Inhibition of Vascular Endothelial Growth Factor Expression in Cultured Rheumatoid Synoviocytes by Nonsteroidal Anti-inflammatory Drugs / 대한류마티스학회지

ABSTRACT

OBJECTIVE: Vascular endothelial growth factor (VEGF),a potent angiogenic, permeability-enhancing cytokine plays an important role in chronic inflammatory process of rheumatoid arthritis (RA).Nonsteroidal anti-inflammatory drugs (NSAIDs)are the most widely used drugs for the treatment of RA.However, the effect of NSAIDs on angiogenesis in rheumatoid synovium is unclear.In this study,we investigated the effects of NSAIDs such as indomethacin (IDC) on TGF-beta-induced VEGF production in rheumatoid synoviocytes. METHODS: Fibroblast-like synoviocytes (FLS)from RA were stimulated with T G F -beta(10 ng/ml)for 24hr in the presence of the various concentrations of IDC. The levels of VEGF were measured in culture supernatant by ELISA.In addition, COX-2 and VEGF mRNA expression of cultured FLS were evaluated by RT-PCR. RESULTS:VEGF production from FLS was significantly increased in the presence of TGF-beta.IDC exerted a dose-dependent inhibitory effect on the production of VEGF induced by TGF-beta.RT-PCR analysis showed that IDC also inhibited TGF-beta-induced COX-2 and VEGF mRNA expression in cultured FLS by a dose-dependent manner. CONCLUSION:Our results demonstrate that NSAIDs inhibit VEGF production and the expression of its mRNA and COX-2 mRNA in synovial cells of RA patients.These findings suggest that NSAIDs may suppress progression and perpetuation of rheumatoid synovitis by anti-angiogenic activity.