Resolvin E3 attenuates allergic airway inflammation via the interleukin-23-interleukin-17A pathway

被引:35
作者
Sato, Makiko [1 ,2 ]
Aoki-Saito, Haruka [1 ]
Fukuda, Hayato [3 ]
Ikeda, Hiroyuki [4 ,5 ]
Koga, Yasuhiko [1 ]
Yatomi, Masakiyo [1 ]
Tsurumaki, Hiroaki [1 ]
Maeno, Toshitaka [1 ]
Saito, Tsugumichi [2 ]
Nakakura, Takashi [6 ]
Mori, Tetsuya [7 ]
Yanagawa, Masataka [8 ]
Abe, Mitsuhiro [8 ]
Sako, Yasushi [8 ]
Dobashi, Kunio [1 ]
Ishizuka, Tamotsu [9 ]
Yamada, Masanobu [2 ]
Shuto, Satoshi [4 ,5 ]
Hisada, Takeshi [1 ,10 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Resp Med, 3-39-22 Showa Machi, Maebashi, Gunma 3718514, Japan
[2] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Gunma, Japan
[3] Nagasaki Univ, Grad Sch Biomed Sci, Nagasaki, Japan
[4] Hokkaido Univ, Fac Pharmaceut Sci, Sapporo, Hokkaido, Japan
[5] Hokkaido Univ, Ctr Res & Educ Drug Discovery, Sapporo, Hokkaido, Japan
[6] Teikyo Univ, Dept Anat, Tokyo, Japan
[7] Takasaki Univ Hlth & Welf, Fac Pharm, Lab Allergy & Immunol, Gunma, Japan
[8] RIKEN, Cluster Pioneering Res, Cellular Informat Lab, Saitama, Japan
[9] Univ Fukui, Fac Med Sci, Dept Internal Med 3, Fukui, Japan
[10] Gunma Univ, Grad Sch Hlth Sci, Gunma, Japan
基金
日本学术振兴会;
关键词
house dust mite; omega-3 fatty acid; IL-17A; LEUKOTRIENE B-4 RECEPTOR; RESOLUTION; IL-23; CELLS; E1; ASTHMA; PSORIASIS; MODEL; FISH;
D O I
10.1096/fj.201900283R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We investigated the effects of resolvin E (RvE) 1, RvE2, and RvE3 on IL-4- and IL-33-stimulated bone marrow-derived dendritic cells (BMDCs) from house dust mite (HDM)-sensitized mice. We also investigated the role of RvE3 in a murine model of HDM-induced airway inflammation. In vitro, BMDCs from HDM-sensitized mice were stimulated with IL-4 and IL-33 and then treated with RvE1, RvE2, RvE3, or vehicle. RvE1, RvE2, and RvE3 suppressed IL-23 release from BMDCs. In vivo, RvE3 administrated to HDM-sensitized and challenged mice in the resolution phase promoted a decline in total numbers of inflammatory cells and eosinophils, reduced levels of IL-23 and IL-17 in lavage fluid, and suppressed IL-23 and IL-17A mRNA expression in lung and peribronchial lymph nodes. RvE3 also reduced resistance in the lungs of HDM-sensitized mice. A NanoBiT beta-arrestin recruitment assay using human embryonic kidney 293 cells revealed that pretreatment with RvE3 suppressed the leukotriene B4 (LTB4)-induced beta-arrestin 2 binding to LTB4 receptor 1 (BLT1R), indicating that RvE3 antagonistically interacts with BLT1R. Collectively, these findings indicate that RvE3 facilitates the resolution of allergic airway inflammation, partly by regulating BLT1R activity and selective cytokine release by dendritic cells. Our results accordingly identify RvE3 as a potential therapeutic target for the management of asthma.
引用
收藏
页码:12750 / 12759
页数:10
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