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Anti-inflammatory Mechanisms (anti-inflammatory + mechanism)
Selected AbstractsTherapeutic Effects and Anti-inflammatory Mechanisms of Heparin on Acute Lung Injury in RabbitsACADEMIC EMERGENCY MEDICINE, Issue 7 2008Meitang Wang MD Abstract Objectives:, The objectives were to investigate the potential beneficial effects and molecular mechanisms of heparin and low-molecular-weight heparin (LMWH) on acute lung injury (ALI). Methods:, Forty-eight rabbits were randomized into four groups: normal control group (Group A), lipopolysaccharide (LPS) group (Group B), LPS + heparin group (Group C), and LPS + LMWH group (Group D). The rabbit ALI model was established by intravenous (IV) injection with LPS. Alveolar,arterial O2 difference (PA-aO2), serum tumor necrosis factor , (TNF-,), circulating p38 mitogen-activated protein kinase (p38 MAPK) levels, lung nuclear factor (NF)-,B levels, and lung dry/wet (D/W) ratio were measured, and the lung injury scores were calculated. Results:, Lipopolysaccharide caused significant increases in PA-aO2, serum TNF-,, expression of p38 MAPK in polymorphonuclear neutrophils (PMNs), the lung injury scores, and nuclear factor-,B (NF-,B) activity in the lung tissue and caused a decrease in lung D/W ratio. A positive linear correlation was found between p38 MAPK and TNF-, at 1, 2, 4, and 6 hours (r = 0.68, 0.92, 0.93, and 0.93, respectively) and between NF-,B and p38 MAPK and TNF-, at 6 hours (r = 0.94 and 0.83, respectively). IV heparin or LMWH given after LPS treatment attenuated these changes in inflammatory response, oxygenation, p38 MAPK expression, and NF-,B activation. Conclusions:, The anti-inflammatory mechanisms of heparin in ALI may be inhibiting p38 MAPK and NF-,B activities, and then TNF-, overexpression, thus alleviating the inflammatory reaction. [source] Fructus Ligustrum lucidi inhibits inflammatory mediator release through inhibition of nuclear factor-,B in mouse peritoneal macrophagesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2007Hyo-Jin An ABSTRACT Fructus Ligustrum lucidi (FLL) is a widely used herbal medicine for the treatment of a variety of pathologies. We have investigated the anti-inflammatory mechanism of FLL in mouse peritoneal macrophages. FLL exerted an anti-inflammatory action through inhibition of lipopolysaccharide (LPS)-induced tumour necrosis factor (TNF)-, production in mouse peritoneal macrophages. The maximal inhibition rate of TNF-, production by FLL (0.5 mg mL,1) was 60.88 + 0.30%. In the inflammatory process, nitric oxide (NO) and prostaglandin E2 (PGE2) increased in peritoneal macrophages. FLL decreased the protein level of NO and PGE2 in LPS-stimulated mouse peritoneal macrophages. In addition, FLL inhibited nuclear factor-,B activation and I,B-, degradation by the decrease in I,B-, phosphorylation. Our study suggested that FLL reduced inflammation via an important molecular mechanism, which might explain its beneficial effect in the regulation of inflammatory reactions. [source] Dietary Cholate Is Required for Antiatherogenic Effects of Ethanol in Mouse ModelsALCOHOLISM, Issue 9 2003Mark A. Deeg Background: Human consumption of moderate amounts of ethanol is associated with reduced cardiovascular events. Studies examining the effect of ethanol on atherosclerosis in mouse models have yielded conflicting results that may be due to differences in dietary fat and cholate content. To determine if dietary cholate influences ethanol's effect on atherosclerosis, we fed apolipoprotein E,/, and low-density lipoprotein receptor (LDLR),/, mice different liquid diets with or without ethanol. Methods: Apolipoprotein E,/, mice were fed a low-fat or high saturated fat, cholate-containing diet with or without ethanol for 3 to 10 weeks, and LDLR,/, mice were fed a low-fat, high saturated fat, or high saturated fat diet with cholate with or without ethanol for 7 weeks. At the end of the feeding study, aortic root lesion size was determined and compared with serum cholesterol, triglycerides, and high-density lipoprotein cholesterol. Because dietary cholate increases hepatic nuclear factor (NF)-,B and ethanol inhibits NF-,B, we also examined the effect of ethanol on aortic NF-,B binding activity. Results: Adding ethanol to a low-fat diet had no effect on lesion size. Similarly, ethanol had no effect on lesion size in LDLR,/, mice consuming a high saturated fat diet. Adding ethanol to a