J Korean Rheum Assoc.  2004 Jun;11(2):133-142.

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

• Ko HJ
• Yoo SA
• Woo SY
• Kim HR
• Cho CS
• Kim WU

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.

Keyword

VEGF; TNF-alpha; IL-6; Monocytes; Rheumatoid arthritis

MeSH Terms

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*
Angiogenesis Inducing Agents
Dexamethasone
Interleukin-6
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A