Back to Search Start Over

Intracellular free zinc up-regulates IFN-γ and T-bet essential for Th1 differentiation in Con-A stimulated HUT-78 cells

Authors :
Ginny Bao
Shadan Ali
Bin Bao
Fazlul H. Sarkar
Frances W.J. Beck
Ananda S. Prasad
Tapinder Singh
Source :
Biochemical and Biophysical Research Communications. 407:703-707
Publication Year :
2011
Publisher :
Elsevier BV, 2011.

Abstract

Zinc deficiency impairs cellular immunity. Up-regulation of mRNA levels of IFN-γ, IL-12Rβ2, and T-bet are essential for Th1 differentiation. We hypothesized that zinc increases Th1 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 Th0 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 (a Th0 cell line), 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 5 μM zinc medium showed a greater sustained increase in intracellular free zinc in comparison to cells incubated in 1 μM 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-12Rbβ2 mRNAs required for Th1 cell differentiation. These results suggest that zinc increase Th1 cell differentiation by up-regulation of IFN-γ and T-bet, and IL-12Rbβ2 mRNAs.

Details

ISSN :
0006291X
Volume :
407
Database :
OpenAIRE
Journal :
Biochemical and Biophysical Research Communications
Accession number :
edsair.doi.dedup.....8c2c67c052789f3934bbc4ddc6fb6026
Full Text :
https://doi.org/10.1016/j.bbrc.2011.03.084