However, the link between inflammation and AF is still poorly defined and several issues remain unresolved. The present review offers an overview of existing evidence supporting the "inflammatory" hypothesis for AF pathophysiology and potential therapeutic means for counteracting this "foul interplay" between arrhythmia and inflammation.

  7. Pain and Inflammatory Bowel Disease

    PubMed Central

    Bielefeldt, Klaus; Davis, Brian; Binion, David G.

    2010-01-01

    Abdominal pain is a common symptom of inflammatory bowel disease (IBD: Crohn’s disease, ulcerative colitis). Pain may arise from different mechanisms, which can include partial blockage and gut distention as well as severe intestinal inflammation. A majority of patients suffering from acute flares of IBD will experience pain, which will typically improve as disease activity decreases. However, a significant percentage of IBD patients continue experiencing symptoms of pain despite resolving inflammation and achieving what appears to be clinical remission. Current evidence suggests that sensory pathways sensitize during inflammation, leading to persistent changes in afferent neurons and central nervous system pain processing. Such persistent pain is not only a simple result of sensory input. Pain processing and even the activation of sensory pathways is modulated by arousal, emotion, and cognitive factors. Considering the high prevalence of iatrogenic as well as essential neuropsychiatric comorbidities including anxiety and depression in IBD patients, these central modulating factors may significantly contribute to the clinical manifestation of chronic pain. The improved understanding of peripheral and central pain mechanisms is leading to new treatment strategies that view pain as a biopsychosocial problem. Thus, improving the underlying inflammation, decreasing the excitability of sensitized afferent pathways, and altering emotional and/or cognitive functions may be required to more effectively address the difficult and disabling disease manifestations. PMID:19130619

  8. Regulation of energy balance by inflammation: common theme in physiology and pathology.

    PubMed

    Wang, Hui; Ye, Jianping

    2015-03-01

    Inflammation regulates energy metabolism in both physiological and pathological conditions. Pro-inflammatory cytokines involves in energy regulation in several conditions, such as obesity, aging (calorie restriction), sports (exercise), and cancer (cachexia). Here, we introduce a view of integrative physiology to understand pro-inflammatory cytokines in the control of energy expenditure. In obesity, chronic inflammation is derived from energy surplus that induces adipose tissue expansion and adipose tissue hypoxia. In addition to the detrimental effect on insulin sensitivity, pro-inflammatory cytokines also stimulate energy expenditure and facilitate adipose tissue remodeling. In caloric restriction (CR), inflammatory status is decreased by low energy intake that results in less energy supply to immune cells to favor energy saving under caloric restriction. During physical exercise, inflammatory status is elevated due to muscle production of pro-inflammatory cytokines, which promote fatty acid mobilization from adipose tissue to meet the muscle energy demand. In cancer cachexia, chronic inflammation is elevated by the immune response in the fight against cancer. The energy expenditure from chronic inflammation contributes to weight loss. Immune tolerant cancer cells gains more nutrients during the inflammation. In these conditions, inflammation coordinates energy distribution and energy demand between tissues. If the body lacks response to the pro-inflammatory cytokines (Inflammation Resistance), the energy metabolism will be impaired leading to an increased risk for obesity. In contrast, super-induction of the inflammation activity leads to weight loss and malnutrition in cancer cachexia. In summary, inflammation is a critical component in the maintenance of energy balance in the body. Literature is reviewed in above fields to support this view.

  9. Preterm Birth, Intrauterine Infection, and Fetal Inflammation

    PubMed Central

    Kemp, Matthew W.

    2014-01-01

    Preterm birth (PTB) (delivery before 37 weeks’ gestation) is a leading cause of neonatal death and disease in industrialized and developing countries alike. Infection (most notably in high-risk deliveries occurring before 28 weeks’ gestation) is hypothesized to initiate an intrauterine inflammatory response that plays a key role in the premature initiation of labor as well as a host of the pathologies associated with prematurity. As such, a better understanding of intrauterine inflammation in pregnancy is critical to our understanding of preterm labor and fetal injury, as well as on-going efforts to prevent PTB. Focusing on the fetal innate immune system responses to intrauterine infection, the present paper will review clinical and experimental studies to discuss the capacity for a fetal contribution to the intrauterine inflammation associated with PTB. Evidence from experimental studies to suggest that the fetus has the capacity to elicit a pro-inflammatory response to intrauterine infection is highlighted, with reference to the contribution of the lung, skin, and gastrointestinal tract. The paper will conclude that pathological intrauterine inflammation is a complex process that is modified by multiple factors including time, type of agonist, host genetics, and tissue. PMID:25520716

  10. Switching Off Key Signaling Survival Molecules to Switch On the Resolution of Inflammation

    PubMed Central

    Perez, Denise Alves; Athayde, Rayssa Maciel; Reis, Alesandra Corte; Teixeira, Mauro Martins; Sousa, Lirlândia Pires; Pinho, Vanessa

    2014-01-01

    Inflammation is a physiological response of the immune system to injury or infection but may become chronic. In general, inflammation is self-limiting and resolves by activating a termination program named resolution of inflammation. It has been argued that unresolved inflammation may be the basis of a variety of chronic inflammatory diseases. Resolution of inflammation is an active process that is fine-tuned by the production of proresolving mediators and the shutdown of intracellular signaling molecules associated with cytokine production and leukocyte survival. Apoptosis of leukocytes (especially granulocytes) is a key element in the resolution of inflammation and several signaling molecules are thought to be involved in this process. Here, we explore key signaling molecules and some mediators that are crucial regulators of leukocyte survival in vivo and that may be targeted for therapeutic purposes in the context of chronic inflammatory diseases. PMID:25136148

