UVB induces epidermal 11?-hydroxysteroid dehydrogenase type 1 activity in vivo.

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 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) generates the active GC cortisol from cortisone (or corticosterone from 11-dehydrocorticosterone in rodents). 11?-HSD1 oxo-reductase activity requires the cofactor NADPH, generated by hexose-6-phosphate dehydrogenase. We previously demonstrated increased 11?-HSD1 levels in skin obtained from photoexposed versus photoprotected anatomical regions. However, the direct effect of UVR on 11?-HSD1 expression remains to be elucidated. To investigate the cutaneous regulation of 11?-HSD1 following UVR in vivo, the dorsal skin of female SKH1 mice was irradiated with 50, 100, 200 and 400 mJ/cm(2) UVB. Measurement of transepidermal water loss, 11?-HSD1 activity, mRNA/protein expression and histological studies was taken at 1, 3 and 7 days postexposure. 11?-HSD1 and hexose-6-phosphate dehydrogenase mRNA expression peaked 1 day postexposure to 400 mJ/cm(2) UVB before subsequently declining (days 3 and 7). Corresponding increases in 11?-HSD1 protein and enzyme activity were observed 3 days postexposure coinciding with reduced GC receptor mRNA expression. Immunofluorescence studies revealed 11?-HSD1 localization to hyperproliferative epidermal keratinocytes in UVB-exposed skin. 11?-HSD1 expression and activity were also induced by 200 and 100 (but not 50) mJ/cm(2) UVB and correlated with increased transepidermal water loss (indicative of barrier disruption). UVB-induced 11?-HSD1 activation represents a novel mechanism that may contribute to the regulation of cutaneous responses to UVR exposure.

SUBMITTER: Tiganescu A 

PROVIDER: S-EPMC6365099 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature