Tongkao-On Wannit, Carter Sally, Reeve Vivienne E, Dixon Katie M, Gordon-Thomson Clare, Halliday Gary M, Tuckey Robert C, Mason Rebecca S
School of Medical Sciences and the Bosch Institute, University of Sydney, NSW, Australia.
Faculty of Veterinary Science, University of Sydney, NSW, Australia.
J Steroid Biochem Mol Biol. 2015 Apr;148:72-8. doi: 10.1016/j.jsbmb.2014.11.015. Epub 2014 Nov 15.
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 46pmol/cm(2) 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 24h 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'.
局部应用1,25 - 二羟基维生素D（1,25D）及其他维生素D化合物已被证明可在一个需要维生素D受体的过程中保护皮肤免受紫外线辐射（UVR）损伤。然而，虽然不表达维生素D受体的小鼠更容易发生光致癌作用，但无法将25 - 羟基维生素D 1α - 羟化形成1,25D的小鼠对UVR诱导的皮肤肿瘤并未表现出易感性增加。一种可能的解释是，一条不涉及1α - 羟化的替代途径可能从维生素D产生光保护化合物。胆固醇侧链裂解酶CYP11A1在皮肤中表达，并产生20 - 羟基维生素D3（20OHD）作为维生素D3的主要产物。我们研究了局部应用20OHD是否会影响UVR诱导的Skh:hr1小鼠的DNA损伤、炎性水肿或免疫抑制。20OHD以23或46pmol/cm²的剂量对小鼠UVR照射后的环丁烷嘧啶二聚体（DNA损伤）具有高度有效的光保护作用，高达98±0.8%，（p<0.001），与1,25D相当。以UVR照射后24小时的皮肤褶厚度测量的晒伤水肿也被20OHD显著降低（p<0.001）。在对UVR抑制的接触性超敏反应（CHS）的研究中，局部应用20OHD对小鼠可防止UVR诱导免疫抑制（p<０.05），类似于相似剂量的1,25D的作用（20OHD的保护率为46±0.6%，1,25D为44±0.5%）。UVR诱导的DNA损伤和免疫抑制均导致对UVR诱导的皮肤肿瘤易感性增加。本研究表明天然存在的维生素D代谢产物20OHD具有潜在的抗光致癌作用，其产生不依赖于1α - 羟化。本文是名为“第17届维生素D研讨会”的特刊的一部分。
