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

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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.