title: Interferon-γ decreases ceramides with long-chain fatty acids: possible involvement in atopic dermatitis and psoriasis.
abstract: Ceramide (CER) with long-chain fatty acids (FAs) in the human stratum corneum (SC) is important for the skin barrier functions. Changes in the CER profile have been associated with abnormal permeability of dermatoses such as atopic dermatitis (AD) and psoriasis. In addition, interferon-γ (IFN-γ) has been known to be abundant in both AD and psoriatic skin lesions. In this study, we aimed to identify the mechanism underlying the alteration of FA chain length of CERs in these diseases. Mass spectrometry analysis of CERs in the SC showed that the proportion of CERs with long-chain FAs was significantly lower in AD and psoriasis patients than in healthy controls, and this reduction was more pronounced in psoriasis than in AD. Using cultured human keratinocytes and epidermal sheets, we found that only IFN-γ among various cytokines decreased the mRNA expression of elongase of long-chain fatty acids (ELOVL) and ceramide synthase (CerS), enzymes involved in FA chain elongation. Furthermore, quantitative analysis showed that IFN-γ decreased the levels of CERs with long-chain FAs. These results suggest that IFN-γ decreases CERs with long-chain FAs through the downregulation of ELOVL and CerS and that this mechanism may be involved in the CER profile alteration observed in psoriasis and AD.
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: tasadachisato@yahoo.co.jp.
authors.forename: Chisato
authors.initials: C
authors.lastname: Tawada
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanoh
authors.affiliation: Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizutani
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Fujisawa
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.affiliation: Department of Dermatology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Seishima
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D002518:Ceramides / Q000276:immunology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology / Q000378:metabolism; D005227:Fatty Acids / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D002518:Ceramides; D005227:Fatty Acids; D007371:Interferon-gamma