title: Inflammasome activation and function in liver disease.
abstract: 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-1β and IL-18. In contrast to other inflammatory responses, inflammasome activation uniquely requires two signals to induce inflammation, therefore setting an increased threshold. IL-1β, 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.
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, LRB 215, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Szabo
authors.affiliation: Department of Medicine, University of Massachusetts Medical School, LRB 215, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Petrasek
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000067596:Interleukin-33; D000082:Acetaminophen