title: Local Glucocorticoid Activation by 11β-Hydroxysteroid Dehydrogenase 1 in Keratinocytes: The Role in Hapten-Induced Dermatitis.
abstract: Over the past decade, extra-adrenal cortisol production was reported in various tissues. The enzyme that catalyzes the conversion of hormonally inactive cortisone into active cortisol in cells is 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). We recently reported that 11β-HSD1 is also expressed in keratinocytes and regulates inflammation and keratinocyte proliferation. To investigate the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific 11β-HSD1 knockout (K5-Hsd11b1-KO) mice and analyzed the inflammatory response in models of hapten-induced contact irritant dermatitis. K5-Hsd11b1-KO mice showed enhanced ear swelling in low-dose oxazolone-, 2,4,6-trinitro-1-chlorobenzene (TNCB)-, and 2,4-dinitrofluorobenzene-induced irritant dermatitis associated with increased inflammatory cell infiltration. Topical application of corticosterone dose dependently suppressed TNCB-induced ear swelling and cytokine expression. Similarly in mouse keratinocytes in vitro, corticosterone dose dependently suppressed 2,4,6-trinitrobenzenesulfonic acid-induced IL-1α and IL-1β expression. The effect of 11-dehydrocorticosterone was attenuated in TNCB-induced irritant dermatitis in K5-Hsd11b1-KO mice compared with wild-type mice. In human samples, 11β-HSD1 expression was decreased in epidermis of psoriasis vulgaris compared with healthy skin. Taken together, these data suggest that corticosterone activation by 11β-HSD1 in keratinocytes suppresses hapten-induced irritant dermatitis through suppression of expression of cytokines, such as IL-1α and IL-1β, in keratinocytes.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. Electronic address: mterao@derma.med.osaka-u.ac.jp.
authors.forename: Mika
authors.initials: M
authors.lastname: Terao
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Itoi
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Matsumura
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Lingli
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Murota
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Katayama
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D003877:Dermatitis, Contact / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000378:metabolism*; D006241:Haptens / Q000633:toxicity; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005938:Glucocorticoids; D006241:Haptens; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1