Ultraviolet B suppresses vitamin D receptor gene expression in keratinocytes.
Keratinocytes not only produce vitamin D3 in response to ultraviolet B light (UVB) and convert 25-hydroxyvitamin D3 to 1 alpha, 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 of de novo protein 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.
Courtois
S J
SJ
Department of Dermatology, Katholieke Universiteit Leuven, Louvain, Belgium.
Segaert
S
S
Degreef
H
H
Bouillon
R
R
Garmyn
M
M
D002109:Caffeic Acids / Q000494:pharmacology; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation / Q000528:radiation effects; D005246:Feedback; D005786:Gene Expression Regulation / Q000528:radiation effects; D016259:Genes, myc / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000528:radiation effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D012980:Sodium Salicylate / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002109:Caffeic Acids; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002762:Cholecalciferol; D014108:Tosylphenylalanyl Chloromethyl Ketone; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D012980:Sodium Salicylate