Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration

V. Pétrilli, S. Papin, C. Dostert, A. Mayor, F. Martinon, J. Tschopp*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

1060 Citations (Scopus)

Abstract

Inflammasomes are Nod-like receptor(NLR)- and caspase-1-containing cytoplasmic multiprotein complexes, which upon their assembly, process and activate the proinflammatory cytokines interleukin (IL)-1β and IL-18. The inflammasomes harboring the NLR members NALP1, NALP3 and IPAF have been best characterized. While the IPAF inflammasome is activated by bacterial flagellin, activation of the NALP3 inflammasome is triggered not only by several microbial components, but also by a plethora of danger-associated host molecules such as uric acid. How NALP3 senses these chemically unrelated activators is not known. Here, we provide evidence that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K+ efflux from cells. Low intracellular K+ is also a requirement for NALP1 inflammasome activation by lethal toxin of Bacillus anthracis. In vitro, NALP inflammasome assembly and caspase-1 recruitment occurs spontaneously at K+ concentrations below 90 mM, but is prevented at higher concentrations. Thus, low intracellular K+ may be the least common trigger of NALP-inflammasome activation.

Original languageEnglish
Pages (from-to)1583-1589
Number of pages7
JournalCell Death and Differentiation
Volume14
Issue number9
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

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