J Korean Rheum Assoc.
2001 Dec;8(4):253-261.
Inhibition of Vascular Endothelial Growth Factor Expression in Cultured Rheumatoid Synoviocytes by Nonsteroidal Anti-inflammatory Drugs
- Affiliations
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- 1Division of Rheumatology, Kangnam St. Mary's hospital, The Catholic University of Korea, Korea. rheuma@cmc.cuk.ac.kr
- 2Catholic Research Institutes of Medical Sciences, Korea.
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.
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