IL-10 Inihibits VEGF Production in the Synovial Fibroblasts of RA Patients via Down-regulation of the ERK and AP-1 Pathways / 대한류마티스학회지
The Journal of the Korean Rheumatism Association
;
: 213-222, 2009.
Article
in Korean
| WPRIM
| ID: wpr-80927
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Arthritis, Rheumatoid
/
Flavonoids
/
Enzyme-Linked Immunosorbent Assay
/
Immunohistochemistry
/
Transforming Growth Factors
/
Down-Regulation
/
Cell Survival
/
Transforming Growth Factor beta
/
Interleukins
Limits:
Humans
Language:
Korean
Journal:
The Journal of the Korean Rheumatism Association
Year:
2009
Type:
Article
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