1. Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β.
- Author
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Tongkao-On W, Yang C, McCarthy BY, De Silva WGM, Rybchyn MS, Gordon-Thomson C, Dixon KM, Halliday GM, Reeve VE, and Mason RS
- Subjects
- Administration, Cutaneous, Animals, Dermatitis, Contact drug therapy, Disease Models, Animal, Estrogen Receptor beta genetics, Female, Immune Tolerance drug effects, Immune Tolerance radiation effects, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Pyrimidine Dimers metabolism, Pyrimidine Dimers radiation effects, Sex Factors, Skin drug effects, Skin metabolism, Skin pathology, Skin radiation effects, Skin Neoplasms prevention & control, Sunburn prevention & control, Calcitriol administration & dosage, Estrogen Receptor beta metabolism, Signal Transduction radiation effects, Sunburn drug therapy, Sunburn metabolism, Sunscreening Agents administration & dosage, Ultraviolet Rays
- Abstract
Susceptibility to photoimmune suppression and photocarcinogenesis is greater in male than in female humans and mice and is exacerbated in female estrogen receptor-beta knockout (ER-β-/-) mice. We previously reported that the active vitamin D hormone, 1,25-dihydroxyvitamin D3 (1,25(OH)2D), applied topically protects against the ultraviolet radiation (UV) induction of cutaneous cyclobutane pyrimidine dimers (CPDs) and the suppression of contact hypersensitivity (CHS) in female mice. Here, we compare these responses in female versus male Skh:hr1 mice, in ER-β-/-/-- versus wild-type C57BL/6 mice, and in female ER-blockaded Skh:hr1 mice. The induction of CPDs was significantly greater in male than female Skh:hr1 mice and was more effectively reduced by 1,25(OH)2D in female Skh:hr1 and C57BL/6 mice than in male Skh:hr1 or ER-β-/- mice, respectively. This correlated with the reduced sunburn inflammation due to 1,25(OH)2D in female but not male Skh:hr1 mice. Furthermore, although 1,25(OH)2D alone dose-dependently suppressed basal CHS responses in male Skh:hr1 and ER-β-/- mice, UV-induced immunosuppression was universally observed. In female Skh:hr1 and C57BL/6 mice, the immunosuppression was decreased by 1,25(OH)2D dose-dependently, but not in male Skh:hr1, ER-β-/-, or ER-blockaded mice. These results reveal a sex bias in genetic, inflammatory, and immune photoprotection by 1,25(OH)2D favoring female mice that is dependent on the presence of ER-β.
- Published
- 2021
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