Ultraviolet B Suppresses Vitamin D Receptor Gene Expression in Keratinocytes

Keratinocytes not only produce vitamin D3in response to ultraviolet B light (UVB) and convert 25-hydroxyvitamin D3to 1α,25-dihydroxyvitamin D3(1,25(OH)2D) but also possess the vitamin D receptor (VDR) and respond to 1,25(OH)2D. We characterized the regulation of the expression of the VDR gene in pri...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1998-05, Vol.246 (1), p.64-69
Main Authors: Courtois, Stéphane J., Segaert, Siegfried, Degreef, Hugo, Bouillon, Roger, Garmyn, Marjan
Format: Article
Language:English
Subjects:
Caffeic Acids - pharmacology
Cells, Cultured
Cholecalciferol - biosynthesis
Dose-Response Relationship, Radiation
Down-Regulation - radiation effects
Feedback
Gene Expression Regulation - radiation effects
Genes, myc - radiation effects
Humans
Keratinocytes - metabolism
Keratinocytes - radiation effects
Phenylethyl Alcohol - analogs & derivatives
Phenylethyl Alcohol - pharmacology
Receptors, Calcitriol - genetics
Receptors, Calcitriol - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal Transduction
Sodium Salicylate - pharmacology
Tosylphenylalanyl Chloromethyl Ketone - pharmacology
Ultraviolet Rays - adverse effects
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Summary:Keratinocytes not only produce vitamin D3in response to ultraviolet B light (UVB) and convert 25-hydroxyvitamin D3to 1α,25-dihydroxyvitamin D3(1,25(OH)2D) but also possess the vitamin D receptor (VDR) and respond to 1,25(OH)2D. We characterized the regulation of the expression of the VDR gene in primary human keratinocytes following UVB irradiation. We report a marked dose-dependent down-regulation of the VDR mRNA and protein within a few hours after irradiation. This occurs independently ofde novoprotein synthesis and is not due to a change in the half-life of the VDR mRNA. Interestingly, treatment of the cells with sodium salicylate, caffeic acid phenethyl ester and tosylphenylchloromethylketone inhibited this down-regulation. Our results strongly suggest the existence of a feedback mechanism in that UVB initiates vitamin D synthesis in keratinocytes and at the same time limits VDR abundance. They also provide a rational explanation for the reported lack of any additive effect between 1,25(OH)2D and UVB phototherapy in the treatment of psoriasis.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1998.8573