Li Si-Ming, Yu Yin-Hang, Li Lu, Wang Wen-Fei, Li De-Shan
Harbin University of Commerce, No. 1 Xuehai Street Songbei Distric, 150028, Harbin, Heilongjiang, China.
School of Life Science, Northeast Agricultural University, No. 59 Mucai Street Xiangfang Distric, 150030, Harbin, Heilongjiang, China.
Inflammation. 2016 Feb;39(1):309-319. doi: 10.1007/s10753-015-0251-9.
Recently, FGF21 was reported to play an important role in anti-inflammation. The aim of the study is to explore the mechanism for FGF21 alleviating inflammation of CIA. CIA mice were injected with FGF21 once a day for 28 days after first booster immunization. The results showed that FGF21 alleviates arthritis severity and decreases serum anti-CII antibodies levels in CIA mice. Compared with CIA model, the number of the splenic TH17 cells was significantly decreased in FGF21-treated mice. FGF21 treatment reduced the mRNA expression of IL-17, TNF-α, IL-1β, IL-6, IL-8, and MMP3 and increased level of IL-10 in the spleen tissue. The expression of STAT3 and phosphorylated STAT3 was suppressed in FGF21-treated group. The mRNA expression of RORγt and IL-23 also decreased. In conclusion, these findings suggest that the beneficial effects of FGF21 on CIA mice were achieved by down-regulating Th17-IL-17 axis through STAT3/RORγt pathway. Modulating of Th17-mediated inflammatory response may be one of the mechanisms for FGF21 attenuating inflammation in CIA.
最近，有报道称成纤维细胞生长因子21（FGF21）在抗炎过程中发挥重要作用。本研究旨在探讨FGF21减轻胶原诱导性关节炎（CIA）炎症的机制。初次加强免疫后，对CIA小鼠每天注射一次FGF21，持续28天。结果显示，FGF21可减轻CIA小鼠的关节炎严重程度，并降低血清抗Ⅱ型胶原（CII）抗体水平。与CIA模型相比，FGF21处理组小鼠脾脏辅助性T细胞17（TH17细胞）数量显著减少。FGF21处理降低了脾脏组织中白细胞介素17（IL-17）、肿瘤坏死因子-α（TNF-α）、白细胞介素1β（IL-1β）、白细胞介素6（IL-6）、白细胞介素8（IL-8）和基质金属蛋白酶3（MMP3）的mRNA表达，并提高了白细胞介素10（IL-10）水平。FGF21处理组信号转导和转录激活因子3（STAT3）及磷酸化STAT3的表达受到抑制。维甲酸相关孤儿受体γt（RORγt）和白细胞介素23（IL-23）的mRNA表达也降低。总之，这些发现表明，FGF21对CIA小鼠的有益作用是通过STAT3/RORγt途径下调Th17-IL-17轴实现的。调节Th17介导的炎症反应可能是FGF21减轻CIA炎症的机制之一。
