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⁺, CD11c^low, 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.
Int Arch Allergy Immunol

中文翻译：

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非抗生素大环内酯EM900可以减轻肥胖相关哮喘小鼠模型中屋尘螨引起的气道炎症。

简介：肥胖相关哮喘的特征在于2型低气道炎症。我们先前显示，EM900是一种12元非抗生素大环内酯类药物，可在哮喘急性发作的小鼠模型中抑制气道炎症。这项研究的目的是阐明EM900在肥胖相关哮喘中的作用。方法：给BALB / c小鼠喂低脂饮食（LFD）或高脂饮食（HFD）。对小鼠进行鼻内敏化，并用室内尘螨（HDM）攻击，并口服EM900。使用支气管肺泡灌洗液（BALF）中的炎症细胞评估气道炎症。通过ELISA检查肺组织中的细胞因子。肺间质巨噬细胞（CD45 ⁺，^低CD11c，CD11b ⁺和Ly6c通过流式细胞术计数来自肺组织的单个细胞中的^-）。结果：与LFD组相比，HFD中的体重显着增加。在HFD-HDM组中，通过EM900给药，BALF中的总细胞数以及嗜中性粒细胞和嗜酸性粒细胞的数量被显着抑制。与LFD-HDM组相比，HFD-HDM组的白细胞介素（IL）-17A水平升高，尽管差异没有统计学意义。在HFD-HDM组中，通过EM900给药可显着抑制IL-17A，巨噬细胞炎性蛋白2，IL-1β，IL-5的水平以及肺组织中活化，正常T细胞表达和分泌的调节。在HFD-HDM组中，通过EM900给药，肺间质巨噬细胞的百分比显着降低。结论：在这种肥胖相关的哮喘模型中，EM900减轻了2型和2型低气道炎症。这些结果表明，EM900可能是治疗肥胖相关哮喘的候选药物。
Int Arch过敏免疫