673 11β-hydroxysteroid dehydrogenase type 1 activation induced by UVB might be a possible mechanism of skin barrier dysfunction due to UV exposure

Abstract

Ultraviolet light (UV) radiation to the skin causes dose- and wavelength- dependent reactions, including skin barrier dysfunction. Long-term exposure to even low dose UV induces the alteration of skin barrier presenting prominent ceramide decrease in the stratum corneum (SC) intercellular lipids. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which converts inactive cortisone to active cortisol in peripheral tissues and inhibits keratinocytes and fibroblasts proliferation, is known to be induced by UVB. We performed in vitro, in vivo, ex-vivo studies to elucidate whether skin barrier dysfunction induced by UV could be resulted from 11β-HSD1 activation after UV irradiation. We observed that 11β-HSD1 expression was increased by cortisol treatment itself and UV irradiation, thereby rapidly converting cortisone into cortisol. UVB irradiation increases 11β-HSD1 expression as well as inflammatory cytokines using HSD11B1 siRNA transfected normal human epidermal keratinocytes. 11β-HSD1 mRNA was prominently higher in UVB irradiated primary human keratinocytes compared with control. Keratinocytes transfected with HSD11B1 siRNA decreased the expression of 11β-HSD1 mRNA and did not increase cortisol even when the keratinocytes were irradiated by UVB. In vitro, increased cortisol converted by 11β-HSD1 inhibits keratinocyte differentiation. Cortisone decreased the mRNA and protein expression of keratinocyte differentiation markers in UVB-exposed keratinocytes. 11β-HSD1 expression remarkably increased in UV exposed skin and intrinsic aged skin. Skin barrier function presented by transpidermal water loss, SC hydration and SC integrity was impaired in long term UV exposed skin and intrinsic aged skin. Therefore, 11β-HSD1 activation by UVB might suggest another possible mechanism on skin barrier dysfunction due to UV exposure.