Document Detail

Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells.
MedLine Citation:
PMID:  21439265     Owner:  NLM     Status:  MEDLINE    
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.
Bin Bao; Ananda S Prasad; Frances W J Beck; Ginny W Bao; Tapinder Singh; Shadan Ali; Fazlul H Sarkar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-23
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  407     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-25     Completed Date:  2011-07-19     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  703-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA.
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MeSH Terms
Cell Differentiation* / drug effects,  genetics
Cell Line
Concanavalin A / pharmacology
Interferon-gamma / biosynthesis*,  genetics
Receptors, Interleukin-12 / biosynthesis*,  genetics
T-Box Domain Proteins / biosynthesis*,  genetics
Th1 Cells / cytology,  immunology*
Zinc / deficiency,  metabolism*,  pharmacology
Grant Support
5R01A150698-04//PHS HHS; R01 AI050698-01A1/AI/NIAID NIH HHS
Reg. No./Substance:
0/IL12RB2 protein, human; 0/Receptors, Interleukin-12; 0/T-Box Domain Proteins; 0/T-box transcription factor TBX21; 11028-71-0/Concanavalin A; 7440-66-6/Zinc; 82115-62-6/Interferon-gamma

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