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Receptor II (receptor + ii)
Selected AbstractsAstrocyte and endothelial cell expression of ADAM 17 (TACE) in adult human CNSGLIA, Issue 4 2001Diane R. Goddard Abstract ADAM 17, also known as TACE, is an important sheddase for a number of proteins, including tumor necrosis factor-, (TNF-,), transforming growth factor-, (TGF-,), L-selectin, p75, and p55 TNF receptors, and interleukin-1 receptor II (IL-1RII). The presence of ADAM 17 mRNA in adult mouse and rat CNS was recently reported (Karkkainen et al. Mol Cell Neurosci 15:547,560, 2000). However, the cellular origin of ADAM 17 remains unknown. In this study, we have used an anti-ADAM 17 antibody in an immunohistochemical study of its distribution in human adult CNS tissue. Cells with astrocytic and endothelial morphology were ADAM 17-positive. This finding was further confirmed using double immunofluorescence with antibodies against GFAP and von Willebrand factor, which label astrocytes and endothelial cells, respectively. This study demonstrates that ADAM 17 is expressed by astrocytes and endothelial cells in normal brain tissue and may have a role in normal brain function. GLIA 34:267,271, 2001. © 2001 Wiley-Liss, Inc. [source] Deletion of interleukin-6 in mice with the dominant negative form of transforming growth factor , receptor II improves colitis but exacerbates autoimmune cholangitis,HEPATOLOGY, Issue 1 2010Weici Zhang The role of interleukin-6 (IL-6) in autoimmunity attracts attention because of the clinical usage of monoclonal antibodies to IL-6 receptor (IL-6R), designed to block IL-6 pathways. In autoimmune liver disease, activation of the hepatocyte IL-6/STAT3 (signal transducer and activator of transcription 3) pathway is associated with modulating pathology in acute liver failure, in liver regeneration, and in the murine model of concanavalin A,induced liver inflammation. We have reported that mice expressing a dominant negative form of transforming growth factor , receptor II (dnTGF,RII) under control of the CD4 promoter develop both colitis and autoimmune cholangitis with elevated serum levels of IL-6. Based on this observation, we generated IL-6,deficient mice on a dnTGF-,RII background (dnTGF,RII IL-6,/,) and examined for the presence of antimitochondrial antibodies, levels of cytokines, histopathology, and immunohistochemistry of liver and colon tissues. As expected, based on reports of the use of anti,IL-6R in inflammatory bowel disease, dnTGF,RII IL-6,/, mice manifest a dramatic improvement in their inflammatory bowel disease, including reduced diarrhea and significant reduction in intestinal lymphocytic infiltrates. Importantly, however, autoimmune cholangitis in dnTGF,RII IL-6,/, mice was significantly exacerbated, including elevated inflammatory cytokines, increased numbers of activated T cells, and worsening hepatic pathology. Conclusion: The data from these observations emphasize that there are distinct mechanisms involved in inducing pathology in inflammatory bowel disease compared to autoimmune cholangitis. These data also suggest that patients with inflammatory bowel disease may not be the best candidates for treatment with anti,IL-6R if they have accompanying autoimmune liver disease and emphasize caution for therapeutic use of anti,IL-6R antibody. HEPATOLOGY 2010 [source] Transforming growth factor- , stimulates Interleukin-11 production by human periodontal ligament and gingival fibroblastsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2006R. Yashiro Abstract Background: Transforming growth factor (TGF)- , is a potent multifunctional polypeptide, abundant in the bone matrix. Interleukin (IL)-11 is a pleiotropic cytokine with effects on multiple cell types. The present study was performed to evaluate the regulatory effects of TGF- , on IL-11 production by human periodontal ligament cells (PDL) and human gingival fibroblasts (HGF). Material and Methods: The expression of TGF- , receptor in PDL and HGF were observed using flow cytometry. PDL and HGF were stimulated with TGF- , with or without protein kinase C (PKC) inhibitors and activator. IL-11, bone morphogenetic protein-2 (BMP-2) and TGF- , mRNA expression was quantified by real-time polymerase chain reaction (PCR). IL-11 production was measured using enzyme-linked immunosorbent assay. Results: PDL and HGF expressed both TGF- , receptor I and TGF- , receptor II on the cell surfaces. IL-11 mRNA expression and IL-11 production were augmented by TGF- , in both PDL and HGF, with higher values in PDL. PKC inhibitors partially suppressed TGF- , -induced IL-11 production in PDL and HGF, whereas activator enhanced it. TGF- , mRNA and BMP-2 mRNA expression were up-regulated by TGF- , in PDL. Conclusion: These results suggest that PDL produce IL-11 in response to TGF- ,. [source] Expression of adiponectin and its receptors in livers of morbidly obese patients with non-alcoholic fatty liver diseaseJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 2 2009Hong Ma Abstract Background and Aim:, Obesity is one of the risk factors for non-alcoholic fatty liver disease (NAFLD) and a common disease that comprises simple steatosis and non-alcoholic steatohepatitis (NASH), and can eventually lead to liver cirrhosis. Adiponectin is an adipocyte-derived protein that has anti-obesity, antidiabetic and anti-inflammatory properties, and is considered to possess a hepatoprotective function. Its role in the development and progression of NAFLD in morbidly obese patients is unknown. In this study, we examined the expression levels of adiponectin and its receptors in liver biopsies of morbidly obese patients and then determined whether there was an association with the disease severity. Methods:, Liver biopsies from 30 morbidly obese patients (18 NASH vs 12 steatosis) were analyzed. The needle core biopsies were subjected to routine histological examination and stained immunohistochemically for adiponectin, adiponectin receptor I (adipoRI) and receptor II (adipoRII). Results:, The two groups were comparable with respect to body mass index, age and gender distribution. The expression of adiponectin decreased in liver biopsies with NASH as compared to those with simple steatosis (1.61 ± 0.70 vs 2.25 ± 0.75, P = 0.028). Spearman's rank correlation coefficient analysis showed that the staining intensity of adiponectin negatively correlated with the grade of inflammation (r = ,0.368, P = 0.045) and stage of fibrosis (r = ,0.380, P = 0.038). There was no significant difference in expression of adipoRI and adipoRII between the two groups. Conclusion:, These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients. [source] Human single-chain variable fragment that specifically targets arthritic cartilageARTHRITIS & RHEUMATISM, Issue 4 2010Chris Hughes Objective To demonstrate that posttranslational modification of type II collagen (CII) by reactive oxygen species (ROS), which are known to be present in inflamed arthritic joints, can give rise to epitopes specific to damaged cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA) and to establish a proof of concept that antibodies specific to ROS-modified CII can be used to target therapeutics specifically to inflamed arthritic joints. Methods We used a semisynthetic phage display human antibody library to raise single-chain variable fragments (scFv) specific to ROS-modified CII. The specificity of anti,ROS-modified CII scFv to damaged arthritic cartilage was assessed in vitro by immunostaining articular cartilage from RA and OA patients and from normal controls. The in vivo targeting potential was tested using mice with antigen-induced arthritis, in which localization of anti,ROS-modified CII scFv in the joints was determined. The therapeutic effect of anti,ROS-modified CII scFv fused to soluble murine tumor necrosis factor receptor II,Fc fusion protein (mTNFRII-Fc) was also investigated. Results The anti,ROS-modified CII scFv bound to damaged arthritic cartilage from patients with RA and OA but not to normal preserved cartilage. When systemically administered to arthritic mice, the anti,ROS-modified CII accumulated selectively at the inflamed joints. Importantly, when fused to mTNFRII-Fc, it significantly reduced inflammation in arthritic mice, as compared with the effects of mTNFRII-Fc alone or of mTNFRII-Fc fused to an irrelevant scFv. Conclusion Our findings indicate that biologic therapeutics can be targeted specifically to arthritic joints and suggest a new approach for the development of novel treatments of arthritis. [source] Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studiesARTHRITIS & RHEUMATISM, Issue 3 2009Elizabeth W. Karlson Objective To examine the association of biomarkers of inflammation with preclinical rheumatoid arthritis (RA). Methods A nested case,control study was performed using samples from 2 large, prospectively studied cohorts of women (the Women's Health Study [WHS] and the Nurses' Health Study [NHS]). Blood samples obtained prior to symptom onset in women who later developed RA were selected as incident RA cases, and 3 controls per case were randomly chosen, matched for age, menopausal status, postmenopausal hormone use, and day, time, and fasting status at the time of collection. Plasma was tested for levels of interleukin-6 (IL-6), soluble tumor necrosis factor receptor II (sTNFRII) (as a proxy for TNF,), and high-sensitivity C-reactive protein. Relationships between biomarkers and RA were assessed using conditional logistic regression models, adjusting for age, body mass index, smoking habits, ethnicity, and reproductive factors. Results In 93 incident cases in the NHS and 77 incident cases in the WHS, the mean time between blood collection and the onset of RA symptoms was 5.2 years (range 0.3,12 years). Median IL-6 and sTNFRII levels were significantly higher in preclinical RA cases compared