The NLRP3 inflammasome: activation and regulation

Trends Biochem Sci. 2023 Apr;48(4):331-344. doi: 10.1016/j.tibs.2022.10.002. Epub 2022 Nov 4.

Abstract

The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is a cytoplasmic supramolecular complex that is activated in response to cellular perturbations triggered by infection and sterile injury. Assembly of the NLRP3 inflammasome leads to activation of caspase-1, which induces the maturation and release of interleukin-1β (IL-1β) and IL-18, as well as cleavage of gasdermin D (GSDMD), which promotes a lytic form of cell death. Production of IL-1β via NLRP3 can contribute to the pathogenesis of inflammatory disease, whereas aberrant IL-1β secretion through inherited NLRP3 mutations causes autoinflammatory disorders. In this review, we discuss recent developments in the structure of the NLRP3 inflammasome, and the cellular processes and signaling events controlling its assembly and activation.

Keywords: Golgi; metabolism; mitochondria; phosphorylation; potassium efflux; ubiquitination.

Publication types

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

MeSH terms

  • Caspase 1 / metabolism
  • Gene Expression
  • Inflammasomes* / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Signal Transduction

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Caspase 1
  • Interleukin-1beta