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Chronic Inflammation (chronic + inflammation)
Selected AbstractsIncreased Sensitivity to the C-X-C Chemokine CINC/gro in a Model of Chronic InflammationMICROCIRCULATION, Issue 2 2000Brent Johnston ABSTRACT Objective: The C-C chemokine MCP-1 elicits significant neutrophil emigration in rats with chronic adjuvant-induced inflammation, but not in naive animals. We examined responses to the C-X-C chemokine CINC/gro to determine whether this class of chemokine elicits altered neutrophil responses during chronic inflammation. Methods: CINC/gro was superfused over mesenteric venules of naive rats or animals with chronic adjuvant-induced vasculitis. Antibodies were used to characterize adhesive mechanisms. Results: CINC/gro elicited leukocyte transendothelial migration in adjuvantimmunized rats at 100-fold lower concentrations than required to elicit transmigration in naive animals. In both groups, neutrophils constituted >95% of the leukocytes recruited by CINC/gro. Using in vitro chemotaxis assays, neutrophils from control and adjuvant-immunized rats responded equally to CINC/gro, suggesting differences in migration were not related to neutrophil phenotype. Differences in adhesion molecule usage were noted in vivo. In control animals, CD18 antibodies blocked CINC/gro-induced neutrophil adhesion and emigration. In adjuvant-immunized animals, an ,4 -integrin antibody reduced adhesion and emigration, while a CD18 antibody selectively inhibited emigration. Conclusions: This study demonstrates increased sensitivity to a C-X-C chemokine in a model of chronic inflammation, implicates the ,4 -integrin in neutrophil adhesion, and demonstrates that CD18 mediates leukocyte transendothelial migration independent from firm adhesion. [source] Iron enhances endothelial cell activation in response to Cytomegalovirus or Chlamydia pneumoniae infectionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2006A. E. R. Kartikasari Abstract Background, Chronic inflammation has been implemented in the pathogenesis of inflammatory diseases like atherosclerosis. Several pathogens like Chlamydia pneumoniae (Cp) and cytomegalovirus (CMV) result in inflammation and thereby are potentially artherogenic. Those infections could trigger endothelial activation, the starting point of the atherogenic inflammatory cascade. Considering the role of iron in a wide range of infection processes, the presence of iron may complicate infection-mediated endothelial activation. Materials and methods, Endothelial intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) expression were measured using flow cytometry, as an indication of endothelial activation. Cytotoxicity was monitored using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Immunostaining was applied to measure Cp and CMV infectivity to endothelial cells. Results, An increased number of infected endothelial cells in a monolayer population leads to a raised expression of adhesion molecules of the whole cell population, suggesting paracrine interactions. Iron additively up-regulated Cp-induced VCAM-1 expression, whereas synergistically potentiated Cp-induced ICAM-1 expression. Together with CMV, iron also enhanced ICAM-1 and VCAM-1 expression. These iron effects were observed without modulation of the initial infectivity of both microorganisms. Moreover, the effects of iron could be reversed by intracellular iron chelation or radical scavenging, conforming modulating effects of iron on endothelial activation after infections. Conclusions, Endothelial response towards chronic infections depends on intracellular iron levels. Iron status in populations positive for Cp or CMV infections should be considered as a potential determinant for the development of atherosclerosis. [source] The Effect of Helicobacter pylori Infection on Levels of DNA Damage in Gastric Epithelial CellsHELICOBACTER, Issue 5 2002S. M. Everett Abstract Background.Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells. Methods. Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage. Results. DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5,75.8), n = 18 and 21% (11.9,29.8), n = 65, respectively, p < .001]. Intermediate levels were found in reactive gastritis [55.5% (41.3,71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3,60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3,51.0), p = .007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = ,.92 and ,.88 for normal mucosa and H. pylori gastritis, respectively). Conclusions. Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis. [source] Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancerINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Melissa A. Merritt Abstract Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia-wide case,control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population-based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01,1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03,1.44 and 1.18, 95% CI 0.81,1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti-inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. © 2007 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] Increased soluble CD40 ligand levels in cystic fibrosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2004A. Falco Summary., Chronic inflammation represents a key pathogeneric event in the progression of lung disease in cystic fibrosis (CF). To identify novel mechanisms of the inflammatory reaction in CF and analyze its relation with coagulative activation, we carried-out a cross-sectional study to evaluate circulating levels of the inflammatory mediators soluble (s) CD40L, C-reactive protein (CRP), interleukin (IL)-1,, the coagulation markers activated factor VII (FVIIa) and prothrombin fragment (F) 1+2, as well as urinary 11-dehydro-thromboxane (TX)B2, an index of in vivo platelet activation, in 34 CF patients and 34 matched healthy subjects. We observed that CF patients displayed significantly increased circulating levels of sCD40L compared to controls [2.8 (0.4,15.6) vs 1.1 (0.2,2.7) ng mL,1 ,P = 0.0003]. sCD40L levels inversely correlated with forced expiratory volume at 1 second (FEV1) (, = ,0.788, P = 0.0001), whereas it directly correlated with CRP and IL-1, levels (, = 0.621, P = 0.0004; and , = 0.745, P = 0.0001, respectively), which were also elevated in CF patients. CF patients had also enhanced levels of FVIIa and F1+2 compared to controls [39.2 (22.6,69.8) vs 22.3 (16.2,32.4) mU mL,1, P = 0.0001; 0.60 (0.30,1.80) vs 0.17 (0.10,0.40) nmol L,1, P = 0.0001, respectively]. A direct correlation was observed between sCD40L and both plasma FVIIa (, = 0.691, P = 0.0001) and F1+2 (, = 0.545, P = 0.0017) as well as between sCD40L and urinary 11-dehydro-TXB2 (, = 0.433, P = 0.0129). Our findings suggest that in CF patients, sCD40L could represent a biochemical link between the inflammatory state, and endothelial damage and coagulative activation, leading to progressive impairment of pulmonary function. [source] Chronic inflammation in asthma: a contest of persistence vs resolutionALLERGY, Issue 9 2008C. L. Van Hove Recent investigations have highlighted that endogenous anti-inflammatory mediators and immune regulating mechanisms are important for the resolution of inflammatory processes. A disruption of these mechanisms can be causally related not only to the initiation of unnecessary inflammation, but also to the persistence of several chronic inflammatory diseases. In asthma, chronic Th-2 driven eosinophilic inflammation of the airways is one of the central abnormalities. To date, elucidating the role of the different pro-inflammatory mediators involved in orchestrating the inflammatory processes in asthma has been the subject of intense research in both humans and animal models. However, the counter-regulatory mechanisms that co-determine the outcome in the contest of resolution vs persistence of the eosinophilic airway inflammation remain poorly understood. These are currently being investigated in animal models of chronic asthma. Elucidating these mechanisms is of relevance, since it can give rise to a new therapeutic approach in the treatment of chronic airway inflammation in asthmatics. This novel concept of treatment involves the stimulation of endogenous anti-inflammatory pathways, rather than solely antagonising the various pro-inflammatory mediators. Here, we review and discuss the current knowledge about these endogenous anti-inflammatory mediators in clinical and experimental asthma. [source] Chronic inflammation, periodontitis and cardiovascular diseasesORAL DISEASES, Issue 2 2008AD Hingorani [source] Chronic inflammation in dialysis patients , periodontal disease, the new kid on the blockORAL DISEASES, Issue 1 2008P Kotanko [source] Monocyte chemotactic protein-1 (MCP-1/CCL2) is associated with prostatic growth dysregulation and benign prostatic hyperplasiaTHE PROSTATE, Issue 5 2010Kazutoshi Fujita Abstract BACKGROUND Chronic inflammation is commonly observed in benign prostate hyperplasia (BPH), and prostate tissue often contains increased inflammatory infiltrates, including T cells and macrophages. Cytokines are not only key mediators of inflammation but may also play important roles in the initiation and progression of BPH. METHODS In order to determine what cytokines might be involved in prostatic enlargement, expressed