Zinc modulates mRNA levels of cytokines

Bin Bao1, Ananda S Prasad, Frances W J Beck

  • 1Internal Medicine Department, Wayne State University Medical School, Detroit, MI 48201, USA.

Insights

Zinc deficiency impairs immune cell function, decreasing IL-2 and IFN-gamma in T-helper cells while increasing TNF-alpha, IL-1 beta, and IL-8 in monocytes. Zinc

Area of Science:

  • Immunology
  • Molecular Biology
  • Nutritional Science

Background:

  • Zinc is crucial for cell-mediated immunity.
  • Zinc deficiency impairs immune responses, leading to infections and altered cytokine production.
  • Specific effects of zinc on cytokine gene expression in different immune cell types are not fully understood.

Purpose of the Study:

  • To investigate the impact of zinc deficiency on the expression of key cytokines (IL-2, IFN-gamma, TNF-alpha, IL-1 beta, IL-8) in distinct immune cell lineages.
  • To determine if zinc deficiency affects cytokine gene expression or mRNA stability.
  • To elucidate the cell lineage-specific role of zinc in cytokine regulation.

Main Methods:

  • Utilized HUT-78 (Th0), D1.1 (Th1), and HL-60 (monocyte-macrophage) cell lines.
  • Compared cytokine and mRNA levels in zinc-deficient versus zinc-sufficient cells following specific stimulations (PMA/PHA, PHA/ionomycin).
  • Employed Actinomycin D to assess the effect of zinc on cytokine mRNA stability.

Main Results:

  • Zinc deficiency significantly decreased Interleukin-2 (IL-2) and Interferon-gamma (IFN-gamma) levels and mRNAs in Th0 and Th1 cell lines.
  • Conversely, zinc deficiency elevated Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin-1 beta (IL-1 beta), and Interleukin-8 (IL-8) levels and mRNAs in the monocyte-macrophage cell line.
  • Actinomycin D studies indicated that zinc influences cytokine gene expression rather than mRNA stability.

Conclusions:

  • Zinc positively regulates the gene expression of IL-2 and IFN-gamma in T-helper (Th1) cells.
  • Zinc negatively regulates the gene expression of TNF-alpha, IL-1 beta, and IL-8 in monocyte-macrophage cells.
  • The influence of zinc on cytokine gene expression is specific to the immune cell lineage.

Related Concept Videos

MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
Chromatin Structure Regulates pre-mRNA Processing02:41

Chromatin Structure Regulates pre-mRNA Processing

In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...