cholecalciferol and caffeic-acid-phenethyl-ester

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.

Topics: Caffeic Acids; Cells, Cultured; Cholecalciferol; Dose-Response Relationship, Radiation; Down-Regulation; Feedback; Gene Expression Regulation; Genes, myc; Humans; Keratinocytes; Phenylethyl Alcohol; Receptors, Calcitriol; RNA, Messenger; Signal Transduction; Sodium Salicylate; Tosylphenylalanyl Chloromethyl Ketone; Ultraviolet Rays