文献类型：期刊文献

英文题名：IL-17 Imbalance Promotes the Pyroptosis in Immune-Mediated Liver Injury Through STAT3-IFI16 Axis

作者：Xu, Wenfang[1,5];Wang, Yanan[1];Jin, Changzhong[2];Zhang, Weiyang[1];Chen, Jiangnan[1];Chen, Xuefang[1];Gao, Junli[3,4];Gao, Junshun[3,4];Wang, Hong[3,4,6]

机构：[1]Shaoxing Univ, Dept Clin Lab, Affiliated Hosp, Shaoxing 312020, Peoples R China;[2]Zhejiang Univ, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310027, Peoples R China;[3]Zhejiang Univ, Med Sch, Hangzhou Cosmos Wisdom Mass Spectrometry Ctr, Hangzhou 311200, Peoples R China;[4]Key Lab Precis Med Diag & Monitoring Res Zhejiang, Hangzhou 310016, Peoples R China;[5]Shaoxing Univ, Affiliated Hosp, Dept Clin Lab, 999 Zhongxing South Rd, Shaoxing 312000, Peoples R China;[6]Zhejiang Univ, Med Sch, Hangzhou Cosmos Wisdom Mass Spectrometry Ctr, 198 Qidi Rd, Hangzhou 311200, Peoples R China

年份：2023

卷号：23

期号：6

外文期刊名：IMMUNE NETWORK

收录：SCI-EXPANDED(收录号：WOS:001134911400002)、、Scopus(收录号：2-s2.0-85182838930)、WOS

基金：This work was supported by grant from the Zhejiang Basic Public Welfare Research Project (LGF20H100001) , founded by Zhejiang Provincial Department of Science and Technology.

语种：英文

外文关键词：Autoimmune hepatitis; IL-17; Pyroptosis; IL-17-STAT3-IFI16 axis; Liver injury

外文摘要：Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gammainducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.