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J Immunol. 2009 Jul 15;183(2):787-91. doi: 10.4049/jimmunol.0901363. Epub 2009 Jul 1.

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

Author information

1
Department of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

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.

PMID:
19570822
PMCID:
PMC2824855
DOI:
10.4049/jimmunol.0901363
[Indexed for MEDLINE]
Free PMC Article

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