Yu Dan, Ye Xianlong, Che Ruixiang, Wu Qiang, Qi Jianying, Song Liying, Guo Xiaochen, Zhang Shengqi, Wu Hongsong, Ren Guiping, Li Deshan
Biopharmaceutical Lab, College of Life Science, Northeast Agricultural University, Harbin 150030, China.
College of Life Science, Henan Normal University, Xinxiang 453007, China.
Biomed Pharmacother. 2017 May;89:751-760. doi: 10.1016/j.biopha.2017.02.059. Epub 2017 Mar 6.
Previous studies have reported that Fibroblast growth factor 21 (FGF21) can regulate inflammation and may play an important role in inflammatory and immune-mediated diseases, such as autoimmune diseases. Adalimumab is one of the clinically effective anti-rheumatoid arthritis (RA) drugs. The aim of this study was to compare the therapeutic efficacy of FGF21 and Adalimumab on collagen-induced arthritis (CIA) model mice. Mice with CIA were subcutaneously treated with FGF21 or Adalimumab at dose of 1mgkgd, respectively. Our results showed that FGF21 significantly alleviated the severity of arthritis by reducing cellular immune responses and exerted the similar anti-inflammatory effects with Adalimumab in decreasing the mRNA and protein expression levels of IL-2, IL-6 and IL-17. However, the expression levels of IL-1β, RANKL and IL-10 in the mice treated with FGF21 were decreased 2.2-fold, 2.5-fold and increased 4.3-fold compared with Adalimumab, respectively. However, the levels of TNF-α in the mice treated with Adalimumab were lower than those in the mice treated with FGF21. Western blotting results demonstrated that FGF21 displayed equivalent effects with Adalimumab by inhibiting NF-κB/IκBα signaling pathway. However, FGF21 could also regulate systematic inflammatory response and the mechanism maybe related to other signal pathway. In summary, FGF21 exerts comparable pharmacological efficacy with Adalimumab by regulating systematic inflammatory response, providing that FGF21 may be a promising therapeutic agent for RA patients.
先前的研究报道,成纤维细胞生长因子21(FGF21)可调节炎症,可能在炎症和免疫介导的疾病(如自身免疫性疾病)中发挥重要作用。阿达木单抗是临床上治疗类风湿性关节炎(RA)的有效药物之一。本研究旨在比较FGF21和阿达木单抗对胶原诱导性关节炎(CIA)模型小鼠的治疗效果。将患有CIA的小鼠分别以1mg/kg/d的剂量皮下注射FGF21或阿达木单抗。我们的结果表明,FGF21通过降低细胞免疫反应显著减轻了关节炎的严重程度,并且在降低IL-2、IL-6和IL-17的mRNA和蛋白表达水平方面与阿达木单抗具有相似的抗炎作用。然而,与阿达木单抗相比,用FGF21治疗的小鼠中IL-1β、RANKL和IL-10的表达水平分别降低了2.2倍、2.5倍和升高了4.3倍。然而,用阿达木单抗治疗的小鼠中TNF-α的水平低于用FGF21治疗的小鼠。蛋白质印迹结果表明,FGF21通过抑制NF-κB/IκBα信号通路与阿达木单抗发挥等效作用。然而,FGF21也可以调节全身炎症反应,其机制可能与其他信号通路有关。总之,FGF21通过调节全身炎症反应发挥与阿达木单抗相当的药理作用,提示FGF21可能是RA患者一种有前景的治疗药物。