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A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock
Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is centrally involved in several inflammatory disorders. Administration of TNF leads to a potentially lethal systemic inflammatory response syndrome (SIRS). We observed that (a) mice lacking functional genes for metallothionein 1 and 2...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2001
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193525/ https://www.ncbi.nlm.nih.gov/pubmed/11733576 |
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author | Waelput, Wim Broekaert, Daniël Vandekerckhove, Joël Brouckaert, Peter Tavernier, Jan Libert, Claude |
author_facet | Waelput, Wim Broekaert, Daniël Vandekerckhove, Joël Brouckaert, Peter Tavernier, Jan Libert, Claude |
author_sort | Waelput, Wim |
collection | PubMed |
description | Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is centrally involved in several inflammatory disorders. Administration of TNF leads to a potentially lethal systemic inflammatory response syndrome (SIRS). We observed that (a) mice lacking functional genes for metallothionein 1 and 2 (MT-null) were protected compared with wild-type controls (P = 0.0078), and (b) mice overexpressing MT-1 (MT-TG) were more sensitized for the lethal effect of TNF than control mice (P = 0.0003), indicating a mediating role for MT in TNF induced SIRS. As MT is involved in the body zinc homeostasis, we tested whether zinc-deprivation or -supplementation alters the response to TNF. Although zinc-depletion strongly sensitized (P = 0.036), and pretreatment with zinc sulfate (ZnSO(4)) conferred protection against the deleterious effects of TNF (P < 0.0002), it was also found that the protection provided by zinc is independent of MT. Our observation that hsp70 is strongly induced in jejunum after ZnSO(4) treatment, suggests a contribution of hsp70 in the protection against TNF. In addition, ZnSO(4) cotreatment allowed complete regression of inoculated tumors with TNF and interferon γ, leading to a significantly better survival (P = 0.0045). |
format | Text |
id | pubmed-2193525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2001 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21935252008-04-14 A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock Waelput, Wim Broekaert, Daniël Vandekerckhove, Joël Brouckaert, Peter Tavernier, Jan Libert, Claude J Exp Med Brief Definitive Report Tumor necrosis factor (TNF) is a proinflammatory cytokine, which is centrally involved in several inflammatory disorders. Administration of TNF leads to a potentially lethal systemic inflammatory response syndrome (SIRS). We observed that (a) mice lacking functional genes for metallothionein 1 and 2 (MT-null) were protected compared with wild-type controls (P = 0.0078), and (b) mice overexpressing MT-1 (MT-TG) were more sensitized for the lethal effect of TNF than control mice (P = 0.0003), indicating a mediating role for MT in TNF induced SIRS. As MT is involved in the body zinc homeostasis, we tested whether zinc-deprivation or -supplementation alters the response to TNF. Although zinc-depletion strongly sensitized (P = 0.036), and pretreatment with zinc sulfate (ZnSO(4)) conferred protection against the deleterious effects of TNF (P < 0.0002), it was also found that the protection provided by zinc is independent of MT. Our observation that hsp70 is strongly induced in jejunum after ZnSO(4) treatment, suggests a contribution of hsp70 in the protection against TNF. In addition, ZnSO(4) cotreatment allowed complete regression of inoculated tumors with TNF and interferon γ, leading to a significantly better survival (P = 0.0045). The Rockefeller University Press 2001-12-03 /pmc/articles/PMC2193525/ /pubmed/11733576 Text en Copyright © 2001, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Waelput, Wim Broekaert, Daniël Vandekerckhove, Joël Brouckaert, Peter Tavernier, Jan Libert, Claude A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title | A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title_full | A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title_fullStr | A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title_full_unstemmed | A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title_short | A Mediator Role For Metallothionein in Tumor Necrosis Factor–induced Lethal Shock |
title_sort | mediator role for metallothionein in tumor necrosis factor–induced lethal shock |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193525/ https://www.ncbi.nlm.nih.gov/pubmed/11733576 |
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