prostatic secretions (EPS) from ex vivo prostates were analyzed by human cytokine antibody microarray and ELISA. Prostate epithelial cells (PrEC) and prostate stromal cells (PrSC) were used for ELISA, proliferation, and Western blot assays. RESULTS Monocyte chemotactic protein-1 (MCP-1/CCL2) was one of the most elevated proteins in secretions from large prostate glands. PrSC were found to secrete MCP-1; Western blotting showed that both PrSC and PrEC express the MCP-1 receptor CCR2 which by RT-PCR was the CCR2b isoform. Proliferation assays showed that MCP-1 stimulates the proliferation of PrEC, but not PrSC, and that a specific MCP-1 antagonist (RS102895) suppressed this effect. Conditioned medium from PrSC stimulated the proliferation of PrEC as well, an effect completely inhibited by both RS102895 and a neutralizing anti-MCP-1 monoclonal antibody. The inflammatory cytokines interleukin (IL)-1,, interferon-,, and IL-2 enhanced the secretion of MCP-1 from PrEC and PrSC. In addition, MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 in the same secretions. CONCLUSIONS The cytokine MCP-1, of apparent prostatic stromal cell origin, may play an important role in prostatic enlargement and BPH, and is a candidate biomarker for these pathologic processes. Prostate 70: 473,481, 2010. © 2009 Wiley-Liss, Inc. [source] Proinflammatory Cytokines, Hepatocyte Growth Factor and Adipokines in Peritoneal Dialysis PatientsARTIFICIAL ORGANS, Issue 7 2010Chien-Te Lee Abstract Chronic inflammation is a well-recognized complication in dialysis patients and a potential role of the adipose tissue as an important tissue of origin contributing to inflammation has been proposed. Stable peritoneal dialysis (PD) patients were enrolled to investigate the relationship between serum levels of proinflammatory cytokines and adipokines. Our results revealed that there was a strong association between high sensitivity C-reactive protein and interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-,) but not with IL-10 and IL-18. IL-6 correlated with TNF-,, IL-10, and IL-18. No association was found between IL-10 and IL-18. Adiponectin was positively correlated with all proinflammatory cytokines, except IL-10. No significant association was found between resistin and proinflammatory cytokines. Hepatocyte growth factor (HGF) was directly related to proinflammatory cytokines but not with adipokines. The presence of residual kidney function (RKF) affected IL-6, TNF-,, and HGF levels. The peritoneal transport property did not influence inflammatory cytokine and adipokine levels. In conclusion, there was a close relationship between proinflammatory cytokines and adipokines. HGF correlated with proinflammatory cytokines but not with adipokines. The PD-related factors such as RKF, peritoneal property and dialysis glucose load affected levels of proinflammatory cytokines. Body mass index was an important determinant of leptin and adiponectin in PD patients. [source] 2132: Celastrol regulates innate immunity response via NF-kB and HSP70 in ARPE-19 cellsACTA OPHTHALMOLOGICA, Issue 2010T PAIMELA Purpose Chronic inflammation participates in the pathology of age-related macular degeneration (AMD). Recent studies indicate that celastrol, a novel triterpene compound, modulates inflammatory responses, but its effect on the human retinal pigment epithelial cells is poorly understood. In this study, we investigated the potential anti-inflammatory role of celastrol and its effect on nuclear factor kappa B (NF-kB) activity in human retinal pigment epithelial cells (ARPE-19). Methods ARPE-19 cells were exposed to lipopolysaccharide (LPS; TLR 4 agonist) with simultaneous exposure to various concentrations of celastrol and the secretion of IL-6 cytokine was analyzed by ELISA. The effect of celastrol exposure on heat shock protein 70 (HSP70) expression was analyzed by western blotting. In response to celastrol and modulated HSP70 levels NF-kB activity was examined by ELISA. Results Celastrol suppressed the LPS-induced IL-6 expression levels via NF-kB transcription factor in ARPE-19 cells. Celastrol evoked elevated HSP70 levels without cytotoxicity. Interestingly, celastrols capability to inhibit NF-kB activity was diminished when HSP70 response was suppressed by siRNA. This reveals that celastrol has potent anti-inflammatory capacity in ARPE-19 cells, and its effect is modulated through NF-kB and HSP70. Conclusion Our findings reveal that celastrol is a novel compound to suppress innate immunity response in human retinal pigment epithelial cells. [source] The long-term impact of ferritin level on treatment and complications of type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 