論文

国際誌
2019年11月

Prostaglandin E2 (PGE2)-EP2 signaling negatively regulates murine atopic dermatitis-like skin inflammation by suppressing thymic stromal lymphopoietin expression.

The Journal of allergy and clinical immunology
  • Yu Sawada
  • ,
  • Tetsuya Honda
  • ,
  • Satoshi Nakamizo
  • ,
  • Saeko Nakajima
  • ,
  • Yumi Nonomura
  • ,
  • Atsushi Otsuka
  • ,
  • Gyohei Egawa
  • ,
  • Tomohiro Yoshimoto
  • ,
  • Motonobu Nakamura
  • ,
  • Shuh Narumiya
  • ,
  • Kenji Kabashima

144
5
開始ページ
1265
終了ページ
1273
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.jaci.2019.06.036

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease of type 2 immunity. Keratinocyte-derived cytokines, including thymic stromal lymphopoietin (TSLP) and IL-33, are considered to induce the development of AD. Production of prostanoids, a family of lipid mediators, is increased in AD lesions. However, their physiologic functions remain to be clarified. OBJECTIVES: We sought to elucidate the functions of prostanoids in the development of AD. METHODS: The roles of prostanoids were investigated in a mouse model of AD induced by repeated application of hapten and PAM212, a keratinocyte cell line. RESULTS: Application of indomethacin, which blocks prostanoid synthesis, leads to enhanced TSLP and IL-33 production in the skin, increased serum IgE levels, and exacerbation of skin inflammation in this AD model. The skin inflammation was attenuated in TSLP receptor-deficient mice but not in IL-33-deficient mice, and the indomethacin-enhanced type 2 immune responses were abolished in TSLP receptor-deficient mice. Indomethacin increased protease-activated receptor 2-mediated TSLP production in keratinocytes in vitro, and prostaglandin E2 reversed the increase in TSLP levels through its receptor, the prostaglandin E2 receptor (EP2), by downregulating surface expression of protease-activated receptor 2. Administration of an EP2 agonist canceled indomethacin-enhanced TSLP production and type 2 immune responses in the skin, whereas an EP2 antagonist caused an enhancement of TSLP production and type 2 immune responses in the skin. CONCLUSION: Prostaglandin E2-EP2 signaling negatively regulates murine AD-like skin inflammation by suppressing TSLP expression.

リンク情報
DOI
https://doi.org/10.1016/j.jaci.2019.06.036
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31301371
ID情報
  • DOI : 10.1016/j.jaci.2019.06.036
  • PubMed ID : 31301371

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