Dual oxidase 1 induced by Th2 cytokines promotes STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B in human epidermal keratinocytes

Satoshi Hirakawa, Rumiko Saito, Hiroshi Ohara, Ryuhei Okuyama, Setsuya Aiba

研究成果: Article査読

42 被引用数 (Scopus)

抄録

Although hydrogen peroxide (H2O2) is better known for its cytotoxic effects, in recent years it has been shown to play a crucial role in eukaryotic signal transduction. In respiratory tract epithelial cells, the dual oxidase (DUOX) proteins 1 and 2 has been identified as the cellular source of H2O2. However, the expression of DUOX1 or DUOX2 has not yet been examined in keratinocytes. In this study, using a DNA microarray, we demonstrated that, of the seven NOX/DUOX family members in normal human epidermal keratinocytes (NHEK), IL-4/IL-13 treatment augments the expression of only DUOX1 mRNA. We next confirmed the IL-4/IL-13 induction of DUOX1 in NHEK at the mRNA and protein level using quantitative real-time PCR and Western blotting, respectively. In addition, we demonstrated that this augmented DUOX1 expression was accompanied by increased H2O2 production, which was significantly suppressed both by diphenyleneiodonium, an inhibitor of NADPH oxidase, and by small interfering RNA against DUOX1. Finally, we demonstrated that the increased expression of DUOX1 in IL-4/IL-13-treated NHEK augments STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B. These results revealed a novel role of IL-4/IL-13-induced DUOX1 expression in making a positive feedback loop for IL-4/IL-13 signaling in keratinocytes.

本文言語English
ページ(範囲)4762-4770
ページ数9
ジャーナルJournal of Immunology
186
8
DOI
出版ステータスPublished - 2011 4 15

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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