Zinc deficiency impairs interferon-γ production on post-transcriptional level.
Gene regulation
Interferon-gamma
Zinc
Journal
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
ISSN: 1878-3252
Titre abrégé: J Trace Elem Med Biol
Pays: Germany
ID NLM: 9508274
Informations de publication
Date de publication:
Dec 2020
Dec 2020
Historique:
received:
17
02
2020
revised:
12
06
2020
accepted:
15
06
2020
pubmed:
10
7
2020
medline:
28
9
2021
entrez:
10
7
2020
Statut:
ppublish
Résumé
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. Zinc-deficient or -supplemented cell culture, ELISA, quantitative PCR, methylation analysis. 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. 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.
Sections du résumé
BACKGROUND
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
METHODS
Zinc-deficient or -supplemented cell culture, ELISA, quantitative PCR, methylation analysis.
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 32645654
pii: S0946-672X(20)30163-2
doi: 10.1016/j.jtemb.2020.126598
pii:
doi:
Substances chimiques
Interferon-gamma
82115-62-6
Zinc
J41CSQ7QDS
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
126598Informations de copyright
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