high-fat, cholate-containing diet for either strain resulted in a 25% to 50% reduction in lesion size. Dietary cholate increased and ethanol reduced NF-,B binding activity in the aorta. Conclusions: These results suggest that ethanol inhibits atherosclerosis in the presence of dietary cholate, which may occur via an anti-inflammatory mechanism. [source] The anti-inflammatory mechanism of 635 nm light-emitting-diode irradiation compared with existing COX inhibitorsLASERS IN SURGERY AND MEDICINE, Issue 7 2007Wonbong Lim PhD Abstract Background and Objectives Inhibition of cyclooxygenase (COX) and prostaglandin E2 (PGE2) protects cells against cell injury in specific pathophysiological situations: inflammation and oxidative stress. Although the anti-inflammatory effects have been reported in clinical fields for specific wavelength irradiation during wound healing, the physiological mechanism has not been clarified yet. The aim of the present study is to investigate the anti-inflammatory mechanism of 635 nm light-emitting-diode (LED) irradiation compared with existing COX inhibitors. Study Design/Materials and Methods The present study investigated anti-inflammatory effects of 635 nm irradiation on PGE2 release, COX and phospholipase A2 (PLA2) expression, and reactive oxygen species (ROS) dissociation in arachidonic acid (AA)-treated human gingival fibroblast (hGF). These results were compared with their existing COX inhibitors: indomethacin and ibuprofen. The PGE2 release was measured by enzyme immunoassay, the COX expression was measured by western blot and reverse transcriptase polymerase chain reaction (RT-PCR), and ROS level was measured by flow cytometry, laser scanning confocal microscope and RT-PCR. Results Results showed that 635 nm irradiation and existing COX inhibitors inhibit expression of COX and PGE2 release. Unlike indomethacin and ibuprofen, 635 nm irradiation leads to a decrease of ROS levels and mRNA expression of cytosolic phospholipase A2 (cPLA2) and secretary phospholipase A2 (sPLA2). Conclusion Taken together, 635 nm irradiation, unlike indomethacin and ibuprofen, can directly dissociate the ROS. This inhibits cPLA2, sPLA2, and COX expression, and results in the inhibition of PGE2 release. Thus, we suggest that 635 nm irradiation inhibits PGE2 synthesis like COX inhibitor and appears to be useful as an anti-inflammatory tool. Lesers Surg. Med. 39:614,621, 2007. © 2007 Wiley-Liss, Inc. [source] The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypassCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2008C. Selim Isbir Abstract Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24,h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p,=,0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB. Copyright © 2007 John Wiley & Sons, Ltd. [source] Monitoring of monocyte functional state after extracorporeal circulation: A flow cytometry studyCYTOMETRY, Issue 1 2004Silverio Sbrana Abstract Background Cardiovascular surgery with cardiopulmonary bypass (CPB) induces systemic inflammation and postoperative complications depending on pro- and anti-inflammatory mechanisms. Activated polymorphonuclear cells and monocytes may be responsible for morbidity associated with CPB. Knowledge of the monocyte functional state in particular may help to develop protective interventions. Methods Samples were drawn from venous peripheral blood (basal condition, at 4 and 24 h after CPB) and coronary blood (before and after cardioplegic arrest) of 14 patients undergoing cardiac surgery. The following phenotypic and functional parameters of the monocyte population were studied by flow cytometry: surface molecules expression (CD18, CD11a, CD11b, CD14, CD15, CD45, HLA-DR, and Toll-like receptor [TLR]-4), myeloperoxidase (MPO) content, and intracellular cytokine production (tumor necrosis factor [TNF]-,, interleukin [IL]-1,, IL-6, and IL-8). Results Cardiac surgery with CPB induced down-modulation of surface molecules expression on peripheral monocytes, especially at 24 h after CPB, for CD18, CD11a, and CD11b (P < 0.003) and for the CD15 adhesive cluster (P = 0.0028) and HLA-DR (P < 0.001). At 4 h after CPB, downregulation was observed for CD14 (P = 0.004), CD45 (P = 0.014), and CD15 (P = 0.0056). A loss of MPO was detected in venous peripheral (at 24 h after CPB, P = 0.01) or coronary (at reperfusion, P < 0.02) blood. The CD15 cluster complex exhibited a down-modulation in coronary blood (at reperfusion, P = 