UVB-induced production of 1,25-dihydroxyvitamin D3 and vitamin D activity in human keratinocytes pretreated with a sterol Δ7-reductase inhibitor

✍ Scribed by Katleen Vantieghem; Anne-Marie Kissmeyer; Petra De Haes; Roger Bouillon; Siegfried Segaert

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 206 KB
• Volume: 98
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.20756

✦ Synopsis

The skin fulfills an important role in the vitamin D photo-endocrine system. Epidermis is not only the site of vitamin D 3 photoproduction. In addition, epidermal keratinocytes contain the vitamin D receptor (VDR) and possess 25-hydroxylase and 1a-hydroxylase activity indicating that all components of the vitamin D system are present. We investigated whether these components cooperate in inducing vitamin D activity upon treatment with physiological UVB doses. Upon irradiation, 24-hydroxylase mRNA was induced in keratinocytes pretreated with a sterol D 7 -reductase inhibitor (BM15766) whereby the 7-dehydrocholesterol content increased by 300-fold. Transfection experiments with a vitamin D response element containing construct confirmed VDR-dependent gene activation. Furthermore, the UVB-dependent induction of 24-hydroxylase was blocked by the cytochrome-P450 inhibitor ketoconazole. The 24hydroxylase inducing photoproduct was transferable to unirradiated keratinocytes by medium and cellular homogenates of UVB-irradiated, BM15766-pretreated cells and was identified as 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] by highperformance liquid chromatography with tandem mass spectrometric detection. Addition of vitamin D binding protein blunted UVB-induced 24-hydroxylase suggesting the possibility of a paracrine or autocrine role for 1,25(OH) 2 D 3 . In conclusion, epidermal keratinocytes can produce vitamin D 3 , convert it to 1,25(OH) 2 D 3 and respond to it upon UVB irradiation in the absence of exogenous 7-dehydrocholesterol and therefore contain a unique and complete photoendocrine vitamin D system.