| Protective role of interleukin-17 in murine NKT cell-driven acute experimental hepatitis. | |
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MedLine Citation:
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PMID: 20847291 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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NKT cells are highly enriched within the liver. On activation NKT cells rapidly release large quantities of different cytokines which subsequently activate, recruit, or modulate cells important for the development of hepatic inflammation. Recently, it has been demonstrated that NKT cells can also produce interleukin-17 (IL-17), a proinflammatory cytokine that is also known to have diverse immunoregulatory effects. The role played by IL-17 in hepatic inflammation is unclear. Here we show that during α-galactosylceramide (αGalCer)-induced hepatitis in mice, a model of hepatitis driven by specific activation of the innate immune system via NKT cells within the liver, NK1.1+ and CD4+ iNKT cells rapidly produce IL-17 and are the main IL-17-producing cells within the liver. Administration of IL-17 neutralizing monoclonal antibodies before αGalCer injection significantly exacerbated hepatitis, in association with a significant increase in hepatic neutrophil and proinflammatory monocyte (ie, producing IL-12, tumor necrosis factor-α) recruitment, and increased hepatic mRNA and protein expression for the relevant neutrophil and monocyte chemokines CXCL5/LIX and CCL2/MCP-1, respectively. In contrast, administration of exogenous recombinant murine IL-17 before α-GalCer injection ameliorated hepatitis and inhibited the recruitment of inflammatory monocytes into the liver. Our results demonstrate that hepatic iNKT cells specifically activated with α-GalCer rapidly produce IL-17, and IL-17 produced after α-GalCer administration inhibits the development of hepatitis. |
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Authors:
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Zenebech Wondimu; Tania Santodomingo-Garzon; Tai Le; Mark G Swain |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-16 |
Journal Detail:
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Title: The American journal of pathology Volume: 177 ISSN: 1525-2191 ISO Abbreviation: Am. J. Pathol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-04 Completed Date: 2011-03-21 Revised Date: 2011-11-01 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 2334-46 Citation Subset: AIM; IM |
Affiliation:
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Immunology Research Group, Health Sciences Center, University of Calgary, 3330 Hospital Dr., NW, Calgary, Alberta, Canada, T2N 4N1. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chemokines / genetics, immunology Disease Models, Animal Drug-Induced Liver Injury / immunology*, pathology Galactosylceramides / pharmacology Interleukin-17 / immunology* Interleukin-8 / genetics, immunology Liver / cytology, immunology, pathology Male Mice Mice, Inbred C57BL Monocytes / immunology Natural Killer T-Cells / cytology, immunology* Neutrophils / immunology |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Chemokines; 0/Galactosylceramides; 0/Interleukin-17; 0/Interleukin-8; 0/alpha-galactosylceramide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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