1α,25-dihydroxyvitamin D3 decreases DNA binding of nuclear factor-κB in human fibroblasts

1 alpha,25-Dihydroxyvitamin D-3 (1,25-(OH)(2)-D-3), the active metabolite of vitamin D, can inhibit NF-kappa B activity in human MRC-5 fibroblasts, targeting DNA binding of NF-kappa B but not translocation of its subunits p50 and p65, The partial inhibition of NF-kappa B DNA binding by 1,25-(OH)(2)-D-3 is dependent on de novo protein synthesis, suggesting that 1,25-(OH)(2)-D-3 may regulate expression of cellular factors which contribute to reduced DNA binding of NF-kappa B. Although NF-kappa B binding is decreased by 1,25-(OH)(2)-D-3 in MRC-5 cells, IL-8 and IL-6 mRNA levels are only moderately downregulated, demonstrating that inhibition of NF-kappa B DNA binding alone is not sufficient for optimal downregulation of these genes. (C) 1998 Federation of European Biochemical Societies.