The Journal of the Korean Rheumatism Association 2004; 11(2): 133-142
Published online June 30, 2004
© Korean College of Rheumatology
고혁재·유승아·우성용·김해림·조철수·김완욱
가톨릭대학교 의과대학 내과학교실 류마티스 내과
Correspondence to : Wan-Uk Kim
Objective: Vascular endothelial growth factor (VEGF), an angiogenic factor, has been suggested to play a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated whether VEGF would directly regulate the activation of mononuclear cells of RA patients. Methods: Mononuclear cells and/or synoviocytes of RA patients were cultured in the presence of VEGF, and the levels of TNF-α and IL-6 were determined in the culture supernatants by ELISA. The TNF-α-or IL-6-producing cells were also assessed by flow cytometry analysis. Blocking experiments were performed by adding anti-VEGF receptor (anti-Flt-1) mAb to the cells, stimulated with VEGF. Results: VEGF directly increased the productions of TNF-α and IL-6 from peripheral blood mononuclear cells (PBMC) from healthy controls. Treatment of PBMC with anti-VEGF receptor (anti-Flt-1) mAb blocked the VEGF-induced productions of TNF-α and IL-6, suggesting that VEGF activates the PBMC via a receptor (Flt-1) coupling event. Synovial fluid mononuclear cells (SFMC) of RA patients showed a greater response to VEGF stimulation than the PBMC of healthy controls. The major cell types responding to VEGF were monocytes and synoviocytes. In addition, dexamethasone completely abrogated VEGF- stimulated productions of TNF-α and IL-6 from adherent cells, isolated from SFMC. Conclusion: Our data suggest that VEGF may directly activate RA monocytes and synoviocytes to produce TNF-α and IL-6.
Keywords VEGF, TNF-α, IL-6, Monocytes, Rheumatoid arthritis
The Journal of the Korean Rheumatism Association 2004; 11(2): 133-142
Published online June 30, 2004
Copyright © Korean College of Rheumatology.
고혁재·유승아·우성용·김해림·조철수·김완욱
가톨릭대학교 의과대학 내과학교실 류마티스 내과
Hyeok-Jae Ko, M.D., Seung-Ah Yoo, M.S., Seong-Yong Woo, M.D., Hae-Rim Kim, M.D., Chul-Soo Cho, M.D., Wan-Uk Kim, M.D.
Department of Internal Medicine, Division of Rheumatology, Colloge of Medicine, The Catholic University of Korea, Seoul, Korea
Correspondence to:Wan-Uk Kim
Objective: Vascular endothelial growth factor (VEGF), an angiogenic factor, has been suggested to play a critical role in the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated whether VEGF would directly regulate the activation of mononuclear cells of RA patients. Methods: Mononuclear cells and/or synoviocytes of RA patients were cultured in the presence of VEGF, and the levels of TNF-α and IL-6 were determined in the culture supernatants by ELISA. The TNF-α-or IL-6-producing cells were also assessed by flow cytometry analysis. Blocking experiments were performed by adding anti-VEGF receptor (anti-Flt-1) mAb to the cells, stimulated with VEGF. Results: VEGF directly increased the productions of TNF-α and IL-6 from peripheral blood mononuclear cells (PBMC) from healthy controls. Treatment of PBMC with anti-VEGF receptor (anti-Flt-1) mAb blocked the VEGF-induced productions of TNF-α and IL-6, suggesting that VEGF activates the PBMC via a receptor (Flt-1) coupling event. Synovial fluid mononuclear cells (SFMC) of RA patients showed a greater response to VEGF stimulation than the PBMC of healthy controls. The major cell types responding to VEGF were monocytes and synoviocytes. In addition, dexamethasone completely abrogated VEGF- stimulated productions of TNF-α and IL-6 from adherent cells, isolated from SFMC. Conclusion: Our data suggest that VEGF may directly activate RA monocytes and synoviocytes to produce TNF-α and IL-6.
Keywords: VEGF, TNF-α, IL-6, Monocytes, Rheumatoid arthritis
Joong Kyung Ahn, M.D., Chan Hong Jeon, M.D., Jae Hyun Koh, M.D., Jin-Hee Kim*, Hwa-Jung Choi*, Kwang-Sung Ahn, Ph.D.*, Hoon-Suk Cha, M.D., Suk Hee Yu, M.D.**, Eun-Mi Koh, M.D.
The Journal of the Korean Rheumatism Association 2003; 10(1): 30-38Byeongzu Ghang, M.D., Ph.D., Jin Kyun Park, M.D., Ph.D., Ji Hyeon Ju, M.D., Ph.D., Seungwoo Han, M.D., Ph.D.
J Rheum Dis -0001; ():Shohei Anno, M.D., Kentaro Inui, M.D., Ph.D., Masahiro Tada, M.D., Ph.D., Yuko Sugioka, M.D., Ph.D., Tadashi Okano, M.D., Ph.D.,, Kenji Mamoto, M.D., Ph.D., Tatsuya Koike, M.D., Ph.D.
J Rheum Dis -0001; ():