Resolvin E3 attenuates allergic airway inflammation via the interleukin‐23‐interleukin‐17A pathway
Resolvin E3 attenuates allergic airway inflammation via the interleukin‐23‐interleukin‐17A pathway
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DOI：
10.1096/fj.201900283r
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发表时间：
2019-08
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通讯作者：
Makiko Sato;Haruka Aoki-Saito;H. Fukuda;H. Ikeda;Yasuhiko Koga;Masakiyo Yatomi;Hiroaki Tsurumaki;T. Maeno;Tsugumichi Saito;T. Nakakura;T. Mori;Masataka Yanagawa;M. Abe;Y. Sako;K. Dobashi;T. Ishizuka;M. Yamada;S. Shuto;T. Hisada
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作者：
Makiko Sato;Haruka Aoki-Saito;H. Fukuda;H. Ikeda;Yasuhiko Koga;Masakiyo Yatomi;Hiroaki Tsurumaki;T. Maeno;Tsugumichi Saito;T. Nakakura;T. Mori;Masataka Yanagawa;M. Abe;Y. Sako;K. Dobashi;T. Ishizuka;M. Yamada;S. Shuto;T. Hisada
我们研究了解决素E(RVE)1、RvE2和RvE3对IL-4和IL-33刺激的屋尘螨(HDM)致敏小鼠骨髓来源的树突状细胞(BMDCs)的影响。我们还研究了RvE3在HDM诱导的小鼠呼吸道炎症模型中的作用。在体外，用IL-4和IL-33刺激HDM致敏小鼠的BMDCs，然后用RvE1、RvE2、RvE3或赋形剂处理。RvE1、RvE2和RvE3抑制BMDCs释放IL-23。在体内，RvE3对HDM致敏和激发的HDM致敏和激发的小鼠，促进炎症细胞总数和嗜酸性粒细胞总数的减少，降低灌洗液中IL-23和IL-17的水平，并抑制肺和支气管周围淋巴结中IL-23和IL-17A的mRNA表达。RvE3还降低了HDM致敏小鼠肺部的抵抗力。人胚胎肾293细胞纳米β-arrestin募集实验显示，rvE3可抑制白三烯B4诱导的β-arrestin 2与LTb4受体1(BLT1R)的结合，表明RvE3与BLT1R有拮抗作用。总之，这些发现表明RvE3促进过敏性呼吸道炎症的缓解，部分是通过调节BLT1R活性和树突状细胞选择性释放细胞因子来实现的。因此，我们的结果确定RvE3是治疗哮喘的潜在治疗目标。--佐藤、M.、青木齐藤、H.、福田、H.、池田、H.、古贺、Y.、YATOM、M.、Tsurumaki、H.、Maeno、T.、Saito、T.、Nakura、T.、Mori、T.、柳川、M.、Abe、M.、Sako、Y.、Dobashi、K.、Ishizuka、T.、Yamada、M.、Shuto、S.、Hisada、T.Resolvin E3通过IL-23-IL-17A途径减轻过敏性呼吸道炎症。FASE B J.33,12750-12759(2019年)。Www.fasebj.org
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 β‐arrestin recruitment assay using human embryonic kidney 293 cells revealed that pretreatment with RvE3 suppressed the leukotriene B4 (LTB4)‐induced β‐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.—Sato, M., Aoki‐Saito, H., Fukuda, H., Ikeda, H., Koga, Y., Yatomi, M., Tsurumaki, H., Maeno, T., Saito, T., Nakakura, T., Mori, T., Yanagawa, M., Abe, M., Sako, Y., Dobashi, K., Ishizuka, T., Yamada, M., Shuto, S., Hisada, T. Resolvin E3 attenuates allergic airway inflammation via the interleukin‐23‐interleukin‐17A pathway. FASEB J. 33, 12750–12759 (2019). www.fasebj.org