IL-10 Inihibits VEGF Production in the Synovial Fibroblasts of RA Patients via Down-regulation of the ERK and AP-1 Pathways.
10.4078/jkra.2009.16.3.213
- Author:
Seon Yeong LEE
1
;
Mi La CHO
;
Mi Kyung PARK
;
Hye Jwa OH
;
Sung Hwan PARK
;
Ho Youn KIM
Author Information
1. Rheumatism Research Center, Catholic Institutes of Medical Science, The Catholic University of Korea, College of Medicine, Seoul, Korea. iammila@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
IL-10;
VEGF;
ERK;
AP-1;
Rheuamtoid arthritis synovial fibroblast
- MeSH:
Anthracenes;
Arthritis, Rheumatoid;
Cell Survival;
Curcumin;
Down-Regulation;
Enzyme-Linked Immunosorbent Assay;
Fibroblasts;
Flavonoids;
Humans;
Immunohistochemistry;
Inflammation;
Interleukin-10;
Interleukins;
Phosphorylation;
Transcription Factor AP-1;
Transforming Growth Factor beta;
Transforming Growth Factors;
Vascular Endothelial Growth Factor A
- From:The Journal of the Korean Rheumatism Association
2009;16(3):213-222
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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-beta) 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-beta. ERK and AP-1 inhibitors inhibited the TGF-beta induced VEGF production. Moreover, TGF-beta 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.
