实用肝脏病杂志 ›› 2016, Vol. 19 ›› Issue (4): 404-407.doi: 10.3969/j.issn.1672-5069.2016.04.006

• 实验性肝炎 • 上一篇    下一篇

1,25(OH)2D3通过STAT5抑制Th17细胞分化的调控作用研究*

周鸿, 顾磊, 蒋春晖, 孙隆慈, 刘晔, 许春杰, 徐庆   

  1. 200127上海市 交通大学医学院附属仁济医院胃肠外科
  • 收稿日期:2016-01-10 出版日期:2016-07-30 发布日期:2016-08-31
  • 通讯作者: 徐庆,E-mail:renjixuqing@163.com
  • 作者简介:周鸿,男,41岁,博士研究生,主治医师。主要从事消化内镜诊断与治疗学研究 。E-mail:renjizhouhong@163.com
  • 基金资助:
    上海市卫生和计划生育委员会科研课题(编号:20154Y0207)

1,25-(OH)2D3 inhibits Th17 cell differentiation via STAT5 signaling

Zhou Hong, Gu Lei, Jiang Chunhui, et al   

  1. Department of Gastrointestinal Surgery,Renji Hospital,School of Medicine,JiaoTong University,Shanghai 200127,China
  • Received:2016-01-10 Online:2016-07-30 Published:2016-08-31

摘要: 目的 研究1.25二羟基维生素D3[1,25(OH)2D3]抑制辅助性T细胞17(Th17)的分化与STAT5调控的关系。方法 通过分选出的CD4+T细胞,在1,25(OH)2D3和/或STAT5抑制剂的作用下,采用ELISA法检测抑制剂处理后细胞培养上清液Th17细胞因子(IL-17A、IL-22)水平的变化;采用细胞免疫荧光技术检测STAT5的磷酸化水平,采用Western blot技术检测STAT5蛋白表达水平。结果 1,25(OH)2D3组细胞培养上清IL-17A和IL-22水平(12.5±0.5 ng/ml,48.5±0.9 pg/ml)明显低于对照组(22.7±0.5 ng/ml,73.8±1.9 pg/ml),而STAT5抑制剂组IL-17A和IL-22水平明显升高(33.5±0.7 ng/ml,89.1±1.4 pg/ml),1,25(OH)2D3与STAT5抑制剂联合作用细胞IL-17A和IL-22水平(18.5±0.7 ng/ml,54.1±1.6 pg/ml)显著高于1,25(OH)2D3组,但低于STAT5抑制剂组,差异有统计学意义(P<0.01);1,25(OH)2D3组细胞p-STAT5表达显著强于对照组,1,25(OH)2D3联合STAT5抑制剂组p-STAT5表达量低于对照组,而STAT5抑制剂组细胞p-STAT5表达量最低;1,25(OH)2D3组STAT5蛋白表达明显升高,而1,25(OH)2D3联合STAT5抑制剂组或STAT5抑制剂组STAT5蛋白表达明显降低,以STAT5抑制剂组细胞表达最弱,差异均具有统计学意义(P<0.01)。结论 1,25(OH)2D3通过STAT5信号通路能抑制Th17细胞分化。

关键词: 辅助性T 细胞17, 1,25-二羟基维生素D3, STAT5, 细胞分化, 小鼠

Abstract: Objective To explore the role of 1,25-(OH)2D3 in inhibiting T helper cell 17(Th17) differentiation and the role of STAT5 in this process. Methods Sorted CD4+T cells were treated with 1,25-(OH)2D3 and/or STAT5 inhibitors. The Th17 cytokines (IL-17A,IL-22) levels in supernatants were detected by ELISA;the phosphorylation level of STAT5 was examined by cell immunofluorescence,and Western blot was used to detect STAT5 protein expression. Results The levels of IL-17A and IL-22 in 1,25-(OH)2D3-treated group were significantly lower than those in the control group [(12.5±0.5) ng/ml and (22.7±0.5) pg/ml vs. (48.5±0.9) ng/ml and(73.8±1.9) pg/ml,respectively,P<0.01],while in STAT5 inhibitor-treated group had higher levels of IL-17A [(33.5±0.7) ng/ml] and IL-22 [(89.1±1.4) pg/ml,P<0.05];IL-17A [(18.5±0.7) ng/ml] and IL-22 [(54.1±1.6) pg/ml] levels in cells treated with 1,25(OH)2D3 combined with STAT5 inhibitor were significantly higher than those in 1,25-(OH)2D3-treated alone,whereas lower than those in STAT5 inhibitor-treated cells (P<0.01 for both);the expression of p-STAT5 was higher in 1,25-(OH)2D3-treated cells and lower in 1,25-(OH)2D3 combined with STAT5 inhibitor-treated cells,while in STAT5 inhibitor-treated cells had the lowest p-STAT5; the STAT5 protein expression was significantly higher in 1,25-(OH)2D3-treated cells,whereas lower in 1,25-(OH)2D3 combined with STAT5 inhibitor-treated cells or in STAT5 inhibitor-treated cells had the lowest STAT5 protein expression (P<0.01 for all). Conclusion 1,25-(OH)2D3 might inhibit Th17 cell differentiation via STAT5 signaling pathway.

Key words: T helper cell 17, 1,25-(OH)2D3, STAT5, Cell differentiation, Mice