6 2008L. Jiang Aim:, To investigate if high-serum ferritin has long-term impact on response to treatment and the development of diabetic complications in patients with type 2 diabetes. Research design and methods:, We analysed the record of 90 consecutive type 2 diabetic subjects who had serum ferritin level determined soon after diagnosis of diabetes and who also had long-term follow-up data. Results:, Patients with higher serum ferritin level had slightly worse triglyceride, blood pressure and liver enzyme levels at the end of follow up. However, ferritin level had no impact on the initial or final requirements for diabetic medication and the development of diabetic complications. Conclusions:, Although elevated serum ferritin is a marker of insulin resistance and chronic inflammation, it is not necessarily a bad prognostic indicator that should affect the clinician's approach to management. [source] Inflamed adipose tissue, insulin resistance and vascular injuryDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2008Christian X. Andersson Abstract Type 2 diabetes is the most common metabolic disorder today and has reached epidemic proportions in many countries. Insulin resistance and inflammation play a central role in the pathogenesis of type 2 diabetes and are present long before the onset of the disease. During this time, many of the complications associated with type 2 diabetes are initiated. Of major concern is the two- to fourfold increase in cardiovascular morbidity and mortality in this group compared to a nondiabetic population. Obesity, characterized by enlarged fat cells, and insulin resistance are, like type 2 diabetes, associated with impaired adipogenesis and a low-grade chronic inflammation that to a large extent emanates from the adipose tissue. Both these processes contribute to unfavourable alterations of the circulating levels of several bioactive molecules (adipokines) that are secreted from the adipose tissue, many of which have documented inhibitory effects on insulin sensitivity in the liver and peripheral tissues and, in addition, have negative effects on the cardiovascular system. Here we review current knowledge of the adipose tissue as an endocrine organ, the local and systemic effects of a chronic state of low-grade inflammation residing in the adipose tissue, and, in particular, the effects of inflammation and circulating adipokines on the vascular wall. Copyright © 2008 John Wiley & Sons, Ltd. [source] Inflammation and the etiology of type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 1 2006Åke Sjöholm Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-,. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis. Copyright © 2005 John Wiley & Sons, Ltd. [source] Utility of fine-needle aspiration cytology in the classification of leprosyDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2001I. Satish Rao M.D. Abstract The role of fine-needle aspiration cytology (FNAC) in the diagnosis of benign skin lesions has been restricted primarily to the evaluation of bacteriologic and morphologic indices in leprosy. This study was undertaken to evaluate the efficacy of FNAC in the diagnosis and classification of lepromatous lesions. Aspirates of 94 newly diagnosed cases of leprosy were studied, and the bacterial load was determined by modified Ziehl-Neelsen (ZN) stain. A skin biopsy was taken from the same site at the same sitting. Frozen and paraffin sections stained with hematoxylin-eosin (H&E) and ZN stains were examined from the biopsy specimen. In 61 of 94 cases (64.9%), the aspirates were satisfactory. Both diagnosis and classification of leprosy were possible in 40 of these 61 cases; the rest of the aspirates showed nonspecific chronic inflammation. The 39 cases of leprosy where a biopsy was available from the same site were classified on FNAC into tuberculoid (TT and BT), lepromatous (LL and BL), and midborderline (BB) subtypes. Taking the histologic diagnosis and Ridley-Jopling classification to be the gold standard, a strong concordance in tuberculoid leprosy cases (18 of 20 cases, 90%) and in lepromatous cases (15 of 16 cases, 93.7%) was observed. Midborderline cases of leprosy posed a problem, and a correct cytohistological correlation was observed in only one of the three cases. Diagn. Cytopathol. 