Inflammasome activation and function in liver disease
Department of Medicine, Division of Gastroenterology
Medical Subject Headings
Acetaminophen; Animals; Disease Models, Animal; Disease Progression; Drug-Induced Liver Injury; Fatty Liver, Alcoholic; Hepatitis C, Chronic; Humans; Inflammasomes; Interleukin-18; Interleukin-1beta; Interleukin-33; Mice; Non-alcoholic Fatty Liver Disease; Reperfusion Injury
Digestive System Diseases | Gastroenterology | Hepatology | Immunopathology
Inflammation contributes to the pathogenesis of most acute and chronic liver diseases. Inflammasomes are multiprotein complexes that can sense danger signals from damaged cells and pathogens and assemble to mediate caspase-1 activation, which proteolytically activates the cytokines IL-1beta and IL-18. In contrast to other inflammatory responses, inflammasome activation uniquely requires two signals to induce inflammation, therefore setting an increased threshold. IL-1beta, generated upon caspase-1 activation, provides positive feed-forward stimulation for inflammatory cytokines, thereby amplifying inflammation. Inflammasome activation has been studied in different human and experimental liver diseases and has been identified as a major contributor to hepatocyte damage, immune cell activation and amplification of liver inflammation. In this Review, we discuss the different types of inflammasomes, their activation and biological functions in the context of liver injury and disease progression. Specifically, we focus on the triggers of inflammasome activation in alcoholic steatohepatitis and NASH, chronic HCV infection, ischaemia-reperfusion injury and paracetamol-induced liver injury. The application and translation of these discoveries into therapies promises novel approaches in the treatment of inflammation in liver disease.
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Citation: Nat Rev Gastroenterol Hepatol. 2015 Jul;12(7):387-400. doi: 10.1038/nrgastro.2015.94. Epub 2015 Jun 9. Link to article on publisher's site
Szabo, Gyongyi and Petrasek, Jan, "Inflammasome activation and function in liver disease" (2015). University of Massachusetts Medical School Faculty Publications. 974.