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 coculture...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Canadian Journal of Gastroenterology and Hepatology |
| Online Access: | http://dx.doi.org/10.1155/2022/6413783 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832549254144458752 |
|---|---|
| author | Mengnan Guo Wei Wang Wen Bai Zekun Bai Weixi Chen Yali Su Jinghua Wu |
| author_facet | Mengnan Guo Wei Wang Wen Bai Zekun Bai Weixi Chen Yali Su Jinghua Wu |
| author_sort | Mengnan Guo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b01e46f42f16421aae934fac1c027aa9 |
| institution | Kabale University |
| issn | 2291-2797 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Canadian Journal of Gastroenterology and Hepatology |
| spelling | doaj-art-b01e46f42f16421aae934fac1c027aa92025-02-03T06:11:53ZengWileyCanadian Journal of Gastroenterology and Hepatology2291-27972022-01-01202210.1155/2022/6413783Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling PathwayMengnan Guo0Wei Wang1Wen Bai2Zekun Bai3Weixi Chen4Yali Su5Jinghua Wu6Tangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalTangshan Maternal and Child Health Care HospitalAims. 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.http://dx.doi.org/10.1155/2022/6413783 |
| spellingShingle | Mengnan Guo Wei Wang Wen Bai Zekun Bai Weixi Chen Yali Su Jinghua Wu Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway Canadian Journal of Gastroenterology and Hepatology |
| title | Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway |
| title_full | Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway |
| title_fullStr | Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway |
| title_full_unstemmed | Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway |
| title_short | Depletion and Reversal of Hepatocellular Carcinoma Inducing CTL through ER Stress-Dependent PERK-CHOP Signaling Pathway |
| title_sort | depletion and reversal of hepatocellular carcinoma inducing ctl through er stress dependent perk chop signaling pathway |
| url | http://dx.doi.org/10.1155/2022/6413783 |
| work_keys_str_mv | AT mengnanguo depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT weiwang depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT wenbai depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT zekunbai depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT weixichen depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT yalisu depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway AT jinghuawu depletionandreversalofhepatocellularcarcinomainducingctlthrougherstressdependentperkchopsignalingpathway |