IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model

IFN-γ is detected in chronic lesions of atopic dermatitis (AD); however, its specific role remains to be elucidated. An impaired stratum corneum barrier function is a hallmark of AD, and it is associated with a reduction in ceramides with long-chain fatty acids (FAs) in the stratum corneum. FA elong...

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Main Authors: Hiroyuki Kanoh, Asako Ishitsuka, Etsuko Fujine, Shuhei Matsuhaba, Mitsuhiro Nakamura, Hiroyasu Ito, Naoki Inagaki, Yoshiko Banno, Mariko Seishima
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2019/3030268
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author Hiroyuki Kanoh
Asako Ishitsuka
Etsuko Fujine
Shuhei Matsuhaba
Mitsuhiro Nakamura
Hiroyasu Ito
Naoki Inagaki
Yoshiko Banno
Mariko Seishima
author_facet Hiroyuki Kanoh
Asako Ishitsuka
Etsuko Fujine
Shuhei Matsuhaba
Mitsuhiro Nakamura
Hiroyasu Ito
Naoki Inagaki
Yoshiko Banno
Mariko Seishima
author_sort Hiroyuki Kanoh
collection DOAJ
description IFN-γ is detected in chronic lesions of atopic dermatitis (AD); however, its specific role remains to be elucidated. An impaired stratum corneum barrier function is a hallmark of AD, and it is associated with a reduction in ceramides with long-chain fatty acids (FAs) in the stratum corneum. FA elongases, ELOVL1 and ELOVL4, are essential for the synthesis of these ceramides, together with ceramide synthase 3 (CerS3). We have previously shown that IFN-γ, but not other cytokines, induced the downregulation of these enzymes in cultured keratinocytes. Our aim was to investigate the in vivo role of IFN-γ in the lesional skin of AD by analyzing mouse dermatitis models. The local mRNA expression of IFN-γ increased in mite fecal antigen-induced AD-like dermatitis in NC/Nga mice but not in imiquimod-induced psoriasis-like dermatitis in BALB/c mice. The mRNA expression of ELOVL1 and ELOVL4 significantly decreased in AD-like dermatitis, whereas ELOVL1 increased in psoriasis-like dermatitis. The expression of CerS3 increased slightly in AD-like dermatitis, but it increased by 4.6-fold in psoriasis-like dermatitis. Consistently, the relative amount of ceramides with long-chain FAs decreased in AD-like dermatitis but not in psoriasis-like dermatitis. These results suggest that IFN-γ in the lesional skin may reduce ceramides with long-chain FAs by decreasing the expression of ELOVL. Thus, IFN-γ may contribute to the chronicity of AD by impairing barrier function.
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spelling doaj-art-d1e749ab404943d28eaac3b0972670822025-08-20T02:19:43ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/30302683030268IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis ModelHiroyuki Kanoh0Asako Ishitsuka1Etsuko Fujine2Shuhei Matsuhaba3Mitsuhiro Nakamura4Hiroyasu Ito5Naoki Inagaki6Yoshiko Banno7Mariko Seishima8Department of Dermatology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanLaboratory of Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, JapanLaboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, JapanDepartment of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanLaboratory of Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-Nishi, Gifu 501-1196, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanDepartment of Dermatology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, JapanIFN-γ is detected in chronic lesions of atopic dermatitis (AD); however, its specific role remains to be elucidated. An impaired stratum corneum barrier function is a hallmark of AD, and it is associated with a reduction in ceramides with long-chain fatty acids (FAs) in the stratum corneum. FA elongases, ELOVL1 and ELOVL4, are essential for the synthesis of these ceramides, together with ceramide synthase 3 (CerS3). We have previously shown that IFN-γ, but not other cytokines, induced the downregulation of these enzymes in cultured keratinocytes. Our aim was to investigate the in vivo role of IFN-γ in the lesional skin of AD by analyzing mouse dermatitis models. The local mRNA expression of IFN-γ increased in mite fecal antigen-induced AD-like dermatitis in NC/Nga mice but not in imiquimod-induced psoriasis-like dermatitis in BALB/c mice. The mRNA expression of ELOVL1 and ELOVL4 significantly decreased in AD-like dermatitis, whereas ELOVL1 increased in psoriasis-like dermatitis. The expression of CerS3 increased slightly in AD-like dermatitis, but it increased by 4.6-fold in psoriasis-like dermatitis. Consistently, the relative amount of ceramides with long-chain FAs decreased in AD-like dermatitis but not in psoriasis-like dermatitis. These results suggest that IFN-γ in the lesional skin may reduce ceramides with long-chain FAs by decreasing the expression of ELOVL. Thus, IFN-γ may contribute to the chronicity of AD by impairing barrier function.http://dx.doi.org/10.1155/2019/3030268
spellingShingle Hiroyuki Kanoh
Asako Ishitsuka
Etsuko Fujine
Shuhei Matsuhaba
Mitsuhiro Nakamura
Hiroyasu Ito
Naoki Inagaki
Yoshiko Banno
Mariko Seishima
IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
Journal of Immunology Research
title IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
title_full IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
title_fullStr IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
title_full_unstemmed IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
title_short IFN-γ Reduces Epidermal Barrier Function by Affecting Fatty Acid Composition of Ceramide in a Mouse Atopic Dermatitis Model
title_sort ifn γ reduces epidermal barrier function by affecting fatty acid composition of ceramide in a mouse atopic dermatitis model
url http://dx.doi.org/10.1155/2019/3030268
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