0.0003). Spontaneous intracellular production of IL-1,, IL-6, and IL-8 decreased at 24 h after CPB (P < 0.05). Conclusions The down-modulation of integrins and adhesive receptor expression and the loss of MPO suggest a strong activation and shedding reaction of circulating monocyte after CPB, further exacerbated by contact with coronary ischemic vessels. The changes of differentiation antigens may reflect the appearance of a partially immature population immediately after CPB. The reduced proinflammatory cytokine production, observed at 24 h after CPB, suggests a functional polarization of circulating monocytes. © 2003 Wiley-Liss, Inc. [source] Expression profiling of IL-10-regulated genes in human monocytes and peripheral blood mononuclear cells from psoriatic patients during IL-10 therapyEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2004Mechthild Jung Abstract Interleukin-10 (IL-10), originally identified as an inhibitor of pro-inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL-10 functions. We aimed at identifying possiblemediators of in vitro IL-10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with,12,000 genes. To prove relevance of the identified genes for the clinicalsituation we compared these in vitro results with genes being regulated by IL-10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL-10 therapy. A high proportion of the 1,600,genes up-regulated and 1,300 genes down-regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL-10, can be assigned to known IL-10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL-10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up-regulation of heme oxygenase-1 (HO-1). However, we demonstrate that the anti-inflammatory mechanisms of IL-10 remain functional even when HO-1 is irreversibly inhibited. [source] Neuroprotective effects of human mesenchymal stem cells on dopaminergic neurons through anti-inflammatory action,GLIA, Issue 1 2009You-Joung Kim Abstract Parkinson's disease (PD) is a common, progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra (SN). Numerous studies have provided evidence suggesting that neuroinflammation plays an important role in the pathogenesis of PD. In this study, we used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation models to investigate whether human mesenchymal stem cells (hMSCs) have a protective effect on the dopaminergic system through anti-inflammatory mechanisms. The hMSC treatment significantly decreased LPS-induced microglial activation, tumor necrosis factor (TNF)-,, inducible nitric oxide synthase (iNOS) mRNA expression, and production of NO and TNF-, compared with the LPS-only treatment group. In co-cultures of microglia and mesencephalic dopaminergic neurons, hMSC treatment significantly decreased the loss of tyrosine hydroxylase-immunopositive (TH-ip) cells. The hMSC treatment in rats showed that TH-ip neuronal loss induced by LPS stimulation in the SN was considerably decreased and was clearly accompanied by a decrease in activation of microglia, as well as TNF-, and iNOS mRNA expression and production of TNF-,. These data suggest that hMSCs have a neuroprotective effect on dopaminergic neurons through anti-inflammatory actions mediated by the modulation of microglial activation. Along with various trophic effects and trans-differentiational potency, the anti-inflammatory properties of MSCs could have major therapeutic implications in the treatment of PD. © 2008 Wiley-Liss, Inc. [source] Chronic inflammation: a failure of resolution?INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 2 2007Toby Lawrence Summary Inflammation has evolved as a protective response to insult or injury, it's a primordial response that eliminates or neutralises foreign organisms or material, the resolution of inflammation encompasses the endogenous anti-inflammatory mechanisms that protect us against excessive tissue injury and promote the restoration of tissue structure and function. In fact, our well being and survival depends upon its efficiency and carefully-balanced control. In general, the innate inflammatory response initiates within minutes and, if all is well, resolves within hours. In contrast, chronic inflammation persists for weeks, months or even years. Here, we are going to discuss the key endogenous checkpoints necessary for mounting an effective yet limited inflammatory response and the crucial biochemical pathways necessary to prevent its persistence. [source] Ketamine attenuates