title: Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression.
abstract: The IL-1 family cytokines are regulated on transcriptional and posttranscriptional levels. Pattern recognition and cytokine receptors control pro-IL-1beta transcription whereas inflammasomes regulate the proteolytic processing of pro-IL-1beta. The NLRP3 inflammasome, however, assembles in response to extracellular ATP, pore-forming toxins, or crystals only in the presence of proinflammatory stimuli. How the activation of gene transcription by signaling receptors enables NLRP3 activation remains elusive and controversial. In this study, we show that cell priming through multiple signaling receptors induces NLRP3 expression, which we identified to be a critical checkpoint for NLRP3 activation. Signals provided by NF-kappaB activators are necessary but not sufficient for NLRP3 activation, and a second stimulus such as ATP or crystal-induced damage is required for NLRP3 activation.
authors: Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors: Franz G
authors: FG
authors: Bauernfeind
authors: Gabor
authors: G
authors: Horvath
authors: Andrea
authors: A
authors: Stutz
authors: Emad S
authors: ES
authors: Alnemri
authors: Kelly
authors: K
authors: MacDonald
authors: David
authors: D
authors: Speert
authors: Teresa
authors: T
authors: Fernandes-Alnemri
authors: Jianghong
authors: J
authors: Wu
authors: Brian G
authors: BG
authors: Monks
authors: Katherine A
authors: KA
authors: Fitzgerald
authors: Veit
authors: V
authors: Hornung
authors: Eicke
authors: E
authors: Latz
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D016328:NF-kappa B / Q000502:physiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018121:Receptors, Cytokine / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D002352:Carrier Proteins; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D018121:Receptors, Cytokine; D051192:Receptors, Pattern Recognition