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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/cm2, 500 mJ/cm2, 1 J/cm2, and 2 J/cm2 NB-UVB irradiation. Next, we determined that 24 hours after exposure to 1 J/cm2 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.
Abbreviations
| 11β-HSD1 | = | 11β-hydroxysteroid dehydrogenase 1 |
| cDNA | = | complementary DNA |
| CXCL1 | = | chemokine (C-X-C-motif) ligand1 |
| ELISA | = | enzyme-linked immunosorbent assay |
| GAPDH | = | glyceraldehyde-3-phosphate dehydrogenase |
| GC | = | glucocorticoid |
| HPA | = | hypothalamo-pituitary-adrenal |
| IL-6 | = | interleukin-6 |
| K5-Hsd11b1-KO | = | keratinocyte-specific 11β-HSD1 knockout |
| MPO | = | myeloperoxidase |
| NB-UVB | = | narrow-band UVB |
| NF-κB | = | nuclear factor-kappa B |
| PBS | = | phosphate-buffered saline |
| SD | = | standard deviation |
| TBS | = | Tris-buffered saline |
| WT | = | wildtype |
Disclosure of potential conflics of interest
No potential conflicts of interest were disclosed.
Acknowledgments
The authors thank Mr. Kenju Nishida, Ms. Sayaka Matsumura, Ms. Eriko Nobuyoshi, and Ms. Yumiko Fujii for research assistance.
Funding
This work was supported in part by a Grant-in-Aid for Research Activity Start-up (No. 15H06375) and the LYDIA O'LEARY Memorial Foundation.