Title

Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

7-3-2009

Document Type

Article

Subjects

Animals; Antigen Presentation; Carrier Proteins; Cells, Cultured; Gene Expression Regulation; Humans; Inflammation; Macrophages; Mice; Mice, Knockout; Monocytes; NF-kappa B; Receptors, Cytokine; Receptors, Pattern Recognition; Signal Transduction; Transcriptional Activation

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences

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.

Rights and Permissions

Citation: J Immunol. 2009 Jul 15;183(2):787-91. Epub 2009 Jul 1. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

19570822