post-operative cognitive dysfunction after cardiac surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009J. A. HUDETZ Background: Post-operative cognitive dysfunction (POCD) commonly occurs after cardiac surgery. Ketamine exerts neuroprotective effects after cerebral ischemia by anti-excitotoxic and anti-inflammatory mechanisms. We hypothesized that ketamine attenuates POCD in patients undergoing cardiac surgery concomitant with an anti-inflammatory effect. Methods: Patients randomly received placebo (0.9% saline; n=26) or an i.v. bolus of ketamine (0.5 mg/kg; n=26) during anesthetic induction. Anesthesia was maintained with isoflurane and fentanyl. A nonsurgical group (n=26) was also included as control. Recent verbal and nonverbal memory and executive functions were assessed before and 1 week after surgery or a 1-week waiting period for the nonsurgical controls. Serum C-reactive protein (CRP) concentrations were determined before surgery and on the first post-operative day. Results: Baseline neurocognitive and depression scores were similar in the placebo, ketamine, and nonsurgical control groups. Cognitive performance after surgery decreased by at least 2 SDs (z -score of 1.96) in 21 patients in the placebo group and only in seven patients in the ketamine group compared with the nonsurgical controls (P<0.001, Fisher's exact test). Cognitive performance was also significantly different between the placebo- and the ketamine-treated groups based on all z -scores (P<0.001, Mann,Whitney U -test). Pre-operative CRP concentrations were similar (P<0.33, Mann,Whitney U -test) in the placebo- and ketamine-treated groups. The post-operative CRP concentration was significantly (P<0.01, Mann,Whitney U -test) lower in the ketamine-treated than in the placebo-treated group. Conclusions: Ketamine attenuates POCD 1 week after cardiac surgery and this effect may be related to the anti-inflammatory action of the drug. [source] Systemic medications: clinical significance in periodonticsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2002Sebastian G. Ciancio Abstract Systemic medications are of value as adjuncts to periodontal therapy. These medications can be divided into two major categories: antibiotics and agents for host modulation. Antibiotics have been shown to be valuable adjuncts in specialized types of periodontal disease, such as localized and generalized aggressive periodontitis, and of possible value in severe chronic periodontitis. Antibiotics have been studied individually, in combination and in sequential therapy. Host modulators include Periostat, non-steroidal anti-inflammatory agents, alendronate (Fosamax), hormone replacement therapy and anti-arthritic medications. These agents produce their beneficial effects by a variety of mechanisms of action, including inhibition of matrix metalloproteinases, inhibition of prostaglandin production, stimulation of osteoblasts, inhibition of osteoclasts, and other anti-inflammatory mechanisms of action. [source] Circulating adiponectin reflects severity of liver disease but not insulin sensitivity in liver cirrhosisJOURNAL OF INTERNAL MEDICINE, Issue 3 2005S. KASER Abstract. Background., The adipocytokine adiponectin has been proposed to play important roles in the regulation of energy homeostasis, insulin sensitivity and shows anti-inflammatory properties. Aim., In this study we investigated the role of circulating adiponectin in different chronic liver diseases, its regulation by systemic anti-tumour necrosis factor (TNF)- , treatment and its hepatic metabolism. Patients and methods., Plasma adiponectin levels were determined in 87 patients with liver cirrhosis of different aetiologies, seven patients with alcoholic steatohepatitis undergoing systemic anti-TNF- , treatment, in 11 patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt implantation and in 21 healthy controls. Results., Adiponectin levels were significantly higher in all subjects with liver cirrhosis of different aetiologies when compared with healthy controls and increased dependent on Child-Pugh classification. In subjects with alcoholic steatohepatitis, systemic anti-TNF- , treatment caused a significant decrease in circulating adiponectin. Adiponectin concentrations were similar in portal, hepatic and peripheral veins. No correlation between adiponectin levels and insulin resistance was found in any patient group. Conclusions., Our data suggest that circulating adiponectin is