24:317,321, 2001. © 2001 Wiley-Liss, Inc. [source] HIF-1, protein expression is associated with the environmental inflammatory reaction in Barrett's metaplasiaDISEASES OF THE ESOPHAGUS, Issue 8 2009F. C. Ling SUMMARY The oxygen-regulated transcription factor subunit hypoxia inducible factor-1, (HIF-1,) is involved in angiogenesis, energy metabolism, cell survival, and inflammation. We examined the protein expression of HIF-1, within the progression of Barrett's sequence as well as the type and degree of the environmental inflammatory reaction. Squamous epithelium (SE), metaplastic, low- and high-grade dysplastic lesions, and tumor tissue of 57 resection specimens from patients with Barrett's adenocarcinoma were immunohistochemically analyzed. Active and chronic inflammatory reactions were classified according to the Updated Sydney System. HIF-1, protein expression increased significantly from SE to Barrett's metaplasia (BM) (P < 0.0001). From metaplasia through low- and high-grade dysplasia to cancer, no further increase could be detected. Active and chronic inflammation were also significantly different between SE and BM (P < 0.0001) but not during further progression in the sequence. HIF-1, protein expression did not correlate with histopathologic parameters or survival. HIF-1, protein expression pattern resembles the active and chronic environmental inflammatory reaction. All were significantly increased in metaplasia compared to SE without further change in tumor development. HIF-1, protein expression appears to be associated with inflammatory processes in the development of BM. [source] Evaluation of systemic oxidative status and mononuclear leukocytes DNA damage in children with caustic esophageal strictureDISEASES OF THE ESOPHAGUS, Issue 4 2006M. Kaya SUMMARY., Esophageal stricture (ES) due to accidentally caustic digestions is a common problem in children. Mucosal damage and repeated dilatations lead to chronic inflammation and finally ES. We investigated the oxidative status and DNA damage of children with ES. Five children with ES were compared with the same age- and sex-matched healthy subjects. Oxidative status of plasma was evaluated by measuring myeloperoxidase (MPO) activity, and total peroxide (TP) level. Anti-oxidative status of the plasma was evaluated by measuring catalase (CAT) activity, and total antioxidant response (TAR). We used the Single Cell Gel Electrophoresis (also called Comet Assay) to measure DNA strand break in peripheral blood mononuclear leukocytes. Mean MPO activity and TP levels in the ES group were significantly higher than the control group (0.83 ± 0.35, 0.09 ± 0.03 and 0.98 ± 0.38, 0.34 ± 0.20, P = 0.009 and P = 0.047 respectively). There was no significant difference in CAT activity and TAR levels between the two groups (P = 0.347). DNA damage in patients with ES was increased compared to control subjects (108.8 ± 51.2 and 57.6 ± 31.2 arbitrary units, respectively), but this difference was not significant statistically (P= 0.09). This study shows that systemic oxidative stress and alteration at the nuclear level occur in patients with ES, as a result of multiple dilatations and tissue injury. On the other hand, these results support that patients with ES may benefit from antioxidant treatment. [source] Salient virulence factors in anaerobic bacteria, with emphasis on their importance in endodontic infectionsENDODONTIC TOPICS, Issue 1 2004Ingar Olsen Endodontic infections by microbial invasion of the necrotic pulp lead to apical periodontitis of both acute and chronic forms. Acute lesions often develop from multiplication of bacteria in primary infections. Such lesions may also occur as exacerbations of chronic forms provoked for example in conjunction with endodontic treatment measures. The clinical course appears related to the character of the microflora. While primary infections are predominated by a mixed flora of anaerobic bacteria and resembles that of aggressive marginal periodontitis, chronic forms of apical periodontitis emerge following regression of the acute infection, whereupon prevailing bacteria have assumed low activity. The significance of virulence factors is easy to understand as far as acute inflammatory conditions are concerned. The role of virulence factors for sustaining chronic inflammation is more unclear and complex. This review is about salient virulence factors in some selected bacterial genera such as Peptostreptococcus, Porphyromonas, Prevotella and Fusobacterium, which often predominate the root canal microbiota in the acute phase of endodontic infections. [source] Relationships between cagA, vacA, and iceA genotypes of Helicobacter pylori and DNA damage in the gastric mucosaENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004Marcelo S.P. Ladeira Abstract Helicobacter pylori (H. pylori) is believed to predispose carriers to gastric cancer by inducing chronic inflammation. The inflammatory processes may result in the generation of reactive oxygen and nitrogen species that damage DNA. In this study, we investigated the relationships