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A Feedback Loop between Inflammation and Zn Uptake

OBJECTIVE: Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a mo...

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Autores principales: Bonaventura, Paola, Lamboux, Aline, Albarède, Francis, Miossec, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741903/
https://www.ncbi.nlm.nih.gov/pubmed/26845700
http://dx.doi.org/10.1371/journal.pone.0147146
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author Bonaventura, Paola
Lamboux, Aline
Albarède, Francis
Miossec, Pierre
author_facet Bonaventura, Paola
Lamboux, Aline
Albarède, Francis
Miossec, Pierre
author_sort Bonaventura, Paola
collection PubMed
description OBJECTIVE: Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. METHODS: Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike (70)Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. RESULTS: Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. CONCLUSION: IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations.
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spelling pubmed-47419032016-02-11 A Feedback Loop between Inflammation and Zn Uptake Bonaventura, Paola Lamboux, Aline Albarède, Francis Miossec, Pierre PLoS One Research Article OBJECTIVE: Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. METHODS: Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike (70)Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. RESULTS: Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. CONCLUSION: IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations. Public Library of Science 2016-02-04 /pmc/articles/PMC4741903/ /pubmed/26845700 http://dx.doi.org/10.1371/journal.pone.0147146 Text en © 2016 Bonaventura et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Bonaventura, Paola
Lamboux, Aline
Albarède, Francis
Miossec, Pierre
A Feedback Loop between Inflammation and Zn Uptake
title A Feedback Loop between Inflammation and Zn Uptake
title_full A Feedback Loop between Inflammation and Zn Uptake
title_fullStr A Feedback Loop between Inflammation and Zn Uptake
title_full_unstemmed A Feedback Loop between Inflammation and Zn Uptake
title_short A Feedback Loop between Inflammation and Zn Uptake
title_sort feedback loop between inflammation and zn uptake
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741903/
https://www.ncbi.nlm.nih.gov/pubmed/26845700
http://dx.doi.org/10.1371/journal.pone.0147146
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