%0 Journal Article
%T Tyrosine kinases in rheumatoid arthritis
%A Hiroshi Okamoto
%A Akiko Kobayashi
%J Journal of Inflammation
%D 2011
%I BioMed Central
%R 10.1186/1476-9255-8-21
%X Rheumatoid arthritis (RA) is a destructive, inflammatory, polyarticular joint disease with an etiology that remains to be fully elucidated. RA is characterized by massive synovial proliferation and subintimal infiltration of inflammatory cells, followed by the destruction of cartilage and bone [1]. A number of cellular responses are involved in the pathogenesis of RA, including activation of inflammatory cells and expression of various cytokines. Macrophages, T cells, B cells and neutrophils migrate into synovial tissue and activate these cells to produce both inflammatory and degradative mediators that break down the extracellular matrix of cartilage. Synovial cells undergo hyperplasia, and angiogenesis occurs in synovial tissues further promoting inflammation. Although synoviocyte proliferation contributes to the hyperplastic response of synovial tissue in RA, synovial tissue hyperplasia must also be a result of the recruitment, retention and attachment of mast cells, neutrophils, and lymphocytes to the inflamed tissue as well as the stimulus of neoangiogenesis. Inflammatory mediators such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor-¦Á (TNF-¦Á) play important roles in the pathogenesis of RA. These cytokines are abundant in synovial tissues and fluid from RA patients and overexpression of the cytokines mentioned above promote chronic inflammation and joint destruction [2]. These cytokines have emerged as dominant pro-inflammatory mediators and important molecular targets for therapy [3]. TNF-a and IL-1 has been reported to stimulate synovial cells to release VEGF which has important role in the angiogenesis observed in RA pathology [4,5]. Classically, immune responses are regulated by two subtypes of CD4 + T helper (Th) cells, designated Th1 and Th2. Th1 cells produce interferon- (IFN-¦Ã) and interleukin-2 (IL-2), which are known to be important mediators of organ-specific autoimmune disorders. On the other hand, Th2 cells produce the cytok
%U http://www.journal-inflammation.com/content/8/1/21