Mechanism and Regulation of NLRP3 Inflammasome Activation

Trends Biochem Sci. 2016 Dec;41(12):1012-1021. doi: 10.1016/j.tibs.2016.09.002. Epub 2016 Sep 23.

Abstract

Members of the nucleotide-binding domain and leucine-rich repeat (LRR)-containing (NLR) family and the pyrin and HIN domain (PYHIN) family can form multiprotein complexes termed 'inflammasomes'. The biochemical function of inflammasomes is to activate caspase-1, which leads to the maturation of interleukin 1 beta (IL-1β) and IL-18 and the induction of pyroptosis, a form of cell death. Unlike other inflammasomes, the NLRP3 inflammasome can be activated by diverse stimuli. The importance of the NLRP3 inflammasome in immunity and human diseases has been well documented, but the mechanism and regulation of its activation remain unclear. In this review we summarize current understanding of the mechanism and regulation of NLRP3 inflammasome activation as well as recent advances in the noncanonical and alternative inflammasome pathways.

Keywords: K(+) efflux; NLRP3 inflammasome; Nek7; alternative inflammasome; noncanonical inflammasome.

Publication types

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

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / immunology*
  • Gene Expression Regulation / immunology
  • Humans
  • Inflammasomes / agonists
  • Inflammasomes / genetics
  • Inflammasomes / immunology*
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Ion Transport
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology
  • NIMA-Related Kinases / genetics
  • NIMA-Related Kinases / immunology
  • NLR Family, Pyrin Domain-Containing 3 Protein / agonists
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / immunology*
  • Potassium / immunology
  • Potassium / metabolism
  • Pyroptosis / genetics
  • Pyroptosis / immunology*
  • Signal Transduction

Substances

  • IL1B protein, human
  • Inflammasomes
  • Interleukin-18
  • Interleukin-1beta
  • Lipopolysaccharides
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • interleukin 18 protein, human
  • NEK7 protein, human
  • NIMA-Related Kinases
  • Caspase 1
  • Potassium