| Sphingosine regulates the NLRP3-inflammasome and IL-1β release from macrophages. | |
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MedLine Citation:
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PMID: 22105559 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 a NLRP3-inflammasome. Here we show that the endogenous lipid metabolite sphingosine acts as a DAMP by inducing the NLRP3-inflammasome-dependent secretion of IL-1β from macrophages. This process was dependent upon serine/threonine protein phosphatases since the PP1/PP2A inhibitors okadaic acid and calyculin A inhibited sphingosine-induced IL-1β release. IL-1β 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 sphingosine 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. |
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Authors:
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Nadia M Luheshi; James A Giles; Gloria Lopez-Castejon; David Brough |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-22 |
Journal Detail:
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Title: European journal of immunology Volume: - ISSN: 1521-4141 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-22 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Faculty of Life Sciences, University of Manchester, AV Hill Building, Oxford Road, Manchester, M13 9PT, U.K. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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