| Cutting edge: TNF-alpha-converting enzyme (TACE/ADAM17) inactivation in mouse myeloid cells prevents lethality from endotoxin shock. | |
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MedLine Citation:
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PMID: 17709479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TNF-alpha, a potent proinflammatory cytokine, is synthesized as a membrane-anchored precursor and proteolytically released from cells. Soluble TNF is the primary mediator of pathologies such as rheumatoid arthritis, Crohn's disease, and endotoxin shock. The TNF-alpha converting enzyme (TACE), a disintegrin and metalloprotease 17 (ADAM17), has emerged as the best candidate TNF sheddase, but other proteinases can also release TNF. Because TACE-deficient mice die shortly after birth, we generated conditional TACE-deficient mice to address whether TACE is the relevant sheddase for TNF in adult mice. In this study, we report that TACE inactivation in myeloid cells or temporal inactivation at 6 wk offers strong protection from endotoxin shock lethality in mice by preventing increased TNF serum levels. These findings corroborate that TACE is the major endotoxin-stimulated TNF sheddase in mouse myeloid cells in vivo, thereby further validating TACE as a principal target for the treatment of TNF-dependent pathologies. |
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Authors:
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Keisuke Horiuchi; Tokuhiro Kimura; Takeshi Miyamoto; Hironari Takaishi; Yasunori Okada; Yoshiaki Toyama; Carl P Blobel |
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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 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 179 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-21 Completed Date: 2007-11-20 Revised Date: 2011-09-22 |
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: 2686-9 Citation Subset: AIM; IM |
Affiliation:
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Arthritis and Tissue Degeneration Program, Hospital for Special Surgery, Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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ADAM Proteins
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antagonists & inhibitors*,
genetics Animals GTP-Binding Proteins / genetics Integrases / genetics Mice Mice, Mutant Strains Myeloid Cells / enzymology* Shock, Septic / enzymology, prevention & control* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM 64750/GM/NIGMS NIH HHS; R01 GM064750-09/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/myxovirus resistance proteins; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases; EC 3.4.24.-/ADAM Proteins; EC 3.4.24.-/tumor necrosis factor-alpha convertase; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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