IL-21通过SENP1调控NK细胞生物学特性

IL-21 modulates biological characteristics of NK92 cells by upregulating SENP1 expression

目的探讨IL-21对小泛素相关修饰蛋白特异性蛋白酶1(SENP1)表达的影响及其对NK细胞生物学特性的调控作用。方法以NK92细胞系为模型,采用慢病毒介导的Senp1基因干涉策略,抑制NK92细胞SENP1的表达。实时荧光定量PCR和Western印迹检测SENP1表达水平;利用CCK-8细胞增殖检测试剂盒测定细胞增殖活性;AnnexinⅤ-APC/PI标记检测细胞凋亡。将K562细胞与NK92细胞共培养,荧光素酶报告基因方法检测NK92细胞的杀伤活性。结果 IL-21处理上调NK92细胞SENP1的表达;慢病毒介导Senp1-shRNA转染显著降低NK92细胞内Senp1 mRNA和蛋白表达水平。Senp1干涉组NK92细胞增殖能力较对照组明显降低。同时,干涉Senp1能促进NK92细胞凋亡,但对NK92细胞杀伤K562活性无显著影响。结论 IL-21上调NK92细胞SENP1的表达;干涉Senp1能抑制NK92细胞增殖,促进细胞凋亡,同时影响穿孔素表达和对肿瘤细胞的杀伤活性。

Objective To investigate the roles of SENP1 in regulation of biological characteristics of NK cells. Methods Lentivirus-mediated-Senp1-small-hairpinRNA（ shRNA） transduction was applied to NK92 cells. The expression of SENP1 in NK92 cells was determined by real-time PCR and Western blot. The proliferation of NK92 cells was detected by CCK-8assay. The apoptosis of NK92 cells was determined by Annexin Ⅴ and PI labeling. The cytotoxicity of NK92 cells against K562 cells was evaluated by luciferase reporter assay. Results Treatment of NK92 cells with IL-21 resulted in SENP1 upregulation. Lentivirus mediated SENP1 knockdown reduced proliferation and increased apoptosis in NK-92 cells,but SENP1 inhibition had slight impact on the cytotoxic ability of NK92 cells to kill K562 cells. Conclusion SENP1 mediates the regulatory effect of IL-21 on the proliferation and survival of NK92 cells.