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J Immunol Res ; 2019: 3030268, 2019.
Article in English | MEDLINE | ID: mdl-30838224

ABSTRACT

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.


Subject(s)
Ceramides/analysis , Dermatitis, Atopic/immunology , Interferon-gamma/immunology , Skin/immunology , Acetyltransferases/genetics , Animals , Cells, Cultured , Cytokines/genetics , Cytokines/immunology , Dermatitis, Atopic/chemically induced , Disease Models, Animal , Eye Proteins/genetics , Fatty Acid Elongases , Fatty Acids/analysis , Female , Imiquimod , Interferon-gamma/genetics , Membrane Proteins/genetics , Mice , Mice, Inbred BALB C , Psoriasis/chemically induced , Psoriasis/immunology , Skin/pathology , Sphingosine N-Acyltransferase/genetics
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