Hepatitis B virus-mediated sodium influx contributes to hepatic inflammation via synergism with intrahepatic danger signals

作者全名："Wang, Jingxue; Liu, Qian; Zhou, Yiwen; Cao, Chunhao; Chen, Penghui; Meng, Gang; Zhang, Ji; Xin, Xiaojuan; Huang, Guangyu; Wu, Yuzhang"

作者地址："[Wang, Jingxue; Zhou, Yiwen; Zhang, Ji; Wu, Yuzhang] Army Med Univ, Dept Immunol, Chongqing, Peoples R China; [Liu, Qian] Army Med Univ, Southwest Hosp, Dept Clin Lab Med, Chongqing, Peoples R China; [Cao, Chunhao] Chongqing Med Univ, Affiliate Hosp 1, Dept Integrated Tradit Chinese & Western Med, Chongqing, Peoples R China; [Chen, Penghui] Army Med Univ, Dept Neurobiol, Chongqing, Peoples R China; [Huang, Guangyu] Army Med Univ, Southwest Hosp, Dept Pathol, Chongqing, Peoples R China; [Xin, Xiaojuan] Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China; [Huang, Guangyu] Zhejiang Univ, Affiliated Hosp 4, Sch Med, Dept Infect Dis, Yiwu, Zhejiang, Peoples R China"

通信作者："Wang, JX; Wu, YZ (通讯作者)，Army Med Univ, Dept Immunol, Chongqing, Peoples R China.; Huang, GY (通讯作者)，Army Med Univ, Southwest Hosp, Dept Pathol, Chongqing, Peoples R China.; Xin, XJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Infect Dis, Chongqing, Peoples R China.; Huang, GY (通讯作者)，Zhejiang Univ, Affiliated Hosp 4, Sch Med, Dept Infect Dis, Yiwu, Zhejiang, Peoples R China."

来源：ISCIENCE

ESI学科分类：　

WOS号：WOS:001155273300001

JCR分区：Q1

影响因子：5.8

年份：2024

卷号：27

期号：1

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome has been involved in the pathogenesis of various chronic liver diseases. However, its role in hepatitis B virus (HBV)-associated hepatitis remains unknown. Here we demonstrate the synergistic effect of HBV with potential intrahepatic danger signals on NLRP3 inflammasome activation. HBV exposure at the appropriate temporal points enhances potassium efflux-dependent NLRP3 inflammasome activation in macrophages and also increases NLRP3 inflammasome-mediated inflammation in HBV-transgenic mouse model. HBV-mediated synergism with intrahepatic signals represented by ATP molecules on NLRP3 activation was observed via relevance analysis, confocal microscopy, and co-immunoprecipitation, and its effector cytokines exhibit positive associations with hepatic inflammation in patients with severe hepatitis B. Furthermore, the synergism of HBV on NLRP3 inflammasome activation owes to increased sodium influx into macrophages. Our data demonstrate that HBV contributes to hepatic inflammation via sodium influx-dependent synergistic activation of NLRP3 inflammasome, which provides a deeper understanding of immune pathogenesis in HBVassociated hepatitis."

基金机构："National Key R&D Program of China [2016YFA0502200]; National Natural Science Foundation of China [31670899, 32270987]; Natural Science Foundation of Chongqing [2021jcyj-msxmX0657]; Medical Scientific Research major project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) [2019ZDXM004]"

基金资助正文："This work was funded by the National Key R&D Program of China (2016YFA0502200) , the National Natural Science Foundation of China (Grant No. 31670899 and 32270987) and the Natural Science Foundation of Chongqing (Grant No. CSTC, 2021jcyj-msxmX0657) , and Medical Scientific Research major project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (Grant No. 2019ZDXM004) ."