磷酸鞘胺醇调节小鼠单核巨噬细胞炎性细胞因子表达的机制研究

Regulation of inflammatory cytokine expression of sphingosine 1-phosphate in murine monocyte/macrophage J774A.1

目的本课题探究了磷酸鞘胺醇(sphingosine 1-phosphate,S1P)对小鼠单核巨噬细胞J774A.1表达炎性细胞因子的调节机制。方法应用蛋白印迹实验检测小鼠单核巨噬细胞J774A.1是否表达S1P受体,进一步应用实时荧光定量聚合酶链反应检测小鼠单核巨噬细胞J774A.1在S1P刺激下是否表达炎性细胞因子,最后应用药理学工具干预S1P受体(S1P receptor,S1PRs)信号系统研究小鼠单核巨噬细胞J774A.1表达炎性细胞因子的调节机制。结果 S1PR2拮抗剂(JTE-013)、S1PR3拮抗剂(CAY-10444)可抑制小鼠单核巨噬细胞系J774A.1炎性细胞因子的表达;而S1PR1拮抗剂(W146)对小鼠单核巨噬细胞炎性细胞因子的表达并无影响。结论磷酸鞘胺醇通过S1PR2和S1PR3上调小鼠单核巨噬细胞J774A.1炎性细胞因子的表达。

Objective The aim of study is to explore the role of sphingosine 1-phosphate（ S1P） signaling on murine monocyte/macrophage inflammatory cytokine expression. Methods Western blotting was employed to test whether S1 P receptors（ S1PRs）expression in murine monocyte / macrophages. Then we detected whether S1P-mediated expression of inflammatory cytokines in murine monocyte / macrophage J774 A. 1 by real-time PCR. We studied regulatory mechanisms of expression of inflammatory cytokines in J774 A. 1cells by intervention of S1 P / S1 PRs signaling with pharmacology tools. Results S1PR2 antagonist JTE-013,S1PR3 antagonist CAY-10444 treatment reduced expression of inflammatory cytokines in J774 A. 1 cells. S1PR1 antagonist W146 has no effects on the expression of inflammatory cytokines in J774 A. 1 cells. Conclusion S1 P up-regulates expression of inflammatory cytokines in J774 A. 1 cells mediated by S1PR2 and S1PR3.