Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin |
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Authors: | Beom Jun Kim Noo Ri Lee Chung Hyeok Lee Young Bin Lee Sung Jay Choe Solam Lee Hyun Jee Hwang Eunjung Kim Gareth G Lavery Kyong-Oh Shin Kyungho Park Eung Ho Choi |
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Affiliation: | 1.Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, Korea; (B.J.K.); (N.R.L.); (C.H.L.); (Y.B.L.); (S.J.C.); (S.L.); (H.J.H.); (E.K.);2.Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK;3.Department of Food Science and Nutrition, Convergence Program of Materials Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, Korea; (K.-O.S.); (K.P.) |
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Abstract: | Inactive cortisone is converted into active cortisol by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11β-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11β-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11β-HSD1 knockout mice (n = 11), 11β-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11β-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11β-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier. |
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Keywords: | barrier function skin aging 11-beta-hydroxysteroid dehydrogenase type 1 glucocorticoids epidermal lipids |
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