title: Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome.
abstract: A common denominator among the multiple damage-inducing agents that ultimately lead to activation of NLRP3 has not yet been identified. Recently, production of reactive oxygen species (ROS) has been suggested to act as a common event upstream of the NLRP3 inflammasome machinery. Because de novo translation of NLRP3 is an essential step in the activation of NLRP3, we investigated the role of substances that inhibit either ROS production or its oxidative activity. Although we observe that NLRP3 inflammasome activation is unique among other known inflammasomes in its sensitivity to ROS inhibition, we have found that this phenomenon is attributable to the fact that NLRP3 strictly requires priming by a proinflammatory signal, a step that is blocked by ROS inhibitors. Although these data do not exclude a general role for ROS production in the process of NLRP3-triggered inflammation, they would put ROS upstream of NLRP3 induction, but not activation.
authors.affiliation: Unit for Clinical Biochemistry, Institute for Clinical Chemistry and Pharmacology, University Hospital, University of Bonn, 53127 Bonn, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Bauernfeind
authors.forename: Eva
authors.initials: E
authors.lastname: Bartok
authors.forename: Anna
authors.initials: A
authors.lastname: Rieger
authors.forename: Luigi
authors.initials: L
authors.lastname: Franchi
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
authors.forename: Veit
authors.initials: V
authors.lastname: Hornung
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology*; D058847:Inflammasomes / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology
chemical_list: D001713:Biphenyl Compounds; D002352:Carrier Proteins; D058847:Inflammasomes; D008562:Membrane Glycoproteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; C031291:diphenyliodonium; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1