Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β

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 to...

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Main Authors: Wannit Tongkao-on, Chen Yang, Bianca Y. McCarthy, Warusavithana G. Manori De Silva, Mark S. Rybchyn, Clare Gordon-Thomson, Katie M. Dixon, Gary M. Halliday, Vivienne E. Reeve, Rebecca S. Mason
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/4/1962
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author Wannit Tongkao-on
Chen Yang
Bianca Y. McCarthy
Warusavithana G. Manori De Silva
Mark S. Rybchyn
Clare Gordon-Thomson
Katie M. Dixon
Gary M. Halliday
Vivienne E. Reeve
Rebecca S. Mason
author_facet Wannit Tongkao-on
Chen Yang
Bianca Y. McCarthy
Warusavithana G. Manori De Silva
Mark S. Rybchyn
Clare Gordon-Thomson
Katie M. Dixon
Gary M. Halliday
Vivienne E. Reeve
Rebecca S. Mason
author_sort Wannit Tongkao-on
collection DOAJ
description 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.
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spelling doaj.art-80f07869d5304aa3a7919f28e8a4cc8c2023-12-11T17:18:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224196210.3390/ijms22041962Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-βWannit Tongkao-on0Chen Yang1Bianca Y. McCarthy2Warusavithana G. Manori De Silva3Mark S. Rybchyn4Clare Gordon-Thomson5Katie M. Dixon6Gary M. Halliday7Vivienne E. Reeve8Rebecca S. Mason9Department of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaAnatomy and Histology, University of Sydney, Sydney, NSW 2006, AustraliaDermatology, Faculty of Medicine and Health, University of Sydney, Sydney, NSW 2006, AustraliaFaculty of Veterinary Science, University of Sydney, Sydney, NSW 2006, AustraliaDepartment of Physiology, University of Sydney, Sydney, NSW 2006, AustraliaSusceptibility 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.https://www.mdpi.com/1422-0067/22/4/19621α,25-dihydroxyvitaminD3photoprotectionDNA damagecyclobutane pyrimidine dimersedemaphotoimmune suppression
spellingShingle Wannit Tongkao-on
Chen Yang
Bianca Y. McCarthy
Warusavithana G. Manori De Silva
Mark S. Rybchyn
Clare Gordon-Thomson
Katie M. Dixon
Gary M. Halliday
Vivienne E. Reeve
Rebecca S. Mason
Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
International Journal of Molecular Sciences
1α,25-dihydroxyvitaminD3
photoprotection
DNA damage
cyclobutane pyrimidine dimers
edema
photoimmune suppression
title Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
title_full Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
title_fullStr Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
title_full_unstemmed Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
title_short Sex Differences in Photoprotective Responses to 1,25-Dihydroxyvitamin D3 in Mice Are Modulated by the Estrogen Receptor-β
title_sort sex differences in photoprotective responses to 1 25 dihydroxyvitamin d3 in mice are modulated by the estrogen receptor β
topic 1α,25-dihydroxyvitaminD3
photoprotection
DNA damage
cyclobutane pyrimidine dimers
edema
photoimmune suppression
url https://www.mdpi.com/1422-0067/22/4/1962
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