GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection
Tuberculosis (TB) is the leading cause of human death worldwide due to <i>Mycobacterium tuberculosis</i> (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It i...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16239 |
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| author | Boli Ma Xueyi Nie Lei Liu Mengyuan Li Qi Chen Yueyang Liu Yuxin Hou Yi Yang Jinrui Xu |
| author_facet | Boli Ma Xueyi Nie Lei Liu Mengyuan Li Qi Chen Yueyang Liu Yuxin Hou Yi Yang Jinrui Xu |
| author_sort | Boli Ma |
| collection | DOAJ |
| description | Tuberculosis (TB) is the leading cause of human death worldwide due to <i>Mycobacterium tuberculosis</i> (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It is not clear whether PERK is involved in the regulation of pyroptosis of macrophages during Mtb infection. In this study, <i>Bacillus Calmette–Guerin</i> (BCG) infection resulted in high expression of pro-caspase-1, caspase-1 p20, GSDMD-N, and p-PERK in the THP-1 macrophage, being downregulated with the pre-treatment of GSK2656157, a PERK inhibitor. In addition, GSK2656157 inhibited the secretion of IL-1β and IL-18, cell content release, and cell membrane rupture, as well as the decline in cell viability induced by BCG infection. Similarly, GSK2656157 treatment downregulated the expressions of pro-caspase-1, caspase-1 p20, caspase-11, IL-1β p17, IL-18 p22, GSDMD, GSDMD-N, and p-PERK, as well as reducing fibrous tissue hyperplasia, inflammatory infiltration, and the bacterial load in the lung tissue of C57BL/6J mice infected with BCG. In conclusion, the inhibition of PERK alleviated pyroptosis induced by BCG infection, which has an effect of resisting infection. |
| first_indexed | 2024-03-09T16:45:57Z |
| format | Article |
| id | doaj.art-708e6e32530241d6b2a6232ad0a826b2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:57Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-708e6e32530241d6b2a6232ad0a826b22023-11-24T14:46:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221623910.3390/ijms242216239GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> InfectionBoli Ma0Xueyi Nie1Lei Liu2Mengyuan Li3Qi Chen4Yueyang Liu5Yuxin Hou6Yi Yang7Jinrui Xu8School of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaSchool of Life Sciences, Ningxia University, Yinchuan 750021, ChinaTuberculosis (TB) is the leading cause of human death worldwide due to <i>Mycobacterium tuberculosis</i> (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It is not clear whether PERK is involved in the regulation of pyroptosis of macrophages during Mtb infection. In this study, <i>Bacillus Calmette–Guerin</i> (BCG) infection resulted in high expression of pro-caspase-1, caspase-1 p20, GSDMD-N, and p-PERK in the THP-1 macrophage, being downregulated with the pre-treatment of GSK2656157, a PERK inhibitor. In addition, GSK2656157 inhibited the secretion of IL-1β and IL-18, cell content release, and cell membrane rupture, as well as the decline in cell viability induced by BCG infection. Similarly, GSK2656157 treatment downregulated the expressions of pro-caspase-1, caspase-1 p20, caspase-11, IL-1β p17, IL-18 p22, GSDMD, GSDMD-N, and p-PERK, as well as reducing fibrous tissue hyperplasia, inflammatory infiltration, and the bacterial load in the lung tissue of C57BL/6J mice infected with BCG. In conclusion, the inhibition of PERK alleviated pyroptosis induced by BCG infection, which has an effect of resisting infection.https://www.mdpi.com/1422-0067/24/22/16239PERK<i>Bacillus Calmette–Guerin</i>macrophagespyroptosis |
| spellingShingle | Boli Ma Xueyi Nie Lei Liu Mengyuan Li Qi Chen Yueyang Liu Yuxin Hou Yi Yang Jinrui Xu GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection International Journal of Molecular Sciences PERK <i>Bacillus Calmette–Guerin</i> macrophages pyroptosis |
| title | GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection |
| title_full | GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection |
| title_fullStr | GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection |
| title_full_unstemmed | GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection |
| title_short | GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium <i>Bacillus Calmette–Guerin</i> Infection |
| title_sort | gsk2656157 a perk inhibitor alleviates pyroptosis of macrophages induced by mycobacterium i bacillus calmette guerin i infection |
| topic | PERK <i>Bacillus Calmette–Guerin</i> macrophages pyroptosis |
| url | https://www.mdpi.com/1422-0067/24/22/16239 |
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