| Type I interferon inhibits interleukin-1 production and inflammasome activation. | |
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MedLine Citation:
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PMID: 21349431 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Type I interferon (IFN) is a common therapy for autoimmune and inflammatory disorders, yet the mechanisms of action are largely unknown. Here we showed that type I IFN inhibited interleukin-1 (IL-1) production through two distinct mechanisms. Type I IFN signaling, via the STAT1 transcription factor, repressed the activity of the NLRP1 and NLRP3 inflammasomes, thereby suppressing caspase-1-dependent IL-1β maturation. In addition, type I IFN induced IL-10 in a STAT1-dependent manner; autocrine IL-10 then signaled via STAT3 to reduce the abundance of pro-IL-1α and pro-IL-1β. In vivo, poly(I:C)-induced type I IFN diminished IL-1β production in response to alum and Candida albicans, thus increasing susceptibility to this fungal pathogen. Importantly, monocytes from multiple sclerosis patients undergoing IFN-β treatment produced substantially less IL-1β than monocytes derived from healthy donors. Our findings may thus explain the effectiveness of type I IFN in the treatment of inflammatory diseases but also the observed "weakening" of the immune system after viral infection. |
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Authors:
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Greta Guarda; Marion Braun; Francesco Staehli; Aubry Tardivel; Chantal Mattmann; Irmgard Förster; Matthias Farlik; Thomas Decker; Renaud A Du Pasquier; Pedro Romero; Jürg Tschopp |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Immunity Volume: 34 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 213-23 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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