通过内质网应激依赖性PERK-CHOP信号通路诱导肝癌CTL的消耗和逆转。

IF 2.7 4区 医学 Q2 Medicine
Canadian Journal of Gastroenterology and Hepatology Pub Date : 2022-10-10 eCollection Date: 2022-01-01 DOI:10.1155/2022/6413783
Mengnan Guo, Wei Wang, Wen Bai, Zekun Bai, Weixi Chen, Yali Su, Jinghua Wu
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引用次数: 0

摘要

目的:研究肝癌细胞可引起细胞毒性T淋巴细胞(CTL)功能下调,茶多酚(TPs)可逆转CTL功能下调。方法:采用western blotting法检测CTLL-2与Hepa1-6共培养细胞中GRP78、PD-1、TIM-3的表达。采用酶联免疫吸附法(ELISA)和透射电镜(TEM)检测各组穿孔素(PRF1)和颗粒酶B (GzmB)蛋白水平和内质网形态。4-苯基丁酸(4-PBA)或tunicamycin (TM)处理后,采用western blotting和ELISA检测程序性细胞死亡蛋白1 (PD-1)、粘蛋白结构域3 (TIM-3)、PRF1和GzmB。sh-CHOP或GSK2656157 (PERK抑制剂)刺激后,在ctl -2细胞中检测到PERK- chop通路的激活。最后,通过检测PD-1、TIM-3、PRF1和GzmB水平的变化来验证TP对CTL消耗的逆转。结果:与肝癌细胞共培养的CTLL-2细胞中GRP78、PD-1、TIM-3的表达明显升高,内质网(ER)肿胀。同时,PRF1和GzmB水平降低。与4-PBA刺激不同,TM刺激可诱导ctl -2的消耗。sh-CHOP或GSK2656157处理导致PD-1和TIM-3表达降低,而PRF1和GzmB表达明显升高。添加TP后,ctl的功能明显增强。结论:肝癌细胞通过内质网应激PERK-CHOP通路诱导ctl的耗竭,TP通过下调内质网应激逆转这种耗竭。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway.

Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway.

Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway.

Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway.

Aims: In this report, it was investigated that hepatoma cells can cause downregulation of cytotoxic T lymphocyte (CTL) function and tea polyphenols (TPs) can reverse downregulation of CTL function.

Methods: The expression of GRP78, PD-1, and TIM-3 was detected by western blotting in CTLL-2 cocultured with Hepa1-6 cells. Moreover, perforin (PRF1) and granzyme B (GzmB) protein levels and ER morphology were examined by ELISA and TEM, respectively. After 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) treatment, programmed cell death protein 1 (PD-1), and mucin domain 3 (TIM-3), PRF1, and GzmB were measured by western blotting and ELISA. After sh-CHOP or GSK2656157 (PERK inhibitor) stimulation, the activation of the PERK-CHOP pathway was detected in CTLL-2 cells. Finally, changes in PD-1, TIM-3, PRF1, and GzmB levels were detected to verify the reversal of CTL depletion by TP.

Results: The expression of GRP78, PD-1, and TIM-3 clearly increased, and swelling was observed for the endoplasmic reticulum (ER) in CTLL-2 cells cocultured with hepatoma cells. Concurrently, the levels of PRF1 and GzmB decreased. CTLL-2 depletion was induced after stimulation with TM and differed from 4-PBA stimulation. Treatment with sh-CHOP or GSK2656157 caused a decrease in PD-1 and TIM-3 expression, whereas the expression of PRF1 and GzmB clearly increased. After adding TP, the function of CTLs increased markedly.

Conclusion: Hepatoma cells induced the depletion of CTLs through the ER stress PERK-CHOP pathway, and TP reversed this depletion by downregulating ER stress.

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来源期刊
CiteScore
4.80
自引率
0.00%
发文量
0
审稿时长
37 weeks
期刊介绍: Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery. The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.
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