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.
Abstract:
Zinc plays an important role in cell-mediated immune function. Altered cellular immune response resulting from zinc deficiency leads to frequent microbial infections, thymic atrophy, decreased natural killer activity, decreased thymic hormone activity, and altered cytokine production. In this study, we examined the effect of zinc deficiency on IL-2 and IFN-gamma in HUT-78 (Th0) and D1.1 (Th1) cell lines and TNF-alpha, IL-1 beta, and IL-8 in the HL-60 (monocyte-macrophage) cell line. The results demonstrate that zinc deficiency decreased the levels of IL-2 and IFN-gamma cytokines and mRNAs in HUT-78 after 6 h of PMA/p-phytohemagglutinin (PHA) stimulation and in D1.1 cells after 6 h of PHA/ionomycin stimulation compared with the zinc-sufficient cells. However, zinc deficiency increased the levels of TNF-alpha, IL-1 beta, and IL-8 cytokines and mRNAs in HL-60 cells after 6 h of PMA stimulation compared with zinc-sufficient cells. Actinomycin D study suggests that the changes in the levels of these cytokine mRNAs were not the result of the stability affected by zinc but might be the result of altered expression of these cytokine genes. These data demonstrate that zinc mediates positively the gene expression of IL-2 and IFN-gamma in the Th1 cell line and negatively TNF-alpha, IL-1 beta, and IL-8 in the monocyte-macrophage cell line. Our study shows that the effect of zinc on gene expression and production of cytokines is cell lineage specific.
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