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Role of 11β-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis

Authors
 Noo Ri Lee  ;  Beom Jun Kim  ;  Chung Hyeok Lee  ;  Young Bin Lee  ;  Solam Lee  ;  Hyun Jee Hwang  ;  Eunjung Kim  ;  Sung Hee Kim  ;  Min-Geol Lee  ;  Sang Eun Lee  ;  Gareth G Lavery  ;  Eung Ho Choi 
Citation
 SCIENTIFIC REPORTS, Vol.10(1) : 20237, 2020-11 
Journal Title
SCIENTIFIC REPORTS
Issue Date
2020-11
MeSH
11-beta-Hydroxysteroid Dehydrogenase Type 1 / genetics ; 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism* ; Animals ; Case-Control Studies ; Cell Line ; Cytokines / metabolism ; Dermatitis, Atopic / chemically induced ; Dermatitis, Atopic / metabolism* ; Disease Models, Animal ; Epidermis / metabolism ; Epidermis / pathology ; Female ; Gene Knockout Techniques ; Humans ; Keratinocytes / cytology ; Keratinocytes / metabolism ; Mice ; Oxazolone / adverse effects* ; Thymus Gland / metabolism ; Up-Regulation*
Abstract
Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic-pituitary-adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), including the skin. The inactive GC cortisone is converted by 11β-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11β-HSD1 in inflammation is unclear. We assessed whether 11β-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11β-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11β-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11β-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11β-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11β-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.
Files in This Item:
T202006097.pdf Download
DOI
10.1038/s41598-020-77281-x
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Geol(이민걸) ORCID logo https://orcid.org/0000-0001-7040-5335
Lee, Sang Eun(이상은) ORCID logo https://orcid.org/0000-0003-4720-9955
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182534
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