NLRP3 Inflammasome in Acute and Chronic Liver Diseases

Abstract

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is an intracellular complex that upon external stimuli or contact with specific ligands, recruits other components, forming the NLRP3 inflammasome. The NLRP3 inflammasome mainly mediates pyroptosis, a highly inflammatory mode of regulated cell death, as well as IL-18 and IL-1β production. Acute and chronic liver diseases are characterized by a massive influx of pro-inflammatory stimuli enriched in reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs) that promote the assemblage and activation of the NLRP3 inflammasome. As the major cause of inflammatory cytokine storm, the NLRP3 inflammasome exacerbates liver diseases, even though it might exert protective effects in regards to hepatitis C and B virus infection (HCV and HBV). Here, we summarize the current knowledge concerning NLRP3 inflammasome function in both acute and chronic liver disease and in the post liver transplant setting, focusing on the molecular mechanisms involved in NLRP3 activity.

Non-Alcoholic Fatty Liver Disease and the Risk of Future Hepatocarcinoma

“…An approach that targets the inflammasome, a crucial regulator of hepatic inflammation, could potentially mitigate hepatic fibrosis and inflammation in NAFLD. The investigation of inhibitors of the inflammasome, including caspase-1 inhibitors and NLRP3 inhibitors, is presently underway as a potential therapeutic approach for hepatocarcinoma associated with NAFLD (49).…”