1Alpha,25-dihydroxyvitamin D3 decreases DNA binding of nuclear factor-kappaB in human fibroblasts.
1Alpha,25-dihydroxyvitamin D3 (1,25-(OH)2-D3), the active metabolite of vitamin D, can inhibit NF-kappaB activity in human MRC-5 fibroblasts, targeting DNA binding of NF-kappaB but not translocation of its subunits p50 and p65. The partial inhibition of NF-kappaB 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-kappaB. Although NF-kappaB 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-kappaB DNA binding alone is not sufficient for optimal downregulation of these genes.
Harant
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Department of Cellular and Molecular Biology, Novartis Research Institute, Vienna, Austria. Hanna.Harant@pharma.novartis.com
Wolff
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Lindley
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D001665:Binding Sites; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008168:Lung; D046911:Macromolecular Substances; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D046911:Macromolecular Substances; D016328:NF-kappa B; D012333:RNA, Messenger; D003907:Dexamethasone; D004247:DNA; D002117:Calcitriol