The Signaling Pathways Regulating NLRP3 Inflammasome Activation

Inflammation. 2021 Aug;44(4):1229-1245. doi: 10.1007/s10753-021-01439-6. Epub 2021 May 19.


The NLRP3 inflammasome is a multi-molecular complex that acts as a molecular platform to mediate caspase-1 activation, leading to IL-1β/IL-18 maturation and release in cells stimulated by various pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). This inflammasome plays an important role in the innate immunity as its activation can further promote the occurrence of inflammation, enhance the ability of host to remove pathogens, and thus facilitate the repair of injured tissues. But if the inflammasome activation is dysregulated, it will cause the development of various inflammatory diseases and metabolic disorders. Therefore, under normal conditions, the activation of inflammasome is tightly regulated by various positive and negative signaling pathways to respond to the stimuli without damaging the host itself while maintaining homeostasis. In this review, we summarize recent advances in the major signaling pathways (including TLRs, MAPK, mTOR, autophagy, PKA, AMPK, and IFNR) that regulate NLRP3 inflammasome activation, providing a brief view of the molecular network that regulates this inflammasome as a theoretical basis for therapeutic intervention of NLRP3 dysregulation-related diseases.

Keywords: AMPK; Autophagy; MAPK; NLRP3 inflammasome; PKA; mTOR.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinase Kinases / metabolism
  • Animals
  • Humans
  • Inflammasomes / metabolism
  • Interleukin-1beta / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Signal Transduction / physiology*
  • TOR Serine-Threonine Kinases / metabolism


  • IL1B protein, human
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinase Kinases