| Inflammasome activation and IL-1{beta} target IL-1{alpha} for secretion as opposed to surface expression. | |
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MedLine Citation:
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PMID: 22006336 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Interleukin-1α (IL-1α) and -β both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)-IL-1α and pro-IL-1β is induced by Toll-like receptor (TLR)-mediated NF-κB activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1β. The regulation of IL-1α maturation and secretion, however, remains elusive. IL-1α exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1α, the surface and secreted form, are differentially regulated. Surface IL-1α requires NF-κB activation only, whereas secretion of mature IL-1α requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1α also required the presence of IL-1β, as demonstrated in IL-1β-deficient mice. We further demonstrate that IL-1β directly binds IL-1α, thus identifying IL-1β as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases. |
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Authors:
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Antonia Fettelschoss; Magdalena Kistowska; Salomé Leibundgut-Landmann; Hans-Dietmar Beer; Pål Johansen; Gabriela Senti; Emmanuel Contassot; Martin F Bachmann; Lars E French; Annette Oxenius; Thomas M Kündig |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-17 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: - ISSN: 1091-6490 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Dermatology, Zurich University Hospital, 8091 Zurich, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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