title: Local corticosterone activation by 11β-hydroxysteroid dehydrogenase 1 in keratinocytes: the role in narrow-band UVB-induced dermatitis.
abstract: Keratinocytes are known to synthesize cortisol through activation of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1). To confirm the function of 11β-HSD1 in keratinocytes during inflammation in vivo, we created keratinocyte-specific-11β-HSD1 knockout mice (K5-Hsd11b1-KO mice) and analyzed the response to narrow-band ultraviolet B (NB-UVB) irradiation. Firstly, we measured the mRNA and protein levels of 11β-HSD1 following NB-UVB irradiation and found that the expression of 11β-HSD1 in keratinocytes of mouse ear skin was enhanced at 3 and 24 hours after 250 mJ/cm(2), 500 mJ/cm(2), 1 J/cm(2), and 2 J/cm(2) NB-UVB irradiation. Next, we determined that 24 hours after exposure to 1 J/cm(2) NB-UVB irradiation, the numbers of F4/80-, CD45-, and Gr-1-positive cells were increased in K5-Hsd11b1-KO mice compared to wild type (WT) mice. Furthermore, the expression of the chemokine (C-X-C-motif) ligand 1 (CXCL1) and interleukin (IL)-6 was also significantly enhanced in NB-UVB-irradiated K5-Hsd11b1-KO mice compared with WT mice. In addition, activation of nuclear factor-kappa B (NF-κB) after NB-UVB irradiation was enhanced in K5-Hsd11b1-KO mice compared to that in WT mice. Thus, NB-UVB-induced inflammation is augmented in K5-Hsd11b1-KO mice compared with WT mice. These results indicate that 11β-HSD1 may suppress NB-UVB-induced inflammation via inhibition of NF-κB activation.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University , Suita, Osaka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Itoi-Ochi
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University , Suita, Osaka, Japan.
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: 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
keywords: 11β-hydroxysteroid dehydrogenase 1; corticosterone; inflammation; keratinocytes; narrow-band UVB