Biochemical regulation of the inflammasome

Crit Rev Biochem Mol Biol. 2012 Sep;47(5):424-43. doi: 10.3109/10409238.2012.694844. Epub 2012 Jun 11.

Abstract

The extensively studied cytokine IL-1β is an important mediator of the inflammatory response. However, dysregulated release of IL-1β can be detrimental and is attributed to the progression and pathogenesis of multiple inflammatory diseases including, rhuematoid arthritis (RA), atherosclerosis, type 2 diabetes (T2D), Alzheimers disease and gout. IL-1β is encoded as a pro-protein. A multi-protein molecular scaffold termed the "Inflammasome" is responsible for the tightly controlled and coordinated processing of pro-IL-1β. The activation of several NLR (nucleotide-binding oligomerization domain (NOD)-like receptor) family members and PYHIN (pyrin and HIN domain) proteins can drive the formation of inflammasomes. However, the exact biochemical mechanisms governing their activation have been the subject of much research. Different inflammasomes have been demonstrated to respond to the same pathogen inducing a cooperative immune response accountable for the clearance of infection. Here, we review current knowledge surrounding the biochemical regulation of the NLRP1, NLRP3, NLRC4, AIM2 and IFI16 inflammasomes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Bacteria / immunology
  • Bacteria / pathogenicity
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Caspase 1 / metabolism*
  • Cytosol / immunology
  • Cytosol / metabolism
  • Cytosol / microbiology
  • Enzyme Activation
  • Gene Expression Regulation*
  • Humans
  • Inflammasomes / genetics
  • Inflammasomes / immunology
  • Inflammasomes / metabolism*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism*
  • Lysosomes / metabolism
  • Mice
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Potassium / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • Inflammasomes
  • Inflammation Mediators
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP1 protein, human
  • Nlrp3 protein, mouse
  • Reactive Oxygen Species
  • Caspase 1
  • Potassium