Zinc deficiency impairs interferon-γ production on post-transcriptional level
Copyright © 2020 Elsevier GmbH. All rights reserved..
BACKGROUND: Zinc is a trace element and is thus commonly known to be indispensable for regular cellular function. Until today, zinc deficiency is a widespread health problem, affecting approximately one sixth of the world's population. Especially the immune system has proven to be highly dependent on zinc. Interferon-γ (IFN-γ) is a key element in the defense against intracellular pathogens. A lack of this cytokine results in immunological impairment, whereas an excess can lead to autoimmunity, highlighting the importance of a well-regulated IFN-γ expression. In a state of zinc deficiency, the production of this cytokine has long been shown to be reduced. Providing further insight into the molecular mechanisms responsible for this interaction is the primary objective of this study.
METHODS: Zinc-deficient or -supplemented cell culture, ELISA, quantitative PCR, methylation analysis.
RESULTS: Promoter methylation is a typical mechanism of gene silencing and a strong regulating factor for IFN-γ production. An analysis of the methylation status of IFN-γ and its transcription factor IRF4 in human PBMC in a state of cellular zinc deficiency or excess showed no dependency on the trace metal. Unexpectedly, zinc-deficient PBMC, which secreted significantly less IFN-γ protein, showed significantly higher mRNA levels of the cytokine compared to cells with high total zinc levels.
CONCLUSION: This report is the first about this unconventional ratio of IFN-γ mRNA to protein. Such a mismatch is highly relevant to the study of protein production in general and that of IFN-γ in particular. Based on our results and the latest research, we hypothesize a strong post-transcriptional effect of zinc on IFN-γ.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) - 62(2020) vom: 15. Dez., Seite 126598 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rodenkirchen, Vera [VerfasserIn] |
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| Links: |
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| Themen: |
82115-62-6 |
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| Anmerkungen: |
Date Completed 27.09.2021 Date Revised 27.09.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jtemb.2020.126598 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier GmbH. All rights reserved. | ||
| 520 | |a BACKGROUND: Zinc is a trace element and is thus commonly known to be indispensable for regular cellular function. Until today, zinc deficiency is a widespread health problem, affecting approximately one sixth of the world's population. Especially the immune system has proven to be highly dependent on zinc. Interferon-γ (IFN-γ) is a key element in the defense against intracellular pathogens. A lack of this cytokine results in immunological impairment, whereas an excess can lead to autoimmunity, highlighting the importance of a well-regulated IFN-γ expression. In a state of zinc deficiency, the production of this cytokine has long been shown to be reduced. Providing further insight into the molecular mechanisms responsible for this interaction is the primary objective of this study | ||
| 520 | |a METHODS: Zinc-deficient or -supplemented cell culture, ELISA, quantitative PCR, methylation analysis | ||
| 520 | |a RESULTS: Promoter methylation is a typical mechanism of gene silencing and a strong regulating factor for IFN-γ production. An analysis of the methylation status of IFN-γ and its transcription factor IRF4 in human PBMC in a state of cellular zinc deficiency or excess showed no dependency on the trace metal. Unexpectedly, zinc-deficient PBMC, which secreted significantly less IFN-γ protein, showed significantly higher mRNA levels of the cytokine compared to cells with high total zinc levels | ||
| 520 | |a CONCLUSION: This report is the first about this unconventional ratio of IFN-γ mRNA to protein. Such a mismatch is highly relevant to the study of protein production in general and that of IFN-γ in particular. Based on our results and the latest research, we hypothesize a strong post-transcriptional effect of zinc on IFN-γ | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Gene regulation | |
| 650 | 4 | |a Interferon-gamma | |
| 650 | 4 | |a Zinc | |
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| 700 | 1 | |a Rink, Lothar |e verfasserin |4 aut | |
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