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- W2509225596 abstract "The increase in the prevalence of atopic dermatitis (AD) is reported to be correlated with air pollution levels. Polycyclic aromatic hydrocarbons (PAHs) were identified as the component responsible for the air pollutant-induced inflammation. PAHs exert their biological effects via binding to a transcription factor, aryl hydrocarbon receptor (AhR). We have previously established the transgenic mice whose keratinocytes express the constitutive active form of AhR (AhR-CA mice) and reported AhR-CA mice show barrier dysfunction, Th2-type skin inflammation and alloknesis with epidermal hyperinnervation. However, it remained unknown whether air pollution-induced AhR activation induce AD-like pathologies observed in AhR-CA mice, since AhR has diverse functions depending on the type of ligands. To explorer the effect of chronic AhR activation by AhR ligands, we treated the skin of AhRflox/flox or AhRflox/flox::K5-Cre mice with 7,12-Dimethylbenz[a]anthracene (DMBA), a not-degradable PAHs included in air pollutants, and 6-Formylindolo[3,2-b]carbazole (FICZ), a rapidly metabolized-natural AhR ligand in the skin. The skin of DMBA-applied AhRflox/flox mice exhibited scaling, T cell and mast cell infiltration, upregulated Tslp, Il33 and Il4ra gene expression and elevated serum IgE level. Furthermore, scratching behavior, alloknesis and epidermal hyperinnervation were also observed in DMBA-applied AhRflox/flox mice. In contrast, almost all of these pathologies were not observed in DMBA-applied AhRflox/flox::K5-Cre mice nor FICZ-applied mice. To investigate the mechanism of different effects between DMBA and FICZ, we exposed both ligands to primary human keratinocytes either in differentiated or un-differentiated status induced by different Ca2+ load. AD-associated genes, including TSLP and IL33, were upregulated only when DMBA was exposed to un-differeniated keratinocytes. These results suggest air pollutants penetrate through the skin and activate AhR in keratinocytes at the basal layer, leading to AD-like pathologies." @default.
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- W2509225596 date "2016-09-01" @default.
- W2509225596 modified "2023-10-14" @default.
- W2509225596 title "315 Air pollution activates Aryl hydrocarbon receptor of undifferentiated keratinocytes, leading to atopic dermatitis-like pathologies" @default.
- W2509225596 doi "https://doi.org/10.1016/j.jid.2016.06.335" @default.
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