Aryl hydrocarbon receptor activation downregulates IL-33 expression in keratinocytes via ovo-like 1

Gaku Tsuji, Akiko Hashimoto-Hachiya, Vu Hai Yen, Sho Miake, Masaki Takemura, Yasutaka Mitamura, Takamichi Ito, Maho Murata, Masutaka Furue, Takeshi Nakahara

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10 Citations (Scopus)

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.

Original languageEnglish
Article number891
JournalJournal of Clinical Medicine
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 2020

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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