increased in liver cirrhosis independent of the aetiology of liver disease. We suggest that high adiponectin levels in chronic liver disease might reflect one of the body's anti-inflammatory mechanisms in chronic liver diseases. [source] Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic StudiesALCOHOLISM, Issue 2 2009Michael A. Collins In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions,pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, ,-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways. [source] Review article: anti-inflammatory mechanisms of action of Saccharomyces boulardiiALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2009C. POTHOULAKIS Aliment Pharmacol Ther,30, 826,833 Summary Background,Saccharomyces boulardii, a well-studied probiotic, can be effective in inflammatory gastrointestinal diseases with diverse pathophysiology, such as inflammatory bowel disease (IBD), and bacterially mediated or enterotoxin-mediated diarrhoea and inflammation. Aim, To discuss the mechanisms of action involved in the intestinal anti-inflammatory action of S. boulardii. Methods, Review of the literature related to the anti-inflammatory effects of this probiotic. Results, Several mechanisms of action have been identified directed against the host and pathogenic microorganisms. S. boulardii and S. boulardii secreted-protein(s) inhibit production of proinflammatory cytokines by interfering with the global mediator of inflammation nuclear factor ,B, and modulating the activity of the mitogen-activated protein kinases ERK1/2 and p38. S. boulardii activates expression of peroxisome proliferator-activated receptor-gamma (PPAR-,) that protects from gut inflammation and IBD. S. boulardii also suppresses ,bacteria overgrowth' and host cell adherence, releases a protease that cleaves C. difficile toxin A and its intestinal receptor and stimulates antibody production against toxin A. Recent results indicate that S. boulardii may interfere with IBD pathogenesis by trapping T cells in mesenteric lymph nodes. Conclusions, The multiple anti-inflammatory mechanisms exerted by S. boulardii provide molecular explanations supporting its effectiveness in intestinal inflammatory states. [source] Annexin expression in inflammatory myopathiesMUSCLE AND NERVE, Issue 1 2004Stefan Probst-Cousin MD Abstract The pathogenesis of the inflammatory myopathies is still unclear, making their treatment largely empirical. Improved understanding of the molecular mechanisms of inflammatory muscle injury may, however, lead to the development of more specific immunotherapies. To elucidate a possible pathogenic contribution of calcium-binding proteins such as the annexins, we immunohistochemically investigated muscle biopsy specimens from patients with dermatomyositis (10 cases), polymyositis (9 cases), and inclusion-body myositis (4 cases), compared to control cases comprising sarcoid myopathy (3 cases), Duchenne muscular dystrophy (DMD; 4 cases), and normal muscle (3 cases). We found expression of annexins A1, A2, A4, and A6 in the vascular endothelium of all cases. Myofibers expressed annexins A5, A6, and A7 diffusely and weakly in the cytosol, whereas annexins A5 and A7 were also particularly localized to the sarcolemma. In the inflammatory myopathies, in areas of myonecrosis in DMD, and in granulomatous lesions of sarcoid myopathy, reactivity of annexins A1, A2, A4, A5, and A6 was observed in macrophages and T-lymphocytes. Whereas the latter annexins appear to be nonspecific indicators of activation, annexin A1 upregulation may represent endogenous anti-inflammatory mechanisms that merit further investigation. Muscle Nerve 30: 102,110, 2004 [source] Cranberries (Vaccinium macrocarpon) and Cardiovascular Disease Risk FactorsNUTRITION REVIEWS, Issue 11 2007Diane L. McKay PhD The American cranberry (Vaccinium macrocarpon) is one of the three commercially important fruits native to North America. Cranberries are a particularly rich source of phenolic phytochemicals, including phenolic acids (benzoic, hydroxycinnamic, and ellagic acids) and flavonoids (anthocyanins, flavonols, and flavan-3-ols). A growing body of evidence suggests that polyphenols, including those found in cranberries, may contribute to reducing the risk of cardiovascular disease (CVD) by increasing the resistance ofLDL to oxidation, inhibiting platelet aggregation, reducing blood pressure, and via other anti-thrombotic and anti-inflammatory mechanisms. Research