213 Increased 11β-hydroxysteroid dehydrogenase type 1 contributes to the impaired barrier in aged skin

Abstract

11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone, an inactive form of glucocorticoid (GC) into cortisol, the active form in human. It is expressed by several tissues including the skin. Excessive active GC deteriorates skin barrier function. Aged skin presents skin barrier impairment. This study was conducted in human and mice to determine if 11β-HSD1 affects the impaired barrier function of aged skin. For human study, elderly and young peoples were enrolled. Mice were divided into the wild aged mice, wild aged mice treated by topical 11β-HSD1 inhibitor, 11β-HSD1 knockout (KO) mice, wild young mice, and wild young mice treated by 11β-HSD1 inhibitor. Cortisol levels were elevated in the stratum corneum (SC) and oral epithelium of the elderly rather than the young. The 11β-HSD1 expression was increased in immunohistochemistry staining of aged mouse skin. Aged mice showed higher transepidermal water loss (TEWL) and lower SC hydration than young ones. Serum inflammatory cytokines such as interleukin-1α, -4, -31 and tumor necrosis factor-α were significantly increased in aged mice than in young mice. SC corticosterone was suppressed in aged 11β-HSD1 KO mice and topical 11β-HSD1 inhibitor applied wild-type mice. Horneodesmosome density was suppressed in aged wild mice, but elevated in aged 11β-HSD1 KO mice and in aged wild mice treated by topical 11β-HSD1 inhibitor. The number of lamellar bodies was increased in topical 11β-HSD1 inhibitor applied mice compared to wild aged mice. The amounts of SC lipids including ceramides, cholesterol, and fatty acids were increased in topical 11β-HSD1 inhibitor applied mice compared to wild aged mice. Expressions of mRNA of lipid synthesis related enzymes were increased in aged 11β-HSD1 KO mice and topical 11β-HSD1 inhibitor applied wild mice. Conclusively, 11β-HSD1 expression is elevated in the aged skin, that increases active GC and then deteriorates skin barrier function.