The antiinflammatory

The antiinflammatory Tenatoprazole? role of HDL has been widely described in in vitro as well as in in vivo models of athero sclerosis. In addition, HDL associated apo AI dis play antiinflammatory effects in other inflammatory disorders in which T cell contact induced cytokines produc tion in monocytes Inhibitors,Modulators,Libraries macrophages is likely to play a part. HDL also potently reduce radical oxygen species production induced in neutrophils on contact with stimu lated T cells. Recently we demonstrated that apo A I, HDL, and total cholesterol levels are decreased in plasma, whereas apo A I is increased in the synovial fluid of patients with inflammatory arthritis. The correlation between synovial fluid serum apo A I ratio and both local and systemic inflammatory indexes suggests the involve ment of HDL in the synovial inflammatory process.

The mechanisms of HDL antiinflammatory effects were partly identified. For instance, HDL might hamper the bind ing of LPS to its receptor at the cell surface, as reviewed by Wu et al. Similarly, it is likely that HDL impede the interaction between stimulated T cells and monocytes. Here we demonstrate that HDL display antiinflammatory properties Inhibitors,Modulators,Libraries in MSU crystal induced inflammation by decreasing the production and expression of CCL2 in Conclusions The present results demonstrate that MSU crystals induce FLS to release CCL2 that is stored in vesicles in resting conditions. This mechanism is inhibited by HDL, which may limit the inflammatory process by diminishing CCL2 production and, in turn, monocytes macrophages recruit ment in joints.

Although further studies are needed to iden tify which signal transduction pathways are specifically involved in the activation of FLS by MSU crystals and to elucidate the mechanism of action of HDL in the limitation of crystal induced inflammation, this study confirms the antiinflammatory Inhibitors,Modulators,Libraries functions of HDL, which might contrib ute to the resolution of acute gout Inhibitors,Modulators,Libraries attack. Introduction Expression of the regulatory peptides, platelet derived growth factor and transforming growth factor beta are increased in synovial tissue and fluid of rheumatoid arthritis patients. PDGF has been implicated in RA pathogenesis, mainly through its func tion as a growth factor for fibroblast like synoviocytes. In contrast, the actions of TGF B are more complex. TGF B plays a crucial role in maintaining immunological tolerance through the inhibition of lym phocytes Inhibitors,Modulators,Libraries and macrophages. On the other hand, it recruits and activates naive monocytes, stimulates proliferation and induces aggrecanase synthesis by FLS. Systemic administration of TGF B protects against development of collagen arthritis in mice, whereas direct EPZ-5676 mw injection of TGF B into rat joints leads to pro nounced synovitis.

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