%0 Journal Article %T LPS Activated Macrophages Induced Hepatocyte Pyroptosis via P2X7R Activation of NLRP3 in Mice %J Iranian Journal of Immunology %I Shiraz Institute for Cancer Research %Z 1735-1383 %A Luo, Lidan %A Fang, Yuan %A Yuan, Qi %A Liao, Jinmao %A Zhang, Zheng %D 2022 %\ 03/01/2022 %V 19 %N 1 %P 37-48 %! LPS Activated Macrophages Induced Hepatocyte Pyroptosis via P2X7R Activation of NLRP3 in Mice %K Liver injury %K macrophages %K NLRP3 %K P2X7R %K Pyroptosis %R 10.22034/iji.2022.90579.2016 %X 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. %U https://iji.sums.ac.ir/article_48262_80944aebe84285e2508d0b52e89acbc1.pdf