Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway

文献类型： 外文期刊

第一作者： Yu, Yinhang

作者： Yu, Yinhang;Li, Siming;Liu, Yaonan;Tian, Guiyou;Yuan, Qingyan;Bai, Fuliang;Wang, Wenfei;Ren, Guiping;Li, Deshan;Wang, Wenfei;Ren, Guiping;Li, Deshan;Zhang, Yu;Zhang, Zhiyi;Li, Siming

作者机构：

关键词： Rheumatoid arthritis;Collagen-induced arthritis;FGF21;Oxidative stress;NF-kappa B;Inflammation

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.932； 五年影响因子：4.624 ）

ISSN： 1567-5769

年卷期： 2015 年 25 卷 1 期

页码：

收录情况： SCI

摘要： It has been demonstrated that circulating FGF21 levels are elevated in the serum and synovial fluid of patients with rheumatoid arthritis (RA). The aim of this study is to investigate efficacy of FGF21 for treatment of RA and the molecular mechanisms of the therapeutic effect on collagen-induced arthritis (CIA). Mice with CIA were subcutaneously administered with FGF21 (5, 2 or 1 mg.kg(-1).d(-1)), IL-1 beta antibody (5 mg.kg(-1).d(-1)), IL-17A antibody (5 mg.kg(-1).d(-1)) and dexamethasone (DEX) (1 mg.kg(-1).d(-1)), respectively. The effects of treatment were determined by arthritis severity score, histological damage and cytokine production. The activation of NF-kappa B was analyzed by Western blotting. We also detected the levels of oxidative stress parameters. Our results showed that FGF21 had beneficial effects on clinical symptom and histological lesion of CIA mice. Similar to antibody and DEX, FGF21 treatment alleviated the severity of arthritis by reducing humoral and cellular immune responses and down-regulating the expression of pro-inflammatory cytokines. FGF21 treatment also reduced the expression of TNF-alpha, IL-1 beta, IL-6, IFN-gamma and MMP-3 and increased level of IL-10 in the spleen tissue or the plasma of CIA mice in a dose-dependent manner. Furthermore, FGF21 inhibited Ma degradation and NF-kappa B p65 nuclear translocation and induced significant changes of oxidative stress parameters (MDA, SOD, CAT, GSH-PX and GSH) in the plasma. FGF21 exerts therapeutic efficacy for RA through antioxidant reaction and inhibiting NF-kappa B inflammatory pathway. This study provides evidence that FGF21 may be a promising therapeutic agent for RA patients. (C) 2015 Elsevier B.V. All rights reserved.

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