title: Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells.
abstract: Zinc deficiency impairs cellular immunity. Up-regulation of mRNA levels of IFN-γ, IL-12Rβ2, and T-bet are essential for Th(1) differentiation. We hypothesized that zinc increases Th(1) differentiation via up-regulation of IFN-γ and T-bet expression. To test this hypothesis, we used zinc-deficient and zinc-sufficient HUT-78 cells (a Th(0) cell line) under different condition of stimulation in this study. We also used TPEN, a zinc-specific chelator, to decrease the bioavailability of zinc in the cells. We measured intracellular free zinc, cytokines, and the mRNAs of T-bet, IFN-γ, and IL-12Rβ2. In this study, we show that in zinc-sufficient HUT-78 cells, mRNA levels of IFN-γ, IL-12Rβ2, and T-bet in PMA/PHA-stimulated cells were increased in comparison to zinc-deficient cells. Although intracellular free zinc was increased slightly in PMA/PHA-stimulated cells, Con-A-stimulated cells in 5μM zinc medium showed a greater sustained increase in intracellular free zinc in comparison to cells incubated in 1μM zinc. The cells pre-incubated with TPEN showed decreased mRNA levels of IFN-γ and T-bet mRNAs in comparison to cells without TPEN incubation. We conclude that stimulation of cells by Con-A via TCR, release intracellular free zinc which functions as a signal molecule for generation of IFN-γ and T-bet, and IL-12Rβ2 mRNAs required for Th(1) cell differentiation. These results suggest that zinc increase Th(1) cell differentiation by up-regulation of IFN-γ and T-bet, and IL-12Rbβ2 mRNAs.
authors: Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA. bbao@med.wayne.edu
authors: Bin
authors: B
authors: Bao
authors: Ananda S
authors: AS
authors: Prasad
authors: Frances W J
authors: FW
authors: Beck
authors: Ginny W
authors: GW
authors: Bao
authors: Tapinder
authors: T
authors: Singh
authors: Shadan
authors: S
authors: Ali
authors: Fazlul H
authors: FH
authors: Sarkar
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation; D015032:Zinc / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D000098815:T-bet Transcription Factor
chemical_list: C508439:IL12RB2 protein, human; D053707:Receptors, Interleukin-12; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D003208:Concanavalin A; D007371:Interferon-gamma; D015032:Zinc