Inhibition of hepatic NLRP3 inflammasome ameliorates non-alcoholic steatohepatitis/hepatitis B - induced hepatic injury - 07/01/23
Highlights |
• | The prevalence of NAFLD/NASH in CHB patients is relatively high in affluent Chinese region. |
• | NLRP3 is frequently up-regulated in CHB, NASH, superimposed NASH with CHB patients. |
• | Consumption of high-fat diet, rather than HBV, is the main determinant of hepatic steatosis development. |
• | Superimposed NASH might be helpful in inhibiting HBV replication and clearing serum HBeAg. |
• | Inhibition of hepatic NLRP3 inflammasome ameliorates HBV/steatosis-induced hepatic injury in vivo. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Keywords : HBV, Steatosis, NLRP3, MCC950
Abbreviations : CHB, NAFLD, NASH, HBV, WHO, HBsAg, HCC, PAMPs, DAMPs, NLRP3, ATP, ROS, IL-1β, IL-18, AAV, ALT, AST, ALP, ALB, TC, TG, HDL, LDL, TNF, NAS, ITT, GTT, SD, NF-κB
Plan
Vol 47 - N° 1
Article 102056- janvier 2023 Retour au numéro
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