Regulation of BAFF expression by HIF-1α in synoviocytes stimulated with TNF-α : RegulationofBAFF expression byHIF-1α insynoviocytes stimulatedwithTNF-α
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Rheumatoid arthritis (RA) is autoimmune disease that accompanies excessive expansion of synovium. Fibroblast-like synoviocytes (FLS) which located in synovium is in charge of the progression of RA. Inflammatory cytokines, TNF-α induces B cell activating factor in FLS and it could regulate RA angiogenesis. TNF-α also could up-regulate HIF-1α expression even under normoxic conditions. Here, we investigated whether BAFF could be regulated by TNF-α mediated HIF-1α up-regulation in MH7A synovial cells. When MH7A cells were treated with TNF-α, enhanced levels of BAFF expression and HIF-1α were judged by western blotting, and RT-PCR. TNF-α-induced BAFF expression was decreased by the inhibition of HIF-1α expression with HIF-1α-siRNA. In addition, BAFF expression was increased in hypoxia condition. We examined signal transduction to control HIF-1α-mediated BAFF expression. TNF-α induced ERK phosphorylation. Treatment of PD98059, ERK inhibitor, reduced HIF-1α and BAFF expression. Collectively, our results demonstrate that BAFF expression could be regulated by HIF-1α.