IL-10 Inihibits VEGF Production in the Synovial Fibroblasts of RA Patients via Down-regulation of the ERK and AP-1 Pathways

Objective: Interleukin (IL)-10 has been demonstrated to have anti-inflammatory and anti-tumour activity. Because aberrant angiogenesis is a significant pathogenic component of tumor growth and chronic inflammation, we investigated the effect of IL-10 on the production of vascular endothelial growth factor (VEGF) by the synovial fibroblasts derived from the patients with rheumatoid arthritis (RA). Methods: Fibroblast-like synoviocytes (FLS) were cultured with transforming growth factor (TGF-β) alone or with IL-10. The level of VEGF was measured by RT-PCR and enzyme-linked immunosorbent assay (using the 24, 48 and 72 h culture supernatants). The FLSs were cultured with TGF-b for 48 hr in the presence of PD98059 (an ERK inhibitor), curcumin and SP600125 (a JNK and Ap-1 inhibitor, respectively). The level of VEGF in the supernatants was measured by ELISA. Cell viability was assessed using MTT assay. The expressions of VEGF, ERK, AP-1 and IL-10 in the synovial tissue were quantified by immunohistochemistry. Results: IL-10 exhibited the inhibitory effect on VEGF production when the FLSs were stimulated with TGF-β. ERK and AP-1 inhibitors inhibited the TGF-β induced VEGF production.