between DNA damage in the gastric mucosa and cagA, vacA, and iceA genotypes of H. pylori. The study was conducted with biopsies from the gastric antrum and corpus of 98 H. pylori -infected and 26 uninfected control patients. H. pylori genotypes were determined by PCR and DNA damage was measured in gastric mucosal cells by the Comet assay (single cell gel electrophoresis). All patients were nonsmokers, not abusing alcohol, and not using prescription or recreational drugs. Levels of DNA damage were significantly higher (P < 0.0001) in the H. pylori -infected patients than in uninfected patients. In comparison with the level of DNA damage in the uninfected controls, the extent of DNA damage in both the antrum (OR = 8.45; 95% CI = 2.33,37.72) and the corpus (OR = 6.55; 95% CI = 2.52,17.72) was related to infection by cagA+/vacAs1m1 and iceA1 strains. The results indicate that the genotype of H. pylori is related to the amount of DNA damage in the gastric mucosa. These genotypes could serve as biomarkers for the risk of extensive DNA damage and possibly gastric cancer. Environ. Mol. Mutagen. 44:91,98, 2004. © 2004 Wiley-Liss, Inc. [source] Nitric oxide and p53 in cancer-prone chronic inflammation and oxyradical overload disease,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2004Julie E. Goodman Abstract Nitric oxide (NO·), which is generated under chronic inflammatory conditions that predispose individuals to cancer, has paradoxical effects. NO· can activate p53, which can result in anti-carcinogenic effects, or it can be mutagenic and increase cancer risk. We explored the mechanisms by which NO· induced p53 activation in vitro and found that NO· induced p53 accumulation and phosphorylation, particularly at ser-15, via ATM and ATR kinases, which then led to cell cycle arrest at G2/M. We next examined proteins in these pathways in both inflamed and normal human colon tissue. Inducible nitric oxide synthase (iNOS) levels and p53-P-ser15 levels were positively correlated with the degree of inflammation and with each other. Additionally, the p53 targets, HDM-2 and p21 (WAF1), were present in ulcerative colitis (UC) colon, but undetectable in normal colon, consistent with activated p53. We also found higher p53 mutant frequencies of both G:C , A:T transitions at the CpG site of codon 248 and C:G , T:A transitions at codon 247 in lesional colon tissue from UC cases versus nonlesional tissue from these cases or colon tissue from normal adult controls. Consistent with nitrosative stress and the deamination of 5-methylcytosine, p53 mutations were also detected in sporadic colon cancer tissue and were associated with iNOS activity in these tissues. These studies identified a potential mechanistic link between NO· and p53 in UC and sporadic colon cancer. Environ. Mol. Mutagen. 44:3,9, 2004. Published 2004 Wiley-Liss, Inc. [source] End-stage renal disease: a state of chronic inflammation and hyperleptinemiaEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003R. Pecoits-Filho No abstract is available for this article. [source] Acquisition of regulatory function by human CD8+ T cells treated with anti-CD3 antibody requires TNFEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2010Vitaly Ablamunits Abstract Anti-CD3 mAb can modulate graft rejection and attenuate autoimmune diseases but their mechanism(s) of action remain unclear. CD8+ T cells with regulatory function are induced in vitro by Teplizumab, a humanized anti-CD3 antibody and inhibit responses of autologous and allogeneic T cells. They inhibit CD4+ T-cell proliferation by mechanisms involving TNF and CCL4, and by blocking target cell entry into G2/M phase of cell cycle but neither kill them, nor compete for IL-2. CD8+ Treg can be isolated from peripheral blood following treatment of patients with Type 1 diabetes with Teplizumab, but not from untreated patients. The induction of CD8+ Treg by anti-CD3 mAb requires TNF and signaling through the NF-,B cascade. The CD8+ Treg express CD25, glucocorticoid-induced TNF receptor family, CTLA-4, Foxp3, and TNFR2, and the combined expression of TNFR2 and CD25 identifies a potent subpopulation of CD8+ Treg. These studies have identified a novel mechanism of immune regulation by anti-CD3 mAb and markers that may be used to track inducible CD8+ Treg in settings such as chronic inflammation or immune therapy. [source] IL-22 and inflammation: Leukin' through a glass onionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2008Lauren A. Zenewicz Abstract IL-22 is a Th17,T-cell-associated cytokine that is highly expressed during chronic inflammation. IL-22 receptor expression is absent on immune cells, but is instead restricted to the tissues, providing