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Am J Physiol Endocrinol Metab (June 17, 2003). doi:10.1152/ajpendo.00545.2002
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Submitted on December 13, 2002
Accepted on May 31, 2003

Zinc modulates mRNA levels of IL-2 and IFN-{gamma} positively in HUT-78 and D1.1 cells and negatively mRNA levels of TNF-{alpha}, IL-1 {beta}, and IL-8 in HL-60 cells

Bin Bao1, Ananda S Prasad1*, Frances W J Beck1, and Michele Godmere1

1 Hematology/Oncology Division, Internal Medicine Department, Wayne State University Medical School, Detroit, Michigan, USA

* To whom correspondence should be addressed. E-mail: prasada{at}karmanos.org.

Zinc plays an important role in cell-mediated immune function. Altered cellular immune response due to zinc deficiency leads to frequent microbial infections, thymic atrophy, decreased NK 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 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 6h of PMA/PHA stimulatin and in D1.1 cells after 6h of PHA /ionomycin stimulation compared to the zinc sufficient cells. However, zinc deficiency increased the levels of TNF-{alpha}, IL-1 {beta}, and IL-8 cytokines and mRNAs in HL60 cells after 6 h of PMA stimulation, compared to zinc sufficient cells. Actinomycin D study suggests that the changes in the levels of these cytokine mRNAs were not due to the stability affected by zinc, but might be due to the altered expression of these cytokine genes. These data demonstrate that zinc mediates positively the gene expression of IL-2 and IFN-{gamma} in Th1 cell line, and negatively TNF-{alpha}, IL-1 {beta}, and IL-8 in monocyte-macrophage cell line. Our study shows that the effect of zinc on the gene expression and production of cytokines is cell-lineage specific.




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