with matched controls in the NHS (P = 0.03 and P = 0.003, respectively) though not in the WHS. Pooled analysis of the NHS and WHS cohorts demonstrated significant association of sTNFRII with RA (relative risk 2.0 [95% confidence interval 1.1,3.6], P for trend = 0.004), and a modest association of IL-6 with RA (relative risk 1.4 [95% confidence interval 0.8,2.5], P for trend = 0.06). Conclusion Levels of sTNFRII, a biomarker typically associated with active RA, were elevated up to 12 years prior to the development of RA symptoms and were positively associated with incident RA in these nested case,control studies. Studies with repeated assessments of biomarkers prior to RA development may provide further insight into the timing of biomarker elevation in preclinical RA. [source] 4411: Immunohistochemical methods to evaluate vitreoretinal scaringACTA OPHTHALMOLOGICA, Issue 2010ML BOCHATON-PIALLAT Purpose Formation of scarlike epiretinal membranes (ERMs) constitutes potentially the end stage of evolution of proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR) and idiopathic vitreoretinopathy. Among various cellular populations, ERMs contain cells with contractile features typical of myofibroblasts. Myofibroblasts have been described in granulation tissue during wound healing and in practically all fibrocontractive diseases, in which they participate in the generation of isometric tension and in the synthesis of extracellular matrix components; these phenomena are in turn responsible for granulation tissue remodeling and retraction. The main marker of the myofibroblastic phenotype is the expression of alpha-SMA. The transforming growth factor-beta1 and the ED-A splice variant of cellular fibronectin, an extracellular matrix component, are key players of the complex process of myofibroblast differentiation. Methods Proteins were detected by means of immunohistochemical staining on paraffin sections from formol fixed tissues and double immunofluorescence staining on whole tissues. Samples were observed by using classical light and confocal microscopes. Results The presence of alpha-SM actin-positive myofibroblasts was associated with the expression of TGF-beta1, TGF-beta receptor II, and ED-A FN in all types of ERMs studied. Conclusion The results furnish new data on the mechanism of alpha-SM actin stimulation in fibroblasts in a human pathologic setting. [source] Increased expression of Fc, receptors II and III on macrophages of rheumatoid arthritis patients results in higher production of tumor necrosis factor , and matrix metalloproteinaseARTHRITIS & RHEUMATISM, Issue 4 2003Arjen B. Blom Objective To evaluate Fc, receptor (Fc,R) expression on synovial macrophages from rheumatoid arthritis (RA) patients and to determine whether this expression correlates with the production of the proinflammatory cytokines tumor necrosis factor , (TNF,), interleukin-1, (IL-1,), IL-12, and matrix metalloproteinase 1 (MMP-1). We also sought to determine whether mature macrophages from RA patients express aberrant levels of Fc,RI, Fc,RII, and Fc,RIII, and to determine the production of inflammatory mediators after immune complex (IC) stimulation. Methods Immunohistochemistry was performed on cryostat sections of synovial biopsy specimens obtained from 27 RA patients and 5 controls. Fc,R I, II, and III were detected, as well as the proinflammatory mediators IL-1, TNF,, IL-12, and MMP-1. Monocytes were isolated from the blood of 10 RA patients and 10 healthy controls and cultured for 7 days with macrophage colony-stimulating factor to obtain macrophages. Using fluorescence-activated cell sorting, the expression of Fc,RI, Fc,RII, and Fc,RIII was determined. On day 7, macrophages were stimulated with heat-aggregated gamma globulins (HAGGs) for 24 hours. Production of cytokines was measured using enzyme-linked immunosorbent assay, and production of gelatinases/collagenases was measured by degradation of fluorescent gelatin. Results Immunohistochemistry showed higher Fc,RII and Fc,RIII expression in RA synovium than in controls. Fc,RII and Fc,RIII, but not Fc,RI, were highly correlated with the number of synovial macrophages. Consistent with this, TNF, expression correlated positively with Fc,RIII expression. Moreover, MMP-1 expression strongly correlated with Fc,R I, II, and III expression. Mature macrophages from RA patients showed significantly enhanced expression of Fc,RII and Fc,RIII compared with controls. Twenty-four hours after stimulation of RA macrophages with HAGGs, significantly higher production of TNF, and gelatinase/collagenase was measured. Conclusion RA synovium and mature RA macrophages express significantly elevated levels of Fc,RII and Fc,RIII, resulting in much higher production of TNF, and gelatinase/collagenase after IC stimulation. These data suggest that disturbed expression of Fc,R on mature synovial macrophages is involved in the pathology of RA. [source] | ||||||||||