Molecular mechanism of NLRP3 inflammasome activation.
The inflammasome is an intracellular multimolecular complex that controls caspase-1 activity in the innate immune system. NLRP3, a member of the NLR family of cytosolic pattern recognition receptors, along with the adaptor protein ASC, mediates caspase-1 activation via assembly of the inflammasome in response to various pathogen-derived factors as well as danger-associated molecules. The active NLRP3 inflammasome drives innate immune response towards invading pathogens and cellular damage, and regulates adaptive immune response. Here, we review identified agonists of the NLRP3 inflammasome and the molecular mechanism by which they induce NLRP3 inflammasome activation. Three signaling pathways involving potassium efflux, generation of reactive oxygen species, and cathepsin B release are discussed.
Jin
Chengcheng
C
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, TAC S-560, New Haven, CT 06520, USA.
Flavell
Richard A
RA
D000818:Animals; D002352:Carrier Proteins / Q000819:agonists / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D006801:Humans; D007239:Infections / Q000276:immunology*; D058847:Inflammasomes / Q000276:immunology*; D053583:Interleukin-1beta / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018384:Oxidative Stress / Q000276:immunology; D011188:Potassium / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051192:Receptors, Pattern Recognition / Q000819:agonists / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013312:Stress, Physiological / Q000276:immunology
D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D051192:Receptors, Pattern Recognition; D002401:Cathepsin B; D020170:Caspase 1; D011188:Potassium