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Sphingosine regulates the NLRP3-inflammasome and IL-1? release from macrophages.

ABSTRACT: Interleukin-1? (IL-1?) is a pro-inflammatory cytokine that regulates inflammatory responses to injury and infection. IL-1? secretion requires the protease caspase-1, which is activated following recruitment to inflammasomes. Endogenous danger-associated molecular patterns (DAMPs) released from necrotic cells activate caspase-1 through an NLRP3-inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1? from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited Sph-induced IL-1? release. IL-1? release induced by other well-characterized NLRP3-inflammasome activators, such as ATP and uric acid crystals, in addition to NLRC4 and AIM2 inflammasome activators was also blocked by these inhibitors. Thus, we propose Sph as a new DAMP, and that a serine/threonine phosphatase (PP1/PP2A)-dependent signal is central to the endogenous host mechanism through which diverse stimuli regulate inflammasome activation.

SUBMITTER: Luheshi NM

PROVIDER: S-EPMC3491674 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Sphingosine regulates the NLRP3-inflammasome and IL-1β release from macrophages.

Luheshi Nadia M NM Giles James A JA Lopez-Castejon Gloria G Brough David D

European journal of immunology 20111227 3

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that regulates inflammatory responses to injury and infection. IL-1β secretion requires the protease caspase-1, which is activated following recruitment to inflammasomes. Endogenous danger-associated molecular patterns (DAMPs) released from necrotic cells activate caspase-1 through an NLRP3-inflammasome. Here, we show that the endogenous lipid metabolite sphingosine (Sph) acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion o ...[more]

PMID: 22105559

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Dataset Information

Sphingosine regulates the NLRP3-inflammasome and IL-1? release from macrophages.

Publications

Sphingosine regulates the NLRP3-inflammasome and IL-1β release from macrophages.

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