Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/ hepatitis B-induced hepatic injury

Chen, Feng1,2; Liu, Yingxia2; Li, Qianhui1; Wang, Fei1

2023

10.1016/j.clinre.2022.102056

CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY   Impact Factor & Quartile

2210-7401

2210-741X

Background and aim: Both chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are the most common liver diseases over the world, but their underlying pathological mechanisms and interrelations are poorly understood. Methods: Histological analysis and NLRP3 protein expression were performed on 130 CHB patients with liver-biopsied. Wild-type or NLRP3 knockdown hepatitis B virus (HBV) -transgenic mice were fed with high-fat diet to induce steatosis, with or without co-administration with a novel NLRP3 inhibitor MCC950. Results: Hepatic NLRP3 inflammasome is markedly up-regulated in the CHB, NASH, superimposed NASH with CHB patients and their corresponding model mice. Hepatic knock-down of NLRP3 significantly inhibits HBV replication and surface antigen expression, as well as ameliorates NASH typical symptoms of HBV transgenic mice with or without high-fat diet consumption. In addition, administration of MCC950 successfully inhibits pathological features of both CHB and steatosis-induced liver damage without detectable adverse effects. Conclusions: NLRP3 inflammasome is activated during the progression of both CHB and NASH and may play a critical role in their pathogenesis by regulating hepatic inflammation. Targeting this protein platform may represent an effective and novel strategy for the treatment of CHB, NASH and the superimposed patients. (c) 2022 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

HBV Steatosis MCC950 NLRP3

SCI

English

Others

National Natural Science Foundation of China["81873573","81873578"]

Gastroenterology & Hepatology

Gastroenterology & Hepatology

WOS:000992203700001

ELSEVIER MASSON, CORP OFF

Web of Science

1.Sun Yat Sen Univ, Affiliated Hosp 7, Div Gastroenterol, 628 Zhenyuan Rd, Shenzhen 518107, Peoples R China
2.Southern Univ Sci & Technol, Natl Clin Res Ctr Infect Dis, Hosp Affiliated 2, Shenzhen 518112, Peoples R China

Chen, Feng,Liu, Yingxia,Li, Qianhui,et al. Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/ hepatitis B-induced hepatic injury[J]. CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY,2023,47(1).

Chen, Feng,Liu, Yingxia,Li, Qianhui,&Wang, Fei.(2023).Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/ hepatitis B-induced hepatic injury.CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY,47(1).

Chen, Feng,et al."Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/ hepatitis B-induced hepatic injury".CLINICS AND RESEARCH IN HEPATOLOGY AND GASTROENTEROLOGY 47.1(2023).