Resveratrol inhibits TNF-α-induced IL-1β, MMP-3 production in human rheumatoid arthritis fibroblast-like synoviocytes via modulation of PI3kinase/Akt pathway

被引：139
作者：
Tian, Jing [1 ]
Chen, Jin-wei [1 ]
Gao, Jie-sheng [1 ]
Li, Len [1 ]
Xie, Xi [1 ]
机构：
[1] Cent S Univ, Xiang Ya Hosp 2, Dept Rheumatol & Immunol, Changsha 410011, Hunan, Peoples R China
来源：
RHEUMATOLOGY INTERNATIONAL | 2013年 / 33卷 / 07期
关键词：
Resveratrol; Rheumatoid arthritis; Fibroblast-like synoviocytes; Cytokines; PI3K/Akt; PHOSPHOINOSITIDE; 3-KINASE; SYNOVIAL FIBROBLASTS; INFLAMMATORY ARTHRITIS; APOPTOSIS; ACTIVATION; PI3K-GAMMA; DISEASES; THERAPY; GROWTH; AGENT;
D O I：
10.1007/s00296-012-2657-0
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Resveratrol (trans-3,4'-trihydroxystilbene), a natural phytoalexin, possesses anti-inflammatory, anti-proliferative, and immunomodulatory properties and has the potential for treating inflammatory disorders. The present study was designed to investigate the effects of resveratrol on TNF-alpha-induced inflammatory cytokines production of IL-1 beta and MMP3 in Rheumatoid arthritis (RA) Fibroblast-like synoviocytes (FLS) and further to explore the role of PI3K/Akt signaling pathway by which resveratrol modulates those cytokines production. The levels of IL-1 beta, MMP-3 in cultural supernatants among groups were measured by enzyme-linked immunosorbent assay. Messenger RNA expression of IL-1 beta and MMP-3 in RA FLS was analyzed using a reverse transcription-polymerase chain reaction. Western blot analysis was used to detect proteins expression in RA FLS intervened by resveratrol. Resveratrol inhibited both mRNA and proteins expressions of IL-1 beta and MMP-3 on RA FLS in a dose-dependent manner. Resveratrol also decreased significantly the expression of phosphorylated Akt dose dependently. Activation of PI3K/Akt signaling pathway exists in TNF-alpha-induced production of IL-1 beta and MMP3 on RA FLS, which is hampered by PI3K inhibitor LY294002. Immunofluorescence staining showed that TNF-alpha alone increased the production of P-Akt, whereas LY294002 and 50 mu M resveratrol suppressed the TNF-alpha-stimulated expression of P-Akt. Resveratrol attenuates TNF-alpha-induced production of IL-1 beta and MMP-3 via inhibition of PI3K-Akt signaling pathway in RA FLS, suggesting that resveratrol plays an anti-inflammatory role and might have beneficial effects in preventing and treating RA.
引用
收藏
页码：1829 / 1835
页数：7
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