| Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells. | |
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MedLine Citation:
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PMID: 21439265 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-03-23 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 407 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-04-25 Completed Date: 2011-07-19 Revised Date: 2012-09-24 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 703-7 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, USA. bbao@med.wayne.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation*
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drug effects,
genetics Cell Line Concanavalin A / pharmacology Humans Interferon-gamma / biosynthesis*, genetics Receptors, Interleukin-12 / biosynthesis*, genetics T-Box Domain Proteins / biosynthesis*, genetics Th1 Cells / cytology, immunology* Up-Regulation Zinc / deficiency, metabolism*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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5R01A150698-04//PHS HHS; R01 AI050698-01A1/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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