Zinc up-regulates NF-kappaB activation via phosphorylation of IkappaB in HUT-78 (Th0) cells.
Nuclear factor of kappaB (NF-kappaB) is a major transcription factor regulating the expression of interleukin-2 (IL-2) and interleukin-2 receptor-alpha (IL-2Ralpha) in Th(1) cells. We previously demonstrated that zinc increased IL-2 and IL-2Ralpha production via NF-kappaB activation in HUT-78 (Th(0)) cells. However, the molecular mechanism is not well understood. In this study, we found that zinc increased phosphorylated IkappaB-alpha, NF-kappaB translocation and activation, as well as the production of IL-2 and IL-2Ralpha in wild type IkappaB gene transfected zinc-sufficient HUT-78 cells, compared to zinc-deficient HUT-78 cells. However, dominant negative IkappaB gene expression decreased these parameters in zinc-sufficient cells, suggesting that zinc increased NF-kappaB activation via IkappaB pathway.
Bao
Bin
B
Department of Internal Medicine, Wayne State University School of Medicine, 2221 Elliman Building, 421 E. Canfield, Detroit, MI, USA. bbao@med.wayne.edu
Prasad
Ananda S
AS
Beck
Frances W J
FW
Sarkar
Fazlul H
FH
D015153:Blotting, Western; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D014162:Transfection; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
D020672:I-kappa B Proteins; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B; D015032:Zinc