IL-24 negatively regulates keratinocyte differentiation induced by tapinarof, an aryl hydrocarbon receptor modulator: Implication in the treatment of atopic dermatitis

Yen Hai Vu, Akiko Hashimoto-Hachiya, Masaki Takemura, Ayako Yumine, Yasutaka Mitamura, Takeshi Nakahara, Masutaka Furue, Gaku Tsuji

研究成果: ジャーナルへの寄稿学術誌査読

15 被引用数 (Scopus)

抄録

Skin barrier dysfunction, including reduced filaggrin (FLG) and loricrin (LOR) expression, plays a critical role in atopic dermatitis (AD) development. Since aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, mediates keratinocyte differentiation, it is a potential target for AD treatment. Recently, clinical studies have shown that tapinarof, an AHR modulator, attenuated the development of AD. To examine the molecular mechanism involved in this, we analyzed tapinarof-treated normal human epidermal keratinocytes (NHEKs). Tapinarof upregulated FLG and LOR mRNA and protein expression in an AHR-dependent manner. Tapinarof also induced the secretion of IL-24, a cytokine that activates Janus kinase (JAK)-signal transducer and activator of transcription (STAT), leading to the downregulation of FLG and LOR expression. Knockdown of either IL-24 or STAT3 expression by small interfering RNA (siRNA) transfection augmented the upregulation of FLG and LOR expression induced by tapinarof, suggesting that inhibition of the IL-24/STAT3 axis during AHR activation supports the improvement of skin barrier dysfunction. Furthermore, tapinarof alone could restore the downregulation of FLG and LOR expression induced by IL-4, a key cytokine of AD, and its combination with JAK inhibitors enhanced this effect. These findings provide a new strategy for treating AD using AHR modulators and JAK inhibitors.

本文言語英語
論文番号9412
ページ(範囲)1-16
ページ数16
ジャーナルInternational journal of molecular sciences
21
24
DOI
出版ステータス出版済み - 12月 2 2020

!!!All Science Journal Classification (ASJC) codes

  • 触媒
  • 分子生物学
  • 分光学
  • コンピュータ サイエンスの応用
  • 物理化学および理論化学
  • 有機化学
  • 無機化学

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