Original

The Journal of the Korean Rheumatism Association 2004; 11(2): 133-142

Published online June 30, 2004

© Korean College of Rheumatology

배양된 류마티스 활액 단핵세포 및 활막 섬유아세포에서 Vascular Endothelial Growth Factor의 자극에 의한 Tumor Necrosis Factor-α와 Interleukin-6 생성의 증가

고혁재·유승아·우성용·김해림·조철수·김완욱

가톨릭대학교 의과대학 내과학교실 류마티스 내과

Vascular Endothelial Growth Factor Stimulates Productions of Tumor Necrosis Factor-α and Interleukin-6 from Mononuclear Cells and Synoviocytes of Rheumatoid Arthritis Patients

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

Abstract

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

Article

Original

The Journal of the Korean Rheumatism Association 2004; 11(2): 133-142

Published online June 30, 2004

Copyright © Korean College of Rheumatology.

배양된 류마티스 활액 단핵세포 및 활막 섬유아세포에서 Vascular Endothelial Growth Factor의 자극에 의한 Tumor Necrosis Factor-α와 Interleukin-6 생성의 증가

고혁재·유승아·우성용·김해림·조철수·김완욱

가톨릭대학교 의과대학 내과학교실 류마티스 내과

Vascular Endothelial Growth Factor Stimulates Productions of Tumor Necrosis Factor-α and Interleukin-6 from Mononuclear Cells and Synoviocytes of Rheumatoid Arthritis Patients

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

Abstract

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

JRD
Jan 01, 2025 Vol.32 No.1, pp. 1~7
COVER PICTURE
Cumulative growth of rheumatology members and specialists (1980~2024). Cumulative distribution of the number of the (A) Korean College of Rheumatology members and (B) rheumatology specialists. (J Rheum Dis 2025;32:63-65)

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