A 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Inhibitor, 11b-0048, Effectively Suppresses the Expression of 11β-HSD1 Activated in Cultured Keratinocytes and in Diabetic Murine Skin
- Author:
Ju Yeong LEE
1
;
Hyun Jee HWANG
;
Eunjung KIM
;
Jee-Young LEE
;
Seunghyun KANG
;
Eung Ho CHOI
Author Information
- Publication Type:Original Article
- From:Annals of Dermatology 2026;38(3):210-219
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Elevated active glucocorticoids (GCs) are implicated in skin barrier dysfunction, notably in aging and diabetes. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive GCs to active forms, potentially exacerbating this dysfunction.
Objective:We aimed to investigate the impact of a novel 11β-HSD1 inhibitor on skin inflammation using both in vitro and in vivo models.
Methods:To elucidate the efficacy of a new 11β-HSD1 inhibitor in mitigating skin inflammation induced by various triggers, including dexamethasone treatment, ultraviolet B irradiation, and high glucose levels, in cultured human keratinocytes and the db/db mice as a type 2 diabetes murine model. In cultured keratinocytes, we assessed the effects of the 11β-HSD1 inhibitor on cortisol levels, 11β-HSD1 expression, and cytokine production under conditions simulating inflammation. In db/db mice, we evaluated the inhibitor’s impact on skin barrier function, hemoglobin A1c (HbA1c) levels, corticosterone levels, 11β-HSD1 expression, and cytokine profiles following a 2-week treatment regimen.
Results:Our results demonstrated that both the novel 11β-HSD1 inhibitor and a known inhibitor reduced cortisol levels, 11β-HSD1 expression, and inflammatory cytokine production in cultured keratinocytes. In db/db mice, treatment with either inhibitor improved skin barrier function, lowered serum HbA1c levels, and decreased corticosterone, 11β-HSD1, and inflammatory cytokine expression.
Conclusion:A new 11β-HSD1 inhibitor, “11b-0048,” showed a significant inhibitory effect on the expression of 11β-HSD1 in keratinocytes activated by various conditions and diabetic skin.
