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KMID : 0388220090160030213
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Journal of the Korean Rheumatism Association
2009 Volume.16 No. 3 p.213 ~ p.222
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IL-10 Inihibits VEGF Production in the Synovial Fibroblasts of RA Patients via Down-regulation of the ERK and AP-1 Pathways
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Lee Seon-Yeong
Cho Mi-La
Park Mi-Kyung
Oh Hye-Jwa
Park Sung-Hwan
Kim Ho-Youn
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Abstract
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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-?) 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-?. ERK and AP-1 inhibitors inhibited the TGF-? induced VEGF production. Moreover, TGF-? increased the phosphorylation of ERK and C-Jun, which was significantly inhibited by the IL-10.
Conclusion: IL-10 may exert an antiangiogenic effect by inhibiting the ERK- and AP-1 mediated VEGF expression in rheumatoid synovial fibroblasts.
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KEYWORD
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IL-10, VEGF, ERK, AP-1, Rheuamtoid arthritis synovial fibroblast
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