Role of the Inflammasome in Liver Disease

Annu Rev Pathol. 2022 Jan 24:17:345-365. doi: 10.1146/annurev-pathmechdis-032521-102529. Epub 2021 Nov 9.

Abstract

The involvement of inflammasomes in the proinflammatory response observed in chronic liver diseases, such as alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), is widely recognized. Although there are different types of inflammasomes, most studies to date have given attention to NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) in the pathogenesis of ALD, NAFLD/nonalcoholic steatohepatitis, and fibrosis. Canonical inflammasomes are intracellular multiprotein complexes that are assembled after the sensing of danger signals and activate caspase-1, which matures interleukin (IL)-1β, IL-18, and IL-37 and also induces a form of cell death called pyroptosis. Noncanonical inflammasomes activate caspase-11 to induce pyroptosis. We discuss the different types of inflammasomes involved in liver diseases with a focus on (a) signals and mechanisms of inflammasome activation, (b) the role of different types of inflammasomes and their products in the pathogenesis of liver diseases, and (c) potential therapeutic strategies targeting components of the inflammasomes or cytokines produced upon inflammasome activation.

Keywords: GSDMD; IL-18; IL-1β; alcohol-associated liver diseases; canonical inflammasomes; hepatocyte; macrophage; nonalcoholic steatohepatitis; noncanonical inflammasomes; pyroptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Inflammasomes* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Non-alcoholic Fatty Liver Disease*
  • Pyroptosis

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein