| Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α. | |
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MedLine Citation:
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PMID: 22017873 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1α is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine. |
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Authors:
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Inna S Afonina; Graham A Tynan; Susan E Logue; Sean P Cullen; Michael Bots; Alexander U Lüthi; Emer P Reeves; Noel G McElvaney; Jan P Medema; Ed C Lavelle; Seamus J Martin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular cell Volume: 44 ISSN: 1097-4164 ISO Abbreviation: Mol. Cell Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-24 Completed Date: 2011-12-30 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 265-78 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / immunology, metabolism Granzymes / metabolism* HeLa Cells Human Umbilical Vein Endothelial Cells Humans Inflammation / immunology, metabolism Interleukin-1alpha / metabolism* Mice Mice, Inbred BALB C Proteolysis |
| Grant Support | |
ID/Acronym/Agency:
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082749//Wellcome Trust; 082749//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukin-1alpha; EC 3.4.21.-/Granzymes |
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