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Tumor Necrosis Factor-a Induces Vascular Endothelial Growth Factor-C Expression in Rheumatoid Synoviocytes
HOON-SUK CHA, EUN-KYUNG BAE, JAY-HYUN KOH, JI-YOUNG CHAI, CHAN HONG JEON, KWANG-SUNG AHN, JINSEOK KIM, and EUN-MI KOH ABSTRACT. 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-a (TNF-a), and interleukin 1ß (IL-1ß) 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-a or IL-1ß, 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-a and IL-1ß in the synovial fluid of patients with RA. TNF-a 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-1ß stimulation in FLS. Conclusion. Overexpression of VEGF-C in FLS by stimulation with TNF-a may play an important role in the progression of synovial inflammation and hyperplasia in RA by contributing to local lymphangiogenesis and angiogenesis. (J Rheumatol 2007;34:16–19) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Supported by the Korea Science and Engineering Foundation (R01-2004-000-11007-0). H.S. Cha, MD, Associate Professor; J.H. Koh, MD; J.Y. Chai, MD; C.H. Jeon, MD; E.M. Koh, MD, Associate Professor, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; E.K. Bae, MS; K.S. Ahn, PhD, Center for Molecular Medicine, Samsung Biomedical Research Institute; J. Kim, MD, Assistant Professor, Department of Internal Medicine, College of Medicine, Cheju National University, Jeju-do, Korea. Address reprint requests to Dr. E.M. Koh, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul 135-710, Korea. E-mail: eunmi.koh@samsung.com Accepted for publication August 1, 2006. |
