In the pathogenesis of RA is supported by the presence of autoantibodies

To facilitate functional genomics in the nervous system, an appropriate methodology should be taken for conditional genetic manipulation to the purpose. Our system has the potential to be a tool with which to elucidate the in vivo molecular mechanisms of later stages of development. Rheumatoid arthritis is a chronic autoimmune disease that features persistent synovial inflammation and proliferation along with infiltration of predominantly T lymphocytes, plasma cells and macrophages. A central role for the B lymphocytes in the pathogenesis of RA is supported by the presence of 4′-Chloropropiophenone autoantibodies, which are locally produced in the inflamed synovium and may promote tissue inflammation and destruction by forming immune complexes. Moreover, a significant percentage of RA patients display ectopic lymphoid structures in the synovial membrane that could sustain T and B cell interaction. Finally, effector B cells produce cytokines and other immunological mediators thereby promoting the extent and direction of immune responses. The observation that therapeutic B cell depletions using rituximab treatment disrupts synovial lymphoid neogenesis and decreases macrophages infiltration supports the notion that B cells orchestrate synovial inflammation in RA. In the rheumatoid joint, the synovial fluid contains a variety of cytokines, chemokines, growth factors and lipid-derived mediators, which potentially mediate B cells effector functions. Of the prostaglandins, high levels are reached by prostaglandin E2, which plays a prominent role in the rheumatoid Eupalinilide-D pathogenic process by promoting tissue damaging and autoimmunity. Microsomal prostaglandin E2 synthase 1 catalyses its formation from cyclooxygenase-derived PGH2 and is an inflammation-induced enzyme overexpressed in synovial tissue of RA patients. MPGES1 is mostly found in fibroblast-like synoviocytes and macrophages. Cyclooxygenase enzymes known as COX-1 and COX-2 are also widely expressed in the inflamed synovium. COX-1 is present in intimal lining layer and synovial sublining mononuclear cells and FLS. COX2 has a similar localization, but is also highly expressed by endothelial cells. Furthermore, whereas COX-1 expression is independent of the inflammatory status in the joint tissue, COX-2 is markedly upregulated at sites of inflammation.

Leave a Reply

Your email address will not be published.