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.

中文翻译：

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缺锌会在转录后水平上损害干扰素-γ 的产生。

背景

锌是一种微量元素，因此众所周知，它对于正常的细胞功能是必不可少的。直到今天，缺锌仍是一个普遍存在的健康问题，影响着世界大约六分之一的人口。特别是免疫系统已被证明高度依赖锌。干扰素-γ (IFN-γ) 是防御细胞内病原体的关键因素。缺乏这种细胞因子会导致免疫损伤，而过量会导致自身免疫，突出了良好调节的 IFN-γ 表达的重要性。在缺锌状态下，这种细胞因子的产生早已被证明会减少。本研究的主要目标是进一步了解导致这种相互作用的分子机制。

方法

缺锌或补锌的细胞培养、ELISA、定量 PCR、甲基化分析。

结果

启动子甲基化是基因沉默的典型机制，也是 IFN-γ 产生的强调节因子。对处于细胞锌缺乏或过量状态的人 PBMC 中 IFN-γ 及其转录因子 IRF4 的甲基化状态的分析表明，对微量金属没有依赖性。出乎意料的是，与具有高总锌水平的细胞相比，分泌显着较少 IFN-γ 蛋白的缺锌 PBMC 显示出显着更高的细胞因子 mRNA 水平。

结论

这份报告是第一个关于 IFN-γ mRNA 与蛋白质的非常规比例的报告。这种错配与一般蛋白质生产的研究，特别是 IFN-γ 的研究高度相关。根据我们的结果和最新研究，我们假设锌对 IFN-γ 有很强的转录后效应。