Evidence for reprogramming global gene expression during zinc deficiency in the HUT-78 cell line.
OBJECTIVE
Investigations using cell lines, primary cells, animal models, and human subjects have provided data to indicate that zinc-deficient conditions affect immune functioning of myeloid and lymphoid cells. We hypothesized that zinc-deficient conditions alone may induce the expression of genes in lymphoid cells, which favor enhanced responses to myeloid molecules even in the absence of myeloid cells or myeloid factors. Our objective was to investigate the effects of low zinc-induced alterations in gene expression in a single lymphoid cell line in the absence of influences from growth factors and/or cytokines generated by other cell types also being affected by low zinc status.


METHODS
Microarray analysis of non-stimulated and phytohemagglutinin-p/phorbol 12-myristate 13-acetate-stimulated zinc-deficient and zinc-adequate human-derived HUT-78 (TH(0)) lymphoblasts was used to identify changes in gene expressions associated solely with zinc-deficient status in these cells.


RESULTS
Overall, gene expression for molecules that would increase T-lymphocyte response to signals from myeloid cells such as cytokine receptors and selected adhesion molecules were upregulated, whereas those associated with T-lymphocyte-directed immune functions, interleukin-2 and interleukin-6 receptors, the cytokine interleukin-4, and zinc finger transcription factors were downregulated. Analysis of selected data obtained from healthy, but mildly zinc-deficient human subjects corroborated observations obtained from low zinc-altered gene expression in HUT-78 cells.


CONCLUSIONS
These data provide evidence for a shift in gene expression of molecules that would increase lymphoid responses to myeloid driven pathways during periods of zinc deficiency even in the absence of myeloid-derived stimuli.
Beck
Frances W J
FW
Department of Internal Medicine, Division of Hematology, Wayne State University School of Medicine, Detroit, Michigan, USA. fwbeck@med.wayne.edu
Li
Yiwei
Y
Bao
Bin
B
Prasad
Ananda S
AS
Sarkar
Fazlul H
FH
D002453:Cell Cycle / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004198:Disease Susceptibility; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism*; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D016335:Zinc Fingers
D016207:Cytokines; D015032:Zinc