体外抑制肿瘤JAK/STAT通路探讨STAT4对肿瘤免疫的影响  

Functional Analysis of Stat4 in Tumor Immunity by Inhibitory Jak/Stat in Vitro

作　　者：王悦[1] 李玉皓[1] 李小洁[1] 曾彬[1] 张园[1] 彭茜[1] 杨荣存[1] 

机构地区：[1]南开大学医学院,天津300071

出　　处：《南开大学学报（自然科学版）》2007年第3期102-105,共4页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：教育部留学归国科研基金(12304E14)

摘　　要：利用小 RNA 技术对肿瘤细胞系 Mosec 中 STAT4蛋白的表达进行干预,结合用干预后的肿瘤细胞培养上清液与脾细胞共培养后流式细胞分析的方法,检测 CD4+CD25+Treg 细胞被引导情况.得到了抑制肿瘤细胞 STAT4后,引导出增高比例的 CD4+CD25+Treg 细胞的结果.进一步检测培养上清液中细胞因子TGF-β2和 IL-10 mRNA 的表达,发现肿瘤细胞 STAT4蛋白表达被抑制后,IL-10分泌明显增加,而 TGF-β2没有明显改变.这一结果暗示着肿瘤细胞是通过 STAT4的激活来下调 IL-10的表达和 CD4+CD25+Treg 细胞比例,来削弱对 T 细胞增殖的抑制效应,进而增强机体对肿瘤免疫的可能性.It is known that a part of CD4＋CD25＋T cells are capable of immune suppressive activity, involving tumor immunity. In this study, using the technology of RNA interference, we examined the inducible effect of the STAT4 by inhibitory JAK/STAT on T cells in vitro by flow cytometry （FCM）in the ratio of the proportion of CD4＋CD25＋T cells. The ratio of CD4＋CD25＋T cells in co-cultured supernatant with STAT4 negative expression was higher. Furthermore, we found the levels of IL-10 mRNA of STAT4 negative expression were higher than those in normal expression in tumor cells via RT-PCR. CD4＋CD25＋T cells in the supernatant of co-cultured cells had the ability to proliferate after the stimulation with relatively high dose of IL-10. Our results suggested that the ratio of CD4＋CD25＋T cells initiated and increased by interfering the expression of STAT4 transduction signaling molecule and blockade JAK/S;FAT pathway in tumor cell lines, which were capable of tumor immune suppression activity , probably appeared through the existence of high dose of IL-10.

关 键 词：TAT4 CD4+CD25+TREG细胞 IL-10 TGF—β 

分 类 号：R392.3[医药卫生—免疫学]