signaling directionality from the immune system to the tissues. Through Stat3 signaling, IL-22 induces a variety of proliferative, anti-apoptotic, and anti-microbial pathways. IL-22 is bi-functional with both pro-inflammatory and protective effects on tissues depending on the inflammatory context. The cytokine plays a role both in the host response against extracellular pathogens and in the inflammation associated with autoimmune diseases. Therapeutics targeting IL-22 therefore may have promise for treating various chronic inflammatory diseases. [source] A pseudosymmetric cell adhesion regulatory domain in the ,7 tail of the integrin ,4,7 that interacts with focal adhesion kinase and srcEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2006Geoffrey Abstract The ,7 integrins ,4,7 and ,E,7 play key roles in forming the gut-associated lymphoid tissue, and contribute to chronic inflammation. The ,4,7 integrin-mediated adhesion of activated lymphocytes is largely due to a transient increase in avidity from ligand-induced clustering of ,4,7 at the cell-surface. Here, we report that L and D enantiomers of a cell-permeable peptide YDRREY encompassing residues 735,740 of the cytoplasmic tail of the ,7 subunit inhibit the adhesion of T cells to ,7 integrin ligands. The YDRREY peptide abrogated mucosal addressin cell adhesion molecule-1-induced clustering of ,4,7 on the surface of activated T cells. A mutated form of the YDRREY peptide carrying either single or double conservative mutations at Tyr735Phe and Tyr740Phe was unable to inhibit T cell adhesion, suggesting that both tandem tyrosines are critical for activity. The YDRREY peptide was bound and phosphorylated by focal adhesion kinase and src, which may serve to sequester cytoskeletal proteins to the cytoplasmic domain of ,4,7. The quasi-palindromic sequence YDRREY within the ,7 cytoplasmic tail constitutes a cell adhesion regulatory domain that modulates the interaction of ,7-expressing leukocytes with their endothelial and epithelial ligands. Cell-permeable peptidomimetics based on this motif have utility as anti-inflammatory reagents for the treatment of chronic inflammatory disease. [source] Inflammation alters somatostatin mRNA expression in sensory neurons in the ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005Seham A. Abd El-Aleem Abstract Proinflammatory neuropeptides, such as substance P and calcitonin gene-related peptide, are up-regulated in primary afferent neurons in acute and chronic inflammation. While these neuropeptides have been intensively studied, potentially anti-inflammatory and/or anti-nociceptive neuropeptides such as somatostatin (SS) have been less widely investigated. Endogenous somatostatin is thought to exert a tonic antinociceptive effect. Exogenous SS is anti-inflammatory and antinociceptive and is thought to exert these actions through inhibition of proinflammatory neuropeptide release. In this study we have compared the expression of somatostatin in two inflammatory models: arthritis, a condition associated with increased nociception, and periodontitis, in which there is little evidence of altered nociceptive thresholds. In acute arthritis (< 24 h) SS mRNA was down-regulated in ipsilateral dorsal root ganglia (DRG; 52 ± 7% of control, P < 0.05), and up-regulated in contralateral DRG (134 ± 10% of control; P < 0.05). In chronic arthritis (14 days) this pattern of mRNA regulation was reversed, with SS being up-regulated ipsilaterally and down-regulated contralaterally. In chronic mandibular periodontitis (7,10 days), SS mRNA was up-regulated in only the mandibular division of the ipsilateral trigeminal ganglion (TG) (day 7, 219 ± 9% and day 10, 217 ± 12% of control; P < 0.02) but showed no change in other divisions of the trigeminal ganglion or in the mesencephalic nucleus. These data show that antinociceptive and anti-inflammatory neuropeptides are also regulated in inflammation. It is possible that the degree of inflammation and nociception seen may depend on the balance of pro- and anti-inflammatory and nociceptive peptide expression in a particular condition. [source] Photoaging and oxidative stressEXPERIMENTAL DERMATOLOGY, Issue 2003Chikako Nishigori Abstract Photoaging is significantly different from chronological aging in both clinical and histological appearance. It has been suggested that oxidative stress, generated by ultraviolet radiation (UVR), leads to photoaging over a long period. The presence of 8-OHdG, and oxidatively modified proteins such as 4-hydroxy-2-nonenal-modified protein, 3- l -nitro-tyrosine and N,,(carboxymethyl)lysine in UV-exposed skin specimens, supports this theory. The pathophysiology of photoaging of the