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The Nonantibiotic Macrolide EM900 Attenuates House Dust Mite-Induced Airway Inflammation in a Mouse Model of Obesity-Associated Asthma

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2020年
DOI:
10.1159/000508709
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
○Hironori Sadamatsu, Koichiro Takahashi, Hiroki Tashiro, Yuki Kurihara, Go Kato, Masaru Uchida, Yoshihiko Noguchi, Keigo Kurata, Satoshi Ōmura, Toshiaki Sunazuka, Shinya Kimura, Naoko Sueoka-Aragane
題名:
The Nonantibiotic Macrolide EM900 Attenuates House Dust Mite-Induced Airway Inflammation in a Mouse Model of Obesity-Associated Asthma
発表情報:
Int Arch Allergy Immunol 巻: 181 号: 9 ページ: 665-674
キーワード:
概要:
Introduction: Obesity-associated asthma is characterized by type 2-low airway inflammation. We previously showed that EM900, which is a 12-membered nonantibiotic macrolide, suppressed airway inflammation in a mouse model of asthma exacerbation. The aim of this study was to clarify the effects of EM900 in obesity-associated asthma. Methods: BALB/c mice were fed a low-fat diet (LFD) or high-fat diet (HFD). Mice were intranasally sensitized and challenged with house dust mites (HDMs) and were orally administered EM900. Airway inflammation was assessed using inflammatory cells in bronchoalveolar lavage (BALF). Cytokines were examined by ELISA in lung tissues. Lung interstitial macrophages (CD45+, CD11clow, CD11b+, and Ly6c-) were counted by flow cytometry in single cells from lung tissues. Results: Body weight increased significantly in the HFD compared with the LFD group. The total cell count and numbers of neutrophils and eosinophils in BALF were significantly suppressed by EM900 administration in the HFD-HDM group. The levels of interleukin (IL)-17A were increased in the HFD-HDM group compared with the LFD-HDM group, although the difference did not reach statistical significance. The levels of IL-17A, macrophage inflammatory protein 2, IL-1β, IL-5, and regulated on activation, normal T cell expressed and secreted in lung tissue were significantly suppressed by EM900 administration in the HFD-HDM group. The percentage of interstitial macrophages in lungs was significantly decreased by EM900 administration in the HFD-HDM group. Conclusion: Both type 2 and type 2-low airway inflammation were attenuated by EM900 in this obesity-associated asthma model. These results show that EM900 might be a candidate agent for the treatment of obesity-associated asthma.
抄録:

英語フィールド

Author:
○Hironori Sadamatsu, Koichiro Takahashi, Hiroki Tashiro, Yuki Kurihara, Go Kato, Masaru Uchida, Yoshihiko Noguchi, Keigo Kurata, Satoshi Ōmura, Toshiaki Sunazuka, Shinya Kimura, Naoko Sueoka-Aragane
Title:
The Nonantibiotic Macrolide EM900 Attenuates House Dust Mite-Induced Airway Inflammation in a Mouse Model of Obesity-Associated Asthma
Announcement information:
Int Arch Allergy Immunol Vol: 181 Issue: 9 Page: 665-674
An abstract:
Introduction: Obesity-associated asthma is characterized by type 2-low airway inflammation. We previously showed that EM900, which is a 12-membered nonantibiotic macrolide, suppressed airway inflammation in a mouse model of asthma exacerbation. The aim of this study was to clarify the effects of EM900 in obesity-associated asthma. Methods: BALB/c mice were fed a low-fat diet (LFD) or high-fat diet (HFD). Mice were intranasally sensitized and challenged with house dust mites (HDMs) and were orally administered EM900. Airway inflammation was assessed using inflammatory cells in bronchoalveolar lavage (BALF). Cytokines were examined by ELISA in lung tissues. Lung interstitial macrophages (CD45+, CD11clow, CD11b+, and Ly6c-) were counted by flow cytometry in single cells from lung tissues. Results: Body weight increased significantly in the HFD compared with the LFD group. The total cell count and numbers of neutrophils and eosinophils in BALF were significantly suppressed by EM900 administration in the HFD-HDM group. The levels of interleukin (IL)-17A were increased in the HFD-HDM group compared with the LFD-HDM group, although the difference did not reach statistical significance. The levels of IL-17A, macrophage inflammatory protein 2, IL-1β, IL-5, and regulated on activation, normal T cell expressed and secreted in lung tissue were significantly suppressed by EM900 administration in the HFD-HDM group. The percentage of interstitial macrophages in lungs was significantly decreased by EM900 administration in the HFD-HDM group. Conclusion: Both type 2 and type 2-low airway inflammation were attenuated by EM900 in this obesity-associated asthma model. These results show that EM900 might be a candidate agent for the treatment of obesity-associated asthma.


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