Effect and mechanism of reactive oxygen species-mediated NOD-like receptor family pyrin domain-containing 3 inflammasome activation in hepatic alveolar echinococcosis  

作　　者：Cai-Song Chen Yao-Gang Zhang Hai-Jiu Wang Hai-Ning Fan 

机构地区：[1]Research Center for High Altitude Medicine of Qinghai University,Affiliated Hospital of Qinghai University,Xining 810001,Qinghai Province,China [2]Qinghai Province Research Key Laboratory for Echinococcosis,Affiliated Hospital of Qinghai University,Xining 810001,Qinghai Province,China [3]Department of Hepatobiliary and Pancreatic Surgery,Qinghai Province Research Key Laboratory for Echinococcosis,Affiliated Hospital of Qinghai University,Xining 810001,Qinghai Province,China

出　　处：《World Journal of Gastroenterology》2023年第14期2153-2171,共19页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Major Research and Development Project of“Precision Medicine Research”,No.2017YFC0909900;Qinghai Province Science and Technology Department Programme,No.2019-SF-131;the Qinghai Province Health and Family Planning Commission Programme,No.2016-wjzd-04.

摘　　要：BACKGROUND The NOD-like receptor family pyrin domain-containing 3(NLRP3)inflammasome is a significant component of the innate immune system that plays a vital role in the development of various parasitic diseases.However,its role in hepatic alveolar echinococcosis(HAE)remains unclear.AIM To investigate the NLRP3 inflammasome and its mechanism of activation in HAE.METHODS We assessed the expression of NLRP3,caspase-1,interleukin(IL)-1β,and IL-18 in the marginal zone and corresponding normal liver of 60 patients with HAE.A rat model of HAE was employed to investigate the role of the NLRP3 inflammasome in the marginal zone of HAE.Transwell experiments were conducted to investigate the effect of Echinococcus multilocularis(E.multilocularis)in stimulating Kupffer cells and hepatocytes.Furthermore,immunohistochemistry,Western blotting,and enzyme-linked immunosorbent assay were used to evaluate NLRP3,caspase-1,IL-1β,and IL-18 expression;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS).RESULTS NLRP3 inflammasome activation was significantly associated with ROS.Inhibition of ROS production decreased NLRP3-caspase-1-IL-1βpathway activation and mitigated hepatocyte damage and inflammation.CONCLUSION E.multilocularis induces hepatocyte damage and inflammation by activating the ROS-mediated NLRP3-caspase-1-IL-1βpathway in Kupffer cells,indicating that ROS may serve as a potential target for the treatment of HAE.

关 键 词：Hepatic alveolar echinococcosis INFLAMMASOME Inflammation Kupffer cell NLR family pyrin domain-containing 3 protein Reactive oxygen species 

分 类 号：R532.32[医药卫生—内科学]