skin caused by chronic inflammation after UVR is reviewed and discussed, with a focus on oxidative stress. [source] Seropositivity to Helicobacter pylori heat shock protein 60 is strongly associated with intensity of chronic inflammation, particularly in antrum mucosa: an extension of an 18-year follow-up study of chronic gastritis in Saaremaa, EstoniaFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2001Tamara Vorobjova Abstract Helicobacter pylori is a cause of chronic gastritis and leads to development of atrophy in some cases. There is evidence that the heat shock protein 60 (HSP60) of H. pylori is involved in induction of chronic inflammation. Seroprevalence of IgG antibodies to H. pylori HSP60 in an adult cohort from Saaremaa, Estonia (68 persons, median age 57 years), with a high prevalence of antibodies to cell surface proteins of H. pylori (92%) and a well characterized dynamics of chronic gastritis in an 18-year follow-up study, was tested using purified H. pylori HSP60 at a concentration of 1 ,g ml,1 with ELISA. The state of the gastric mucosa and the presence of H. pylori in histological sections in the samples of 1979 and 1997 were assessed in accordance with the Sydney system. Seropositivity for H. pylori HSP60 was 65%. Immunological response to H. pylori HSP60 is associated with the morphological presence of H. pylori in the antrum and corpus (P=0.01) and is strongly correlated with the grade of chronic inflammation, particularly in the antrum mucosa (r=0.34; P=0.003; OR=5.97 (95% CI 1.21,29.3)), but is not associated with development of atrophy during 18 years of follow-up, or with the activity of gastritis. This finding supports the evidence that immunological response to H. pylori HSP60 may play a role in triggering of the inflammatory process in the gastric mucosa. [source] Prostaglandin E synthase in the pathophysiology of arthritisFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2005Fumiaki Kojima Abstract Prostaglandin E synthase (PGES) is a recently identified terminal enzyme that acts downstream of cyclooxygenase and catalyzes the conversion of prostaglandin (PG) H2 to PGE2. At least three isozymes have been cloned so far, which are called membrane-associated PGES (mPGES)-1, mPGES-2, and cytosolic PGES. Among them, mPGES-1 is induced by various inflammatory stimuli in some cells and tissues. Induction of mPGES-1 in the component of articular tissues of patients with rheumatoid arthritis and osteoarthritis has been demonstrated in vitro. Recent studies using adjuvant induced arthritis model have shown the increase of mPGES-1 expression resulted in the increase of PGE2 production at the sites of inflammation. In addition, reports of mPGES-1-deficient mice clearly suggest the role of mPGES-1 in the process of chronic inflammation such as collagen-induced arthritis and collagen antibody induced arthritis in vivo. Thus, recent in vitro and in vivo findings suggest that mPGES-1 may be a novel therapeutic target for arthritis. This paper introduces recent advances in research about the role of PGES in the pathophysiology of arthritis. [source] The dual function of hepatic SOCS3 in insulin resistance in vivoGENES TO CELLS, Issue 2 2007Takehiro Torisu Inflammation associates with insulin resistance, which dysregulates nutrient homeostasis and leads to diabetes. The suppressor of cytokine signaling 3 (SOCS3), which is induced by pro-inflammatory cytokines, such as TNF, and IL-6, has been implicated in inflammation-mediated insulin resistance in the liver and adipocytes. However, no genetic evidence has been provided for the involvement of SOCS3 on insulin resistance. Here, we generated hepatocyte-specific SOCS3-deficient (L-SOCS3 cKO) mice and examined insulin sensitivity. Being consistent with a previous idea, the loss of SOCS3 in the liver apparently improved insulin sensitivity. However, unexpectedly, L-SOCS3 cKO mice exhibited obesity and systemic insulin resistance with age. Insulin signaling was rather suppressed in muscles, suggesting that deletion of the SOCS3 gene in the liver modulates insulin sensitivity in other organs. Anti-inflammatory reagent, sodium salicylate, partial improved insulin resistance of aged L-SOCS3 cKO mice, suggesting that enhanced inflammatory status is associated with the phenotype of these mice. STAT3 was hyperactivated and acute-phase proteins were elevated in L-SOCS3 cKO mice liver, which were reduced by sodium salicylate treatment. We conclude that hepatic SOCS3 is a mediator of insulin resistance in the liver; however, lack of SOCS3 in the liver promotes systemic insulin resistance by mimicking chronic inflammation. [source] | |||||||||||||||||||||||||||||||||||||||||||