白介素12诱导T细胞凋亡时Fas/FasL表达和信号转导的研究

IL-12 induces T lymphocytes apoptosis and influences the expression and signal transduction of Fas/FasL

目的 :为了解和探讨白介素 1 2 (IL - 1 2 )作用于T细胞 ,活化T细胞表面的IL - 1 2受体 β1 / β2复合物 ,调节Th1 /Th2平衡 ,诱导T细胞凋亡时对Fas/FasL表达和信号传导的作用。方法 :用AnnexinV的方法流式细胞仪检测细胞凋亡 ;用半定量PCR的方法测定在不同抑制剂作用下对Fas/FasL信号传导的影响。结果 :IL - 1 2诱导人TIB - 1 52、HTB - 1 76和正常T细胞的凋亡 ;IL - 1 2可上调T细胞的FasLmRNA表达。在IL - 1 2作用 6h后FasL的表达明显升高 ,表达的高峰值在 2 4h。HA1 0 0抑制剂能促进T细胞的凋亡 ,PKC抑制剂是IL - 1 2诱导T细胞凋亡信号传导的负性调节因子 ;AG490抑制剂不抑制IL - 1 2上调的FasLmRNA表达作用 ,说明其阻断的Jak2通路不参与IL -1 2对FasL表达的信号传导过程 ;HA1 0 0 4不影响T细胞表达FasLmRNA。结论 :IL - 1 2能诱导TIB - 1 52、HTB - 1 76和正常人T细胞的凋亡。FasL作为介导分子参与此过程 ,IL - 1 2对T细胞FasLmRNA表达信号传递与PKC通路有关。

AIM: IL-12 acts upon T lymphocytes and activates its receptor complexes of β1/β2 ,and so IL-12 can regulate TH1/TH2 balance. Our study is aimed at IL-12-inducing apoptosis of T cells and expression and signal transduction of Fas/FasL during T cell apoptosis. METHODS: The apoptosis of T cells was detected by Annexin V staining cytometry and the expression of Fas/FasL under different inhibitors were detected by semi-quantitative PCR. RESULTS: IL-12 induced the human leukemic T cell line(TIB-152) and the human lymphoma T cell line(HTB-176) and the normal human T cells to undergo apoptosis. The FasL expression at 6 hours after treatment with IL-12 increased apparently, and reached the max at 24 hours, and FasL expression induced by IL-12 was inhibited by PKC inhibitor. But IL-12 did not influence Fas expression. CONCLUSIONS: IL-12 can induce T cells to undergo apoptosis which is characterized by early membrane changes, the inducing effect is correlated with the concentration of IL-12 and the maturation of T cells. FasL participates in the progression of T cell apoptosis as a apoptosis mediator, and the effect of IL-12 on FasL expression may be related with PKC pathway.