Zinc activates NF-kappaB in HUT-78 cells.

Zinc is essential for human health, and its deficiency in human beings results in growth failure, immune disorders affecting Th1 functions, decreased interleukin-2 (IL-2) production, and cognitive impairment. Nearly 2000 transcription factors require zinc for their structural integrity; however, it is not known whether cellular zinc deficiency results in any change in activation of any of the transcription factors. Inasmuch as NF-kappaB binds to the promoter enhancer area of IL-2 and IL-2Ralpha genes, we investigated the effect of zinc deficiency on activation of NF-kappaB and its binding to DNA in HUT-78, a Th0 malignant human lymphoblastoid cell line. We show here for the first time that in zinc-deficient HUT-78 cells, phosphorylated IkappaB, and IKK, ubiquitinated IkappaB and binding of NF-kappaB to DNA were all significantly decreased. Zinc increased the translocation of NF-kappaB from cytosol to nucleus. We also demonstrate that the binding of recombinant NF-kappaB (p50)(2) to DNA in HUT-78 cells was zinc specific. We conclude that zinc plays an important role in the activation of NF-kappaB in HUT-78 cells.