白细胞介素12诱导T细胞凋亡对Bcl-2表达和信号分子的影响

目的:了解和探讨白细胞介素12(IL-12)作用于T细胞,活化T细胞表面的IL-12受体β,诱导T细胞凋亡对Bcl-2表达和信号转导的作用。方法:用AnnexinV流式细胞仪检测细胞凋亡率和半定量PCR的方法测定在不同抑制剂作用下对Bcl-2信号转导表达的影响。结果:IL-12在高浓度下诱导人的白血病T细胞株TIB-152和人的淋巴瘤T细胞株HTB-176及正常人T细胞的凋亡。在IL-12处理6h后Bcl-2的表达明显升高,表达的高峰值在24h,Bcl-2的升高不能抑制和阻碍T细胞的凋亡;IL-12诱导上调T细胞Bcl-2mRNA表达。HA100能促进T细胞的凋亡,PKC是IL-12诱导T细胞凋亡信号转导的负性调节因子;AG490不抑制IL-12上调的Bcl-2mRNA表达作用,AG490阻断的Jak2通路不参与IL-12诱导T细胞mRNA表达的信号转导及其调节;HA1004不影响T细胞表达mRNA,PKA通路不影响IL-12诱导T细胞表达Bcl-2mRNA的信号传递。结论:Bcl-2是凋亡介导分子之一,但是Bcl-2不能阻断Fas-FasL介导的T细胞凋亡。

IL-12 induces T lymphocytes underging apoptosis and affects the expression and signal conduction of Bcl-2

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 conduction of Bcl-2 during T cell apoptosis. METHODS: The apoptosis of T cells was detected by Annexin V staining cytometry and the expression of Bcl-2 under different inhibitors were detected by the method of semi-quantitative PCR. RESULTS: IL-12 can induce 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 Bcl-2 expression at 6 hours of treatment with IL-12 increased aparently, and reached the max at 24 hours. But IL-12 did influence Bcl-2 expression. IL-12 can induce T cells to undergo apoptosis which is characterized by early membrane changes. CONCLUSION: The inducing effect is correlated with the concentration of IL-12 and the maturation of T cells. Bcl-2 takes part in the progression of T cells' apoptosis as a apoptosis mediator.