Tiganescu, A orcid.org/0000-0003-3688-2204, Hupe, M, Jiang, YJ et al. (6 more authors) (2015) UVB induces epidermal 11β-hydroxysteroid dehydrogenase type 1 activity in vivo. Experimental Dermatology, 24 (5). pp. 370-376. ISSN 0906-6705
Abstract
Detrimental consequences of ultraviolet radiation (UVR) in skin include photoageing, immunosuppression and photocarcinogenesis, processes also significantly regulated by local glucocorticoid (GC) availability. In man, the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) generates the active GC cortisol from cortisone (or corticosterone from 11-dehydrocorticosterone in rodents). 11β-HSD1 oxo-reductase activity requires the cofactor NADPH, generated by hexose-6-phosphate dehydrogenase. We previously demonstrated increased 11β-HSD1 levels in skin obtained from photoexposed versus photoprotected anatomical regions. However, the direct effect of UVR on 11β-HSD1 expression remains to be elucidated. To investigate the cutaneous regulation of 11β-HSD1 following UVR in vivo, the dorsal skin of female SKH1 mice was irradiated with 50, 100, 200 and 400 mJ/cm2 UVB. Measurement of transepidermal water loss, 11β-HSD1 activity, mRNA/protein expression and histological studies was taken at 1, 3 and 7 days postexposure. 11β-HSD1 and hexose-6-phosphate dehydrogenase mRNA expression peaked 1 day postexposure to 400 mJ/cm2 UVB before subsequently declining (days 3 and 7). Corresponding increases in 11β-HSD1 protein and enzyme activity were observed 3 days postexposure coinciding with reduced GC receptor mRNA expression. Immunofluorescence studies revealed 11β-HSD1 localization to hyperproliferative epidermal keratinocytes in UVB-exposed skin. 11β-HSD1 expression and activity were also induced by 200 and 100 (but not 50) mJ/cm2 UVB and correlated with increased transepidermal water loss (indicative of barrier disruption). UVB-induced 11β-HSD1 activation represents a novel mechanism that may contribute to the regulation of cutaneous responses to UVR exposure.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | 11β-hydroxysteroid dehydrogenase type 1, glucocorticoid, skin, transepidermal water loss, UVB |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Jan 2023 16:40 |
Last Modified: | 10 Jan 2023 16:40 |
Published Version: | http://dx.doi.org/10.1111/exd.12682 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/exd.12682 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:183382 |