Vascular Endothelial Growth Factor Stimulates Productions of Tumor Necrosis Factor-alpha and Interleukin-6 from Mononuclear Cells and Synoviocytes of Rheumatoid Arthritis Patients.
- Author:
Hyeok Jae KO
1
;
Seung Ah YOO
;
Seong Yong WOO
;
Hae Rim KIM
;
Chul Soo CHO
;
Wan Uk KIM
Author Information
1. Department of Internal Medicine, Division of Rheumatology, Colloge of Medicine, The Catholic University of Korea, Seoul, Korea. wan725@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
VEGF;
TNF-alpha;
IL-6;
Monocytes;
Rheumatoid arthritis
- MeSH:
Angiogenesis Inducing Agents;
Arthritis, Rheumatoid*;
Dexamethasone;
Enzyme-Linked Immunosorbent Assay;
Flow Cytometry;
Humans;
Interleukin-6*;
Monocytes;
Synovial Fluid;
Tumor Necrosis Factor-alpha*;
Vascular Endothelial Growth Factor A*
- From:The Journal of the Korean Rheumatism Association
2004;11(2):133-142
- CountryRepublic of Korea
- Language:Korean
-
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. MEHTODS: Mononuclear cells and/or synoviocytes of RA patients were cultured in the presence of VEGF, and the levels of TNF-alpha and IL-6 were determined in the culture supernatants by ELISA. The TNF-alpha-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-alpha 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-alpha 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-alpha 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-alpha and IL-6.