regarding the bioactivity of cranberries and their constituents on risk factors for CVD is reviewed. [source] Association of cytokine gene polymorphisms in CWP and its severity in Turkish coal workersAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 10 2008Ilker Ates PhD Abstract Background Cytokines appear to play a key role in some inflammatory reactions affecting the interactions among pro- and anti-inflammatory mechanisms that result in several diseases such as coal workers' pneumoconiosis (CWP). In this study, to determine the cytokine gene profiles of Turkish coal miners, we performed genotyping analysis to investigate the polymorphisms of CWP-related pro-inflammatory (TNFA, IL1A, IL1B, and IL6) and anti-inflammatory cytokines (IL-1RN and TGFB1). An additional goal was to observe whether these cytokine gene polymorphisms influence the development risk and severity of. Methods Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results TNFA (,238) gene polymorphism principally affected CWP development and severity (OR,=,3.47: 95% CI, 1.12,10.77 and OR,=,4.30: 95% CI, 1.25,14.74, respectively) and also risk of CWP (OR,=,3.79: 95% CI, 1.37,10.46). The TNFA (,308) variant was associated with a risk for the CWP severity (OR,=,2.84: 95% CI, 1.08,7.39). A protective effect of IL6 was found on the development (OR,=,0.48: 95% CI, 0.21,0.93) and severity of CWP (OR,=,0.37: 95% CI, 0.15,0.91). Conclusions We suggest that TNFA (,238) variant may be a risk factor in both development and the severity of CWP, while TNFA (,308) variant seems to be important only in disease severity. On the other hand, IL6 variant may have a protective effect on the development and disease severity. Am. J. Ind. Med. 51:741,747, 2008. Published 2008 Wiley-Liss, Inc. [source] Primate models in women's health: inflammation and atherogenesis in female cynomolgus macaques (Macaca fascicularis)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009Thomas C. Register Abstract Female cynomolgus monkeys are excellent models for understanding cardiovascular disease and the relationships between inflammatory processes and conditions such as atherogenesis. This review summarizes published research findings obtained through comprehensive, multidisciplinary, multi-investigator studies in nonhuman primates over the past two decades. These studies examined the effects of exogenous estrogens and dietary soy protein/isoflavones (IFs) on atherosclerosis, circulating biomarkers, and tissue inflammation in pre- and postmenopausal female cynomolgus monkeys. Inflammation may play a role in the initiation and progression of disease, be a consequence of the disease, or both. Circulating and tissue biomarkers with inflammatory and anti-inflammatory characteristics (including adhesion molecules such as e-selectin, VCAM-1, and ICAM-1, chemokines such as MCP-1, cytokines such as interleukins, and acute phase reactants such as CRP, and others) may be useful indicators of disease status. Treatment of postmenopausal subjects with estrogen resulted in significant reductions in several key inflammatory mediators as well as atherosclerosis, while dietary IF had a more limited effect on inflammation and atherogenesis. Circulating concentrations of key inflammatory proteins, including monocyte-chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6), were associated with atherosclerosis and lesion characteristics in these animals. In premenopausal female monkeys, a diet enriched in soy protein reduced arterial inflammation as well as atherogenesis in comparison to a diet enriched in casein-lactalbumin. Expression levels of arterial inflammation associated genes (MCP-1, ICAM-1) and markers for inflammatory cell types (macrophages and T cells) correlated with plaque size, were differentially influenced by treatments, and represent potential targets for interventions. Arterial expression of estrogen receptor ,, the key mediator of estrogenic effects, was inversely correlated with plaque size and indices of inflammation, suggestive of an atheroprotective role. The findings provide additional evidence that circulating inflammatory markers (particularly MCP-1) may be useful indicators of atherosclerotic disease progression and responses to treatment in female primates, and that estrogens and dietary soy may inhibit atherogenesis in part through anti-inflammatory mechanisms. Am. J. Primatol. 71:766,775, 2009. © 2009 Wiley-Liss, Inc. [source] | |||||||||||||