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LPS Activated Macrophages Induced Hepatocyte Pyroptosis via P2X7R Activation of NLRP3 in Mice | ||
| Iranian Journal of Immunology | ||
| دوره 19، شماره 1، خرداد 2022، صفحه 37-48 اصل مقاله (2.69 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22034/iji.2022.90579.2016 | ||
| نویسندگان | ||
| Lidan Luo؛ Yuan Fang؛ Qi Yuan؛ Jinmao Liao؛ Zheng Zhang* | ||
| Department of Hepatopathy, Hunan Provincial People’s Hospital (the first affiliated hospital of Hunan Normal University), Changsha, Hunan, China. | ||
| چکیده | ||
| Background: Pyroptosis is a programmed cell death related to caspase-1, accompanied by the secretion of pro-inflammatory cytokines. Objectives: To explore the effects of LPS on the P2X7R/NLRP3 pathway in macrophages, and hepatocytes pyroptosis in mice. Methods: LPS was used to establish an animal model of the acute liver injury. The macrophage RAW264.7 was induced by LPS to establish a cell model. The P2X7R inhibitor A438079 and agonist BZATP were added. RAW264.7 was co-cultured with AML-12 cells. Pyroptosis and the ratio of CD11b+CD86+/CD11b+CD206+ were analyzed by flow cytometry. ELISA, WB, and qRT-PCR were applied to analyze factors involved in the P2X7R/NLRP3 pathway. Results: LPS induced liver damage in mice, promoted cell pyroptosis and increased the levels of IL-18, IL-1β, ALT, AST, and TBIL. P2X7R, GSDMD, and GSDMD-N expressions also increased in the LPS group. LPS induced macrophage activation in vivo. NLRP3, ASC, P2X7R, and caspase-1 expressions in vitro promoted. ELISA confirmed that the IL-1β and IL-18 levels repressed in the BZATP (P2X7R agonist) group, while the trend was opposite in the A438079 (P2X7R inhibitor) group. LPS activated the P2X7R/NLRP3 pathway in macrophages. After RAW264.7 was co-cultured with AML-12 cells, the pyroptosis of AML-12 cells promoted but the proliferation decreased in the BZATP group. GSDMD and GSDMD-N expressions promoted in the BZATP group, while the trend was opposite in the A438079 group. Conclusion: LPS activated macrophages via P2X7R activation of NLRP3 and induced hepatocyte pyroptosis, which provided novel potential targets for the liver injury treatment. | ||
| کلیدواژه‌ها | ||
| Liver Injury؛ Macrophages؛ NLRP3؛ P2X7R؛ Pyroptosis | ||
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