NLRP3: a new therapeutic target in alcoholic liver disease

The liver is in charge of a wide range of critical physiological processes and it plays an important role in activating the innate immune system which elicits the inflammatory events. Chronic ethanol exposure disrupts hepatic inflammatory mechanism and leads to the release of proinflammatory mediators such as chemokines, cytokines and activation of inflammasomes. The mechanism of liver fibrosis/cirrhosis involve activation of NLRP3 inflammasome, leading to the destruction of hepatocytes and subsequent metabolic dysregulation in humans. In addition, increasing evidence suggests that alcohol intake significantly modifies liver epigenetics, promoting the development of alcoholic liver disease (ALD). Epigenetic changes including histone modification, microRNA-induced genetic modulation, and DNA methylation are crucial in alcohol-evoked cell signaling that affects gene expression in the hepatic system. Though we are at the beginning stage without having the entire print of epigenetic signature, it is time to focus more on NLRP3 inflammasome and epigenetic modifications. Here we review the novel aspect of ALD pathology linking to inflammation and highlighting the role of epigenetic modification associated with NLRP3 inflammasome and how it could be a therapeutic target in ALD.

Automated summary

The liver is responsible for important physiological processes and its role in activating the innate immune system and causing inflammation is crucial. Chronic ethanol exposure disrupts the liver's inflammatory mechanism and releases proinflammatory mediators. Activation of the NLRP3 inflammasome is involved in liver fibrosis/cirrhosis, leading to hepatocyte destruction and metabolic dysregulation. Alcohol intake also affects liver epigenetics, promoting the development of alcoholic liver disease (ALD). Understanding the role of NLRP3 inflammasome and epigenetic modifications could lead to potential therapeutic targets for ALD.