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Distinct licensing of IL-18 and IL-1? secretion in response to NLRP3 inflammasome activation.

ABSTRACT: Inflammasome activation permits processing of interleukins (IL)-1? and 18 and elicits cell death (pyroptosis). Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1) activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm) p60 protein. Primed murine dendritic cells (DCs) responded to p60 stimulation with reactive oxygen species (ROS) production and secretion of IL-1? and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1?, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11)-deficient 129S6 mice failed to secrete IL-1? in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1? by NLRP3 inflammasomes.

SUBMITTER: Schmidt RL

PROVIDER: S-EPMC3445464 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

Schmidt Rebecca L RL Lenz Laurel L LL

PloS one 20120918 9

Inflammasome activation permits processing of interleukins (IL)-1β and 18 and elicits cell death (pyroptosis). Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1) activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm) p60 protein. Primed murine dendritic cells (DCs) responded to p6 ...[more]

PMID: 23028835

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