ArticlePloS one2009
20-Hydroxycholecalciferol, product of vitamin D3 hydroxylation by P450scc, decreases NF-kappaB activity by increasing IkappaB alpha levels in human keratinocytes.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 129 citations in OpenAlex.
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- The vitamin DAmerican journal of physiology. Cell physiology · 2025Article
- The impact of vitamin D3 administration and of high fat diet on oxidative stress and inflammation in experimentally induced polycystic ovary syndrome.Medicine and pharmacy reports · 2024Article
- Biological Effects of CYP11A1-Derived Vitamin D and Lumisterol Metabolites in the Skin.The Journal of investigative dermatology · 2024Review
- Research Progress in Skin Aging and Immunity.International journal of molecular sciences · 2024Review
- Nongenomic Activities of Vitamin D.Nutrients · 2022Review
- Novel CYP11A1-Derived Vitamin D and Lumisterol Biometabolites for the Management of COVID-19.Nutrients · 2022Review
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- Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy.International journal of molecular sciences · 2022Review
- Metabolic activation of tachysterolFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Synthesis of Deuterium-Labeled Vitamin D Metabolites as Internal Standards for LC-MS Analysis.Molecules (Basel, Switzerland) · 2022Article
- Chemical synthesis, biological activities and action on nuclear receptors of 20S(OH)DBioorganic chemistry · 2022Article
- Vitamin D3 and its hydroxyderivatives as promising drugs against COVID-19: a computational study.Journal of biomolecular structure & dynamics · 2022Article
- 1,25-Dihydroxyvitamin D3 and 20-Hydroxyvitamin D3 Upregulate LAIR-1 and Attenuate Collagen Induced Arthritis.International journal of molecular sciences · 2021Article
- The Impact of Vitamin D on Skin Aging.International journal of molecular sciences · 2021Review
- The significance of CYP11A1 expression in skin physiology and pathology.Molecular and cellular endocrinology · 2021Article
- Antifibrogenic Activities of CYP11A1-derived Vitamin D3-hydroxyderivatives Are Dependent on RORγ.Endocrinology · 2021Article
- 20Frontiers in immunology · 2021Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1) to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation of both primary and immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB) plays a pivotal role in the regulation of cell proliferation, differentiation and apoptosis, we examined the capability of 20-hydroxycholecalciferol to modulate the activity of NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol) as a positive control. 20-hydroxycholecalciferol inhibits the activation of NFkappaB DNA binding activity as well as NF-kappaB-driven reporter gene activity in keratinocytes. Also, 20-hydroxycholecalciferol induced significant increases in the mRNA and protein levels of the NF-kappaB inhibitor protein, IkappaB alpha, in a time dependent manner, while no changes in total NF-kappaB-p65 mRNA or protein levels were observed. Another measure of NF-kappaB activity, p65 translocation from the cytoplasm into the nucleus was also inhibited in extracts of 20-hydroxycholecalciferol treated keratinocytes. Increased IkappaB alpha was concomitantly observed in cytosolic extracts of 20-hydroxycholecalciferol treated keratinocytes, as determined by immunoblotting and immunofluorescent staining. In keratinocytes lacking vitamin D receptor (VDR), 20-hydroxycholecalciferol did not affect IkappaB alpha mRNA levels, indicating that it requires VDR for its action on NF-kappaB activity. Comparison of the effects of calcitrol, hormonally active form of vitamin D3, with 20-hydrocholecalciferol show that both agents have a similar potency in inhibiting NF-kappaB. Since NF-kappaB is a major transcription factor for the induction of inflammatory mediators, our findings indicate that 20-hydroxycholecalciferol may be an effective therapeutic agent for inflammatory and hyperproliferative skin diseases.
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