TY - JOUR T1 - Tumor necrosis factor-alpha induces vascular endothelial growth factor-C expression in rheumatoid synoviocytes. JF - The Journal of Rheumatology JO - J Rheumatol SP - 16 LP - 19 VL - 34 IS - 1 AU - Hoon-Suk Cha AU - Eun-Kyung Bae AU - Jay-Hyun Koh AU - Ji-Young Chai AU - Chan Hong Jeon AU - Kwang-Sung Ahn AU - Jinseok Kim AU - Eun-Mi Koh Y1 - 2007/01/01 UR - http://www.jrheum.org/content/34/1/16.abstract N2 - OBJECTIVE: To determine the expression of vascular endothelial growth factor-C (VEGF-C) in the synovial fluid of patients with rheumatoid arthritis (RA) and to investigate the regulation of VEGF-C production by major proinflammatory cytokines in fibroblast-like synoviocytes (FLS). METHODS: The concentrations of VEGF-C, tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta) were measured using an ELISA method in synovial fluids obtained from 20 patients with RA and 20 with osteoarthritis (OA). Primary cultured RA FLS were stimulated with TNF-alpha or IL-1beta, and the expression levels of VEGF-C mRNA and protein were assessed by quantitative real-time polymerase chain reaction and ELISA. RESULTS: Significantly higher levels of VEGF-C were found in RA synovial fluids compared to OA synovial fluids. VEGF-C levels showed a highly significant correlation with the levels of both TNF-alpha and IL-1beta in the synovial fluid of patients with RA. TNF-alpha stimulation significantly increased VEGF-C mRNA and protein expression in RA FLS in a dose-dependent manner. A tendency to increased expression of VEGF-C was also observed after IL-1beta stimulation in FLS. CONCLUSION: Overexpression of VEGF-C in FLS by stimulation with TNF-alpha may play an important role in the progression of synovial inflammation and hyperplasia in RA by contributing to local lymphangiogenesis and angiogenesis. ER -