Toxic effect of zinc on NF-kappaB, IL-2, IL-2 receptor alpha, and TNF-alpha in HUT-78 (Th(0)) cells.
Zinc deficiency decreased cellular immune response. Zinc supplementation reverses this response. High concentration of zinc intake is reported to alter immune response. We hypothesize that higher concentration of zinc adversely affects T-cell immune response. In this study, we examined whether higher concentration of zinc affects expression of IL-2, IL-2Ralpha, and TNF-alpha, and NF-kappaB activation in HUT-78 (Th(0)) cells. The results show that HUT-78 cells incubated in 15, 50, and 100 microM zinc medium had significantly higher intracellular zinc contents and faster growth after 4 days of incubation, compared to the cells incubated in 1 microM zinc medium. After PMA/PHA stimulation, 1 microM zinc showed significant decreases in NF-kappaB activation, and in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs compared to 15 microM zinc. The cells incubated in higher concentrations of zinc (50 and 100 microM zinc) showed mild to moderate decreases in the levels of IL-2, IL-2Ralpha, and TNF-alpha production and mRNAs, and in NF-kappaB activation compared to those incubated in 15 microM zinc medium. These data indicate that not only low level of zinc, but also high levels of zinc decrease Th1 function.
Bao
Bin
B
Division of Hematology/Oncology, Wayne State University Medical School, Detroit, MI 48201, USA. bbao@med.wayne.edu
Prasad
Ananda
A
Beck
Frances W J
FW
Suneja
Anupam
A
Sarkar
Fazlul
F
D015152:Blotting, Northern; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003470:Culture Media; D017930:Genes, Reporter; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007376:Interleukin-2 / Q000096:biosynthesis*; D053645:Interleukin-2 Receptor alpha Subunit; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015032:Zinc / Q000633:toxicity*
D003470:Culture Media; C508017:IL2RA protein, human; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D008156:Luciferases; D015032:Zinc