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ABSTRACT: Background
IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood.Methods
We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4.Results
IL-4 induced the upregulation of IL-33 expression in NHEKs. Based on the findings 1) that ovo-like 1 (OVOL1), a susceptible gene of AD, upregulates filaggrin (FLG) and loricrin (LOR) expression in NHEKs and 2) that reduced expression of FLG and LOR leads to production of IL-1 superfamily cytokines, we examined the involvement of OVOL1 in IL-33 expression in NHEKs. Knockdown of OVOL1 induced upregulation of IL-33 expression. Moreover, because Glyteer, an activator of aryl hydrocarbon receptor (AHR), reportedly upregulates OVOL1 expression, we examined whether treatment with Glyteer inhibited IL-33 expression in NHEKs. Treatment with Glyteer inhibited IL-4-induced upregulation of IL-33 expression, which was canceled by knockdown of either AHR or OVOL1.Conclusions
Activation of the AHR-OVOL1 axis inhibits IL-4-induced IL-33 expression, which could be beneficial for the treatment of AD.
SUBMITTER: Tsuji G
PROVIDER: S-EPMC7141508 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Tsuji Gaku G Hashimoto-Hachiya Akiko A Yen Vu Hai VH Miake Sho S Takemura Masaki M Mitamura Yasutaka Y Ito Takamichi T Murata Maho M Furue Masutaka M Nakahara Takeshi T
Journal of clinical medicine 20200324 3
<h4>Background</h4>IL-33, one of the IL-1 superfamily cytokines, has been shown to be associated with pruritus and inflammation in atopic dermatitis (AD). Furthermore, IL-33 production derived from keratinocytes reportedly has a crucial role in the development of AD; however, the mechanism of IL-33 expression has not been fully understood.<h4>Methods</h4>We analyzed IL-33 expression in normal human epidermal keratinocytes (NHEKs) treated with IL-4.<h4>Results</h4>IL-4 induced the upregulation of ...[more]