Key Points
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Inflammasomes are multiprotein complexes that assemble upon the sensing of danger signals and initiate the release of proinflammatory cytokines IL-1β and IL-18 via caspase-1 activation
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By responding to low-threshold signals, the inflammasome is able to fine-tune the inflammatory response
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The balance between a healthy inflammatory response and chronic damage is delicate and several inflammasomes, such as NLRP3, NLRP6 and AIM2, also have a role in liver diseases
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Among other diseases, inflammasome activation contributes to alcoholic steatohepatitis and NASH, chronic HCV infection, ischaemia–reperfusion injury, paracetamol-induced liver injury and liver fibrosis
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.
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Szabo, G., Petrasek, J. Inflammasome activation and function in liver disease. Nat Rev Gastroenterol Hepatol 12, 387–400 (2015). https://doi.org/10.1038/nrgastro.2015.94
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DOI: https://doi.org/10.1038/nrgastro.2015.94
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