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- Publisher Website: 10.4049/jimmunol.176.2.721
- Scopus: eid_2-s2.0-30744471132
- PMID: 16393953
- WOS: WOS:000234553800007
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Article: Cutting edge: Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation
Title | Cutting edge: Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation |
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Authors | |
Issue Date | 2006 |
Citation | Journal of Immunology, 2006, v. 176, n. 2, p. 721-725 How to Cite? |
Abstract | Host response to infectious agents must be rapid and powerful. One mechanism is the release of presynthesized membrane-bound TNF. TNF shedding is mediated by TNF-α converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3). We show that loss of TIMP3 impacts innate immunity by dysregulating cleavage of TNF and its receptors. Cultured timp3-/- macrophages release more TNF in response to LPS than wild-type macrophages. In timp3-/- mice, LPS causes serum levels of TNF and its receptors to rise more rapidly and remain higher compared with wild-type mice. The altered kinetics of ligand and receptor shedding enhances TNF signaling in timp3-/- mice, indicated by elevated serum IL-6. Physiologically, timp3-/- mice are more susceptible to LPS-induced mortality. Ablation of the TNF receptor gene p55 (Tnfrsf1a) or treatment with a synthetic metalloproteinase inhibitor rescues timp3-/- mice. Thus, TIMP3 is essential for normal innate immune function. Copyright © 2006 by The American Association of Immunologists, Inc. |
Persistent Identifier | http://hdl.handle.net/10722/292557 |
ISSN | 2022 Impact Factor: 4.4 2020 SCImago Journal Rankings: 2.737 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Smookler, David S. | - |
dc.contributor.author | Mohammed, Fazilat F. | - |
dc.contributor.author | Kassiri, Zamaneh | - |
dc.contributor.author | Duncan, Gordon S. | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Khokha, Rama | - |
dc.date.accessioned | 2020-11-17T14:56:44Z | - |
dc.date.available | 2020-11-17T14:56:44Z | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | Journal of Immunology, 2006, v. 176, n. 2, p. 721-725 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.uri | http://hdl.handle.net/10722/292557 | - |
dc.description.abstract | Host response to infectious agents must be rapid and powerful. One mechanism is the release of presynthesized membrane-bound TNF. TNF shedding is mediated by TNF-α converting enzyme, which is selectively inhibited by the tissue inhibitor of metalloproteinase 3 (TIMP3). We show that loss of TIMP3 impacts innate immunity by dysregulating cleavage of TNF and its receptors. Cultured timp3-/- macrophages release more TNF in response to LPS than wild-type macrophages. In timp3-/- mice, LPS causes serum levels of TNF and its receptors to rise more rapidly and remain higher compared with wild-type mice. The altered kinetics of ligand and receptor shedding enhances TNF signaling in timp3-/- mice, indicated by elevated serum IL-6. Physiologically, timp3-/- mice are more susceptible to LPS-induced mortality. Ablation of the TNF receptor gene p55 (Tnfrsf1a) or treatment with a synthetic metalloproteinase inhibitor rescues timp3-/- mice. Thus, TIMP3 is essential for normal innate immune function. Copyright © 2006 by The American Association of Immunologists, Inc. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Immunology | - |
dc.title | Cutting edge: Tissue inhibitor of metalloproteinase 3 regulates TNF-dependent systemic inflammation | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.4049/jimmunol.176.2.721 | - |
dc.identifier.pmid | 16393953 | - |
dc.identifier.scopus | eid_2-s2.0-30744471132 | - |
dc.identifier.volume | 176 | - |
dc.identifier.issue | 2 | - |
dc.identifier.spage | 721 | - |
dc.identifier.epage | 725 | - |
dc.identifier.isi | WOS:000234553800007 | - |
dc.identifier.issnl | 0022-1767 | - |