CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds

W. Tongkao-On, S.E. Carter, V.E. Reeve, K.M. Dixon, C. Gordon-Thomson, G.M. Halliday, Robert Tuckey, R.S. Mason

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

© 2014 Published by Elsevier Ltd. All rights reserved. Topical 1,25-dihydroxyvitamin D (1,25D) and other vitamin D compounds have been shown to protect skin from damage by ultraviolet radiation (UVR) in a process that requires the vitamin D receptor. Yet, while mice which do not express the vitamin D receptor are more susceptible to photocarcinogenesis, mice unable to 1α-hydroxylate 25-hydroxyvitamin D to form 1,25D do not show increased susceptibility to UVR-induced skin tumors. A possible explanation is that an alternative pathway, which does not involve 1α-hydroxylation, may produce photoprotective compounds from vitamin D. The cholesterol side chain cleavage enzyme CYP11A1 is expressed in skin and produces 20-hydroxyvitamin D3 (20OHD) as a major product of vitamin D3. We examined whether topical 20OHD would affect UVR-induced DNA damage, inflammatory edema or immune suppression produced in Skh:hr1 mice. Photoprotection by 20OHD at 23 or 46 pmol/cm2 against cyclobutane pyrimidine dimers (DNA lesions) after UVR in mice was highly effective, up to 98 ± 0.8%, (p <0.001) and comparable to that of 1,25D. Sunburn edema measured as skinfold thickness 24 h after UVR was also significantly reduced by 20OHD (p <0.001). In studies of contact hypersensitivity (CHS), which is suppressed by UVR, topical application of 20OHD to mice protected against UVR-induced immunosuppression (p <0.05), similar to the effect of 1,25D at similar doses (46 ± 0.6% protection with 20OHD, 44 ± 0.5% with 1,25D). Both UVR-induced DNA damage and immunosuppression contribute to increased susceptibility to UVR-induced skin tumors. This study indicates a potentially anti-photocarcinogenic role of the naturally occurring vitamin D metabolite, 20OHD, which does not depend on 1α-hydroxylation for generation. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.
Original languageEnglish
Pages (from-to)72-78
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume148
DOIs
Publication statusPublished - Apr 2015

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