Ultraviolet B suppresses vitamin D receptor gene expression in keratinocytes

Keratinocytes not only produce vitamin DQ in response to ultraviolet B light (UVB) and convert 25-hydroxyvitamin D-3 to 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)(2)D) but also possess the vitamin D receptor (VDR) and respond to 1,25(OH)(2)D. 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. Over 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)(2)D and UVB phototherapy in the treatment of psoriasis. (C) 1998 Academic Press.