| An inflammasome-independent role for epithelial-expressed Nlrp3 in renal ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 20962258 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cytoplasmic innate immune receptors are important therapeutic targets for diseases associated with overproduction of proinflammatory cytokines. One cytoplasmic receptor complex, the Nlrp3 inflammasome, responds to an extensive array of molecules associated with cellular stress. Under normal conditions, Nlrp3 is autorepressed, but in the presence of its ligands, it oligomerizes, recruits apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc), and triggers caspase 1 activation and the maturation of proinflammatory cytokines such as IL-1β and IL-18. Because ischemic tissue injury provides a potential source for Nlrp3 ligands, our study compared and contrasted the effects of renal ischemia in wild-type mice and mice deficient in components of the Nlrp3 inflammasome (Nlrp3(-/-) and Asc(-/-) mice). To examine the role of the inflammasome in renal ischemia-reperfusion injury (IRI) we also tested its downstream targets caspase 1, IL-1β, and IL-18. Both Nlrp3 and Asc were highly expressed in renal tubular epithelium of humans and mice, and the absence of Nlrp3, but not Asc or the downstream inflammasome targets, dramatically protected from kidney IRI. We conclude that Nlrp3 contributes to renal IRI by a direct effect on renal tubular epithelium and that this effect is independent of inflammasome-induced proinflammatory cytokine production. |
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Authors:
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Alana A Shigeoka; James L Mueller; Amanpreet Kambo; John C Mathison; Andrew J King; Wesley F Hall; Jean da Silva Correia; Richard J Ulevitch; Hal M Hoffman; Dianne B McKay |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-10-20 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2010-12-02 Revised Date: 2011-12-14 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6277-85 Citation Subset: AIM; IM |
Affiliation:
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Department of Immunology and Microbial Sciences, The Scripps Research Institute, La Jolla, CA 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acute Kidney Injury
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immunology,
metabolism* Animals Apoptosis / immunology Carrier Proteins / immunology, metabolism* Caspase 1 / immunology, metabolism Cells, Cultured Cytokines / metabolism Cytoskeletal Proteins / immunology, metabolism Enzyme-Linked Immunosorbent Assay Epithelial Cells / immunology, metabolism* Humans Immunoblotting In Situ Nick-End Labeling Inflammasomes / immunology, metabolism* Kidney Tubules Mice Mice, Knockout Reperfusion Injury / immunology, metabolism* Reverse Transcriptase Polymerase Chain Reaction |
| Grant Support | |
ID/Acronym/Agency:
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1R01DK60151/DK/NIDDK NIH HHS; 1UL1RR025774/RR/NCRR NIH HHS; R01 DK075718-03/DK/NIDDK NIH HHS; R01 DK075718-04/DK/NIDDK NIH HHS; R01 DK075718-05/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CIAS1 protein, mouse; 0/Carrier Proteins; 0/Cytokines; 0/Cytoskeletal Proteins; 0/Inflammasomes; 0/Pycard protein, mouse; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
Erratum In:
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J Immunol. 2011 Feb 1;186(3):1880 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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