Limits...
Local corticosterone activation by 11β-hydroxysteroid dehydrogenase 1 in keratinocytes: the role in narrow-band UVB-induced dermatitis.

Itoi-Ochi S, Terao M, Murota H, Katayama I - Dermatoendocrinol (2016)

Bottom Line: Keratinocytes are known to synthesize cortisol through activation of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1).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.These results indicate that 11β-HSD1 may suppress NB-UVB-induced inflammation via inhibition of NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University , Suita, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

NB-UVB-induced infiltration of inflammatory cells was increased in the K5-Hsd11b1-KO mouse skin. (A) H&E staining (upper panel) and immunofluorescence staining of F4/80, CD45, and Gr-1 (red) and nuclei (Hoechst 33342, blue) (lower panel) in the 2-month-old WT and K5-Hsd11b1-KO mouse skin 24 hours after NB-UVB irradiation at 1 J/cm2 (N = 8 per group). Rat IgG was used as isotype control. Bar = 100 μm. (B-D) Numbers of F4/80- (B), CD45- (C), Gr-1-positive (D) cells per each high power field in the 2-month-old WT (white bar) and K5-Hsd11b1-KO (black bar) mouse skin after NB-UVB irradiation at 1 J/cm2. Three sections from each mouse were evaluated. The bars indicate the mean ± SD (N = 8; **P < 0.01, two-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons). (E) Myeloperoxidase (MPO) activity in skin from 2-month-old mice 24 hours after NB-UVB irradiation at 1 J/cm2. The bars indicate the mean ± SD (N = 6; **P < 0.01, 2-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4862380&req=5

f0002: NB-UVB-induced infiltration of inflammatory cells was increased in the K5-Hsd11b1-KO mouse skin. (A) H&E staining (upper panel) and immunofluorescence staining of F4/80, CD45, and Gr-1 (red) and nuclei (Hoechst 33342, blue) (lower panel) in the 2-month-old WT and K5-Hsd11b1-KO mouse skin 24 hours after NB-UVB irradiation at 1 J/cm2 (N = 8 per group). Rat IgG was used as isotype control. Bar = 100 μm. (B-D) Numbers of F4/80- (B), CD45- (C), Gr-1-positive (D) cells per each high power field in the 2-month-old WT (white bar) and K5-Hsd11b1-KO (black bar) mouse skin after NB-UVB irradiation at 1 J/cm2. Three sections from each mouse were evaluated. The bars indicate the mean ± SD (N = 8; **P < 0.01, two-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons). (E) Myeloperoxidase (MPO) activity in skin from 2-month-old mice 24 hours after NB-UVB irradiation at 1 J/cm2. The bars indicate the mean ± SD (N = 6; **P < 0.01, 2-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons).

Mentions: Following NB-UVB irradiation of WT and K5-Hsd11b1-KO mice, the function of increased 11β-HSD1 in keratinocytes was evaluated. NB-UVB irradiation significantly increased the number of infiltrated inflammatory cells in the dermis (Fig. 2A). Specifically, the numbers of F4/80-, CD45-, and Gr-1-positive cells were significantly higher in irradiated K5-Hsd11b1-KO mice than in irradiated WT mice (Fig. 2A-D). Accordingly, myeloperoxidase (MPO) activity was significantly increased in the NB-UVB-irradiated K5-Hsd11b1-KO mice compared to that in the irradiated WT mice (Fig. 2E).Figure 2.


Local corticosterone activation by 11β-hydroxysteroid dehydrogenase 1 in keratinocytes: the role in narrow-band UVB-induced dermatitis.

Itoi-Ochi S, Terao M, Murota H, Katayama I - Dermatoendocrinol (2016)

NB-UVB-induced infiltration of inflammatory cells was increased in the K5-Hsd11b1-KO mouse skin. (A) H&E staining (upper panel) and immunofluorescence staining of F4/80, CD45, and Gr-1 (red) and nuclei (Hoechst 33342, blue) (lower panel) in the 2-month-old WT and K5-Hsd11b1-KO mouse skin 24 hours after NB-UVB irradiation at 1 J/cm2 (N = 8 per group). Rat IgG was used as isotype control. Bar = 100 μm. (B-D) Numbers of F4/80- (B), CD45- (C), Gr-1-positive (D) cells per each high power field in the 2-month-old WT (white bar) and K5-Hsd11b1-KO (black bar) mouse skin after NB-UVB irradiation at 1 J/cm2. Three sections from each mouse were evaluated. The bars indicate the mean ± SD (N = 8; **P < 0.01, two-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons). (E) Myeloperoxidase (MPO) activity in skin from 2-month-old mice 24 hours after NB-UVB irradiation at 1 J/cm2. The bars indicate the mean ± SD (N = 6; **P < 0.01, 2-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4862380&req=5

f0002: NB-UVB-induced infiltration of inflammatory cells was increased in the K5-Hsd11b1-KO mouse skin. (A) H&E staining (upper panel) and immunofluorescence staining of F4/80, CD45, and Gr-1 (red) and nuclei (Hoechst 33342, blue) (lower panel) in the 2-month-old WT and K5-Hsd11b1-KO mouse skin 24 hours after NB-UVB irradiation at 1 J/cm2 (N = 8 per group). Rat IgG was used as isotype control. Bar = 100 μm. (B-D) Numbers of F4/80- (B), CD45- (C), Gr-1-positive (D) cells per each high power field in the 2-month-old WT (white bar) and K5-Hsd11b1-KO (black bar) mouse skin after NB-UVB irradiation at 1 J/cm2. Three sections from each mouse were evaluated. The bars indicate the mean ± SD (N = 8; **P < 0.01, two-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons). (E) Myeloperoxidase (MPO) activity in skin from 2-month-old mice 24 hours after NB-UVB irradiation at 1 J/cm2. The bars indicate the mean ± SD (N = 6; **P < 0.01, 2-way ANOVA followed by the Bonferroni-Dunn test for multiple comparisons).
Mentions: Following NB-UVB irradiation of WT and K5-Hsd11b1-KO mice, the function of increased 11β-HSD1 in keratinocytes was evaluated. NB-UVB irradiation significantly increased the number of infiltrated inflammatory cells in the dermis (Fig. 2A). Specifically, the numbers of F4/80-, CD45-, and Gr-1-positive cells were significantly higher in irradiated K5-Hsd11b1-KO mice than in irradiated WT mice (Fig. 2A-D). Accordingly, myeloperoxidase (MPO) activity was significantly increased in the NB-UVB-irradiated K5-Hsd11b1-KO mice compared to that in the irradiated WT mice (Fig. 2E).Figure 2.

Bottom Line: Keratinocytes are known to synthesize cortisol through activation of the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1).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.These results indicate that 11β-HSD1 may suppress NB-UVB-induced inflammation via inhibition of NF-κB activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Graduate School of Medicine, Osaka University , Suita, Osaka, Japan.

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.

No MeSH data available.


Related in: MedlinePlus