干扰素-γ通过PI3K/Akt/mTOR通路上调程序性死亡受体-配体1促进非霍奇金淋巴瘤细胞增殖

doi:10.6040/j.issn.1671-7554.0.2022.1081

摘要/Abstract

摘要： 目的探讨干扰素-γ(IFN-γ)调控程序性死亡受体-配体1(PD-L1)的表达对非霍奇金淋巴瘤(NHL)增殖的影响及其机制。方法应用流式细胞术检测多种NHL细胞株中PD-L1的表达;利用IFN-γ处理NHL细胞株U937及Jeko-1后,通过流式细胞术及实时定量PCR(qRT-PCR)法检测PD-L1的表达水平;通过INF-γ及磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路抑制剂共培养NHL细胞后,应用蛋白免疫印迹法及流式细胞术法检测NHL细胞PD-L1的表达水平;通过细胞毒性检测试剂盒(CCK-8)和羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)染色掺入检测细胞增殖,应用Edu标记法检测细胞增殖率,并用流式细胞术检测细胞周期。结果 qRT-PCR法显示,多种NHL细胞株表面均表达PD-L1; IFN-γ处理后,U937及Jeko-1细胞PD-L1的mRNA及蛋白表达水平均升高; IFN-γ及信号通路抑制剂处理U937和Jeko-1细胞后, PI3K/Akt/mTOR信号通路抑制剂抑制IFN-γ上调PD-L1的表达。IFN-γ及信号通路抑制剂共处理U937及Jeko-1细胞后,IFN-γ促进的细胞增殖被抑制。结论 IFN-γ可以通过PI3K/Akt/mTOR信号通路上调NHL细胞PD-L1的表达;IFN-γ通过上调NHL细胞PD-L1的表达促进NHL细胞增殖。

关键词: 非霍奇金淋巴瘤, 程序性死亡受体-配体1, 干扰素-γ, 磷脂酰肌醇-3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白

Abstract: Objective To explore the effects of interferon-γ(IFN-γ)on the proliferation of non-Hodgkin lymphoma(NHL)by regulating the expression of programmed cell death ligand 1(PD-L1)and the mechanism. Methods The expression of PD-L1 in various NHL cell lines was detected with flow cytometry. After NHL cell lines U937 and Jeko-1 were treated with IFN-γ, the expression of PD-L1 was detected with flow cytometry and quantitative real-time PCR(qRT-PCR). After NHL cells were co-cultured with INF-γ and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway inhibitor, change in the expression of PD-L1 was detected with Western blotting and flow cytometry. Cell proliferation was detected with cytotoxicity detection kit(CCK-8)and carboxyfluorescein diacetate succinimidyl ester(CFSE)staining incorporation method. Cell proliferation rate was detected with Edu labeling method. Cell cycle was detected with flow cytometry. Results The qRT-PCR results showed that PD-L1 was expressed on the surface of various NHL cell lines. After IFN-γ treatment, the mRNA and protein expressions of PD-L1 in U937 and Jeko-1 cells were increased. After U937 and Jeko-1 cells were co-treated with IFN-γ and signaling pathway inhibitors, the PI3K/Akt/mTOR signaling pathway inhibitor inhibited the up-regulation of PD-L1 expression by IFN-γ, and cell proliferation was inhibited. Conclusion IFN-γ can up-regulate the expression of PD-L1 in NHL cells through the PI3K/Akt/mTOR signaling pathway; IFN-γ promotes NHL cell proliferation by up-regulating the expression of PD-L1.

Key words: Non-Hodgkin lymphoma, Programmed cell death ligand 1, Interferon-γ, Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

中图分类号:

R574

谢晓丽, 邱雨, 王丽娟. 干扰素-γ通过PI3K/Akt/mTOR通路上调程序性死亡受体-配体1促进非霍奇金淋巴瘤细胞增殖[J]. 山东大学学报 (医学版), 2023, 61(5): 11-19.

XIE Xiaoli, QIU Yu, WANG Lijuan. IFN-γ promots the proliferation of NHL by up-regulating PD-L1 via PI3K/Akt/mTOR pathway[J]. Journal of Shandong University (Health Sciences), 2023, 61(5): 11-19.

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