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

1α,25-dihydroxyvitamin D3 decreases DNA binding of nuclear factor-κB in human fibroblasts
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DOI:
10.1016/s0014-5793(98)01153-3
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发表时间:
1998-10-09
期刊:
影响因子:
3.5
通讯作者:
Lindley, IJD
Lindley, IJD
中科院分区:
生物学3区
文献类型:
--
作者:
Harant, H;Wolff, B;Lindley, IJD

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维生素D的活性代谢产物1α,25-二羟基维生素D-3(1,25-(OH)(2)-D-3)可抑制人MRC-5成纤维细胞中核因子-kappaB的活性,靶向与核因子-kappa B的DNA结合,但不能抑制其亚基p50和p65的转位,1,25-(OH)(2)-D-3对核因子-kappa B DNA结合的部分抑制依赖于从头蛋白的合成。提示1,25-(OH)(2)-D-3可能调节导致核因子-kappa B DNA结合减少的细胞因子的表达。虽然在MRC-5细胞中,核因子-kappa B的结合减少了1,25-(OH)(2)-D-3,但IL-8和IL-6的mRNA水平仅有适度下调,表明仅抑制核因子-kappa B DNA结合不足以实现这些基因的最佳下调。(C)1998年欧洲生化学会联合会。
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.