炎症性细胞因子IL-17A和免疫抑制细胞在DEN诱导小鼠肝癌中的作用

IL-17A and myeloid-derived suppressor cells may promote induction of hepartocellular carcinoma by 1,2-diethylnirtosamine in mice

关键词:  肝肿瘤  IL-17A  免疫抑制细胞  小鼠

Key words:  tumor of live  IL-17A  myeloid-dirived suppressor cells  mouse

摘要:

目的探讨炎症性细胞因子IL-17A及免疫抑制细胞（myeloid-derived suppressor cells,MDSC）在二乙基亚硝铵（1,2-diethylnirtosamine,DEN）诱导的小鼠肝癌模型中的作用。方法建立小鼠肝癌模型,取肝脏,实时荧光定量RT-PCR法检测IL-17A的mRNA表达;通过免疫组化法检测IL-17A的蛋白水平表达;胞内细胞因子染色法检测产生IL-17A的细胞来源;细胞表面分子染色法检测MDSC的浸润。结果肝癌小鼠中瘤内和瘤周IL-17A的mRNA表达显著高于正常小鼠,分别是正常小鼠的7.3倍和2.8倍;在肝脏局部中CD4＋T细胞、γδT细胞能产生大量的IL-17A,而CD8＋T细胞也能产生少量的IL-17A;肝癌小鼠肝脏局部浸润的M DSC要明显高于正常小鼠,M DSC在正常小鼠肝脏局部免疫细胞中分别约占1.7%,而在肝癌小鼠中达到了15.8%。结论炎症细胞因子IL-17A以及免疫抑制细胞M DSC在肝癌的病理进程中均起着非常重要的作用。

Abstract:

Objective To investigate the roles of inflammatory cytokine IL-17 A and myeloid-derived suppressor cells（ MDSCs） in 1,2-Diethylnirtosamine（ DEN）-induced hepartocellular carcinoma（ HCC） in mice. Methods HCC was induced by injection of 25 μg /g DEN intraperitoneally in C57 BL /6 mice. The expression of IL-17 A mRNA and protein in liver tissue was detected by quantitative Real-Time PCR and immunohistochemistry,respectively. The IL-17A＋cells and MDSCs in liver were examined by flow cytometry. Results Expression of IL-17 A mRNA of in HCC and pericancerous liver tissue were higher by 7. 3 and 2. 8 fold than that in normal liver tissue. IL-17 A positive-CD4＋T,γδT and CD8＋T cells were detected by cytometry in liver tissue of HCC mice. The percentage of MDSC is significantly higher in the liver of HCC mice than that of normal mice（ 15. 78% vs 1. 7%）. Conclusion The inflammatory cytokine IL-17 A and MDSC may promote the induction of HCC by DEN in mice.