1α,25‐Dihydroxyvitamin D3 decreases DNA binding of nuclear factor‐κB in human fibroblasts

Abstract

1α,25-Dihydroxyvitamin D₃ (1,25-(OH)₂-D₃), the active metabolite of vitamin D, can inhibit NF-κB activity in human MRC-5 fibroblasts, targeting DNA binding of NF-κB but not translocation of its subunits p50 and p65. The partial inhibition of NF-κB DNA binding by 1,25-(OH)₂-D₃ is dependent on de novo protein synthesis, suggesting that 1,25-(OH)₂-D₃ may regulate expression of cellular factors which contribute to reduced DNA binding of NF-κB. Although NF-κB binding is decreased by 1,25-(OH)₂-D₃ in MRC-5 cells, IL-8 and IL-6 mRNA levels are only moderately downregulated, demonstrating that inhibition of NF-κB DNA binding alone is not sufficient for optimal downregulation of these genes.