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.