Human NLRP3 inflammasome activation is Nox1-4 independent.
The NLRP3 inflammasome can be activated by pathogen-associated molecular patterns or endogenous danger-associated molecular patterns. The activation of the NLRP3 inflammasome results in proteolytic activation and secretion of cytokines of the interleukin-1 (IL-1) family. The precise mode of activation of the NLRP3 inflammasome is still elusive, but has been postulated to be mediated by reactive oxygen species (ROS) generated by an NADPH oxidase. Using primary cells from chronic granulomatous disease (CGD) patients lacking expression of p22(phox), a protein that is required for the function of Nox1-4, we show that cells lacking NADPH oxidase activity are capable of secreting normal amounts of IL-1beta. Thus, we provide evidence that activation of the NLRP3 inflammasome does not depend on ROS generated from an NADPH oxidase.
van Bruggen
Robin
R
Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, Amsterdam, The Netherlands. r.vanbruggen@sanquin.nl
Köker
M Yavuz
MY
Jansen
Machiel
M
van Houdt
Michel
M
Roos
Dirk
D
Kuijpers
Taco W
TW
van den Berg
Timo K
TK
D002352:Carrier Proteins / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000276:immunology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017382:Reactive Oxygen Species / Q000276:immunology
D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D000074624:NADPH Oxidase 1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C498910:NOX4 protein, human