  11. PPARγ in Inflammatory Bowel Disease

    PubMed Central

    Annese, Vito; Rogai, Francesca; Settesoldi, Alessia; Bagnoli, Siro

    2012-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is member of a family of nuclear receptors that interacts with nuclear proteins acting as coactivators and corepressors. The colon is a major tissue which expresses PPARγ in epithelial cells and, to a lesser degree, in macrophages and lymphocytes and plays a role in the regulation of intestinal inflammation. Indeed, both natural and synthetic PPARγ ligands have beneficial effects in different models of experimental colitis, with possible implication in the therapy of inflammatory bowel disease (IBD). This paper will specifically focus on potential role of PPARγ in the predisposition and physiopathology of IBD and will analyze its possible role in medical therapy. PMID:22997506

  12. [Inflammation, adipokines and obesity].

    PubMed

    Clément, K; Vignes, S

    2009-09-01

    In obese subjects, there is a "low grade" inflammatory state characterized by the moderate but chronic systemic rise of a panel of molecules (adipokines), which carry out, in addition to pro- or anti-inflammatory actions, several immune or metabolic functions, associated with a macrophagic infiltration in adipose tissue. These two factors provide a better understanding of the pathophysiology of obesity and its potential metabolic, cardiovascular or hepatic complications. A small or even moderate reduction of weight significantly reduces circulating inflammatory markers, modulates adipose tissue profile of inflammatory genes and the risks associated with obesity.

  13. Nutrient-induced inflammation in the intestine

    PubMed Central

    Ji, Yong; Sakata, Yasuhisa; Tso, Patrick

    2015-01-01

    Purpose of review To review our current understanding of the relationship between absorption of nutrients and intestinal inflammatory response. Recent findings There is increasing evidence linking gut local inflammatory events with the intake of nutrients. Our recent studies, using the conscious lymph fistula rat model, demonstrate that fat absorption activates the intestinal mucosal mast cells. This is accompanied by a dramatic increase in the lymphatic release of mast cell mediators including histamine, rat mucosal mast cell protease II (RMCPII), as well as the lipid mediator prostaglandin D2 (PGD2). Clinical studies suggest that increased consumption of animal fat may play a role in the pathogenesis of inflammatory bowel disease. This impact of dietary fat may not be restricted to the gut but may extend to the whole body. There is evidence linking a high-fat diet-induced metabolic syndrome, with a low-grade chronic inflammatory state. In this review, we hope to convince the readers that fat absorption can have far reaching physiological and pathophysiological consequences. Summary Understanding the relationship between nutrient absorption and intestinal inflammation is important. We need a better understanding of the interaction between enterocytes and the intestinal immune cells in nutrient absorption and the gut inflammatory responses. PMID:21587069

  14. Inflammation meets sensitization--an explanation for spontaneous nociceptor activity?

    PubMed

    Rukwied, Roman; Weinkauf, Benjamin; Main, Maurice; Obreja, Otilia; Schmelz, Martin

    2013-12-01

    Anti-nerve growth factor (anti-NGF) treatment is analgesic in chronic inflammatory pain conditions without reducing inflammation. Hypothesizing that ongoing pain induced by inflammatory mediators is increased by long term sensitization of nociceptors, we combined the non-inflammatory NGF-sensitization model with an inflammatory ultraviolet-B (UV-B) model in human volunteers. UV-B irradiation of the skin presensitized with NGF 3 weeks before intensified the pre-existing NGF hyperalgesia during the inflammatory phase of UV-B and caused spontaneous pain in about 70% of the subjects. Pain levels paralleled the intensity of UVB inflammation. Hyperalgesia recorded on a VAS (0-100) was additive after combined NGF/UV-B treatment versus single NGF or UV-B treatment for mechanical impact and tonic heat stimuli, again paralleling the intensity of the UV-B inflammation. In contrast, ratings to tonic mechanical pressure (100 kPa for 10 seconds, peak VAS 58 ± 7 vs VAS 21 ± 5 [NGF] and VAS 12 ± 3 [UV-B]) and pinprick (150 mN for 5 seconds, peak VAS 33 ± 7 vs VAS 10 ± 2 [NGF] and VAS 8 ± 3 [UV-B]) increased in a supra-additive manner. This supra-additive effect faded 24 hours after irradiation, although heat sensitization remained increased. Hyperalgesia and spontaneous pain coexisted in NGF/UV-B treated skin but did not significantly correlate (r < -0.1 at day 1 and r < 0.2 at day 3). We conclude that NGF can sensitize nociceptive endings such that inflammatory mediators may cause sufficient excitation to provoke spontaneous pain. Our results suggest that neuronal sensitization and level of inflammation represent independent therapeutic targets in chronic inflammatory pain conditions. PMID:23933233

  15. Implicit trustworthiness ratings of self-resembling faces activate brain centers involved in reward.

    PubMed

    Platek, Steven M; Krill, Austen L; Wilson, Benjamin

    2009-01-01

    On the basis of Hamilton's (Hamilton, W. D. (1964). The genetical evolution of social behavior I, II. Journal of Theoretical Biology, 7, 17-52) theory of inclusive fitness, self-facial resemblance is hypothesized as a mechanism for self-referent phenotypic matching by which humans can detect kin. To understand the mechanisms underlying pro-sociality toward self-resembling faces, we investigated the neural correlates of implicit trustworthiness ratings for self-resembling f