Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model
Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model
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大黄素减轻小鼠哮喘模型中交替激活的巨噬细胞和哮喘气道炎症
DOI：
10.1038/aps.2017.147
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发表时间：
2018-08-01
影响因子：
8.2
通讯作者：
Qian, Feng
中科院分区：
文献类型：
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作者：
Song, Yun-duan;Li, Xiao-zong;Qian, Feng
选择性激活的巨噬细胞（AAM）不仅与哮喘有关，而且还导致哮喘气道炎症和重塑。抑制AAM是治疗哮喘的替代治疗策略。在这项研究中，我们研究了大黄素（1，3，8-三羟基-6-甲基蒽醌），从掌叶大黄的根茎中分离，减轻哮喘气道炎症和减少AAM极化在小鼠哮喘模型。小鼠用含有尘螨、豚草和曲霉菌的三重过敏原混合物致敏。在DRA诱导的哮喘小鼠中，哮喘炎症显著增强。腹腔注射大黄素（20 mg· kg-1· d-1）可显著降低肺内嗜酸性粒细胞和淋巴细胞浸润、粘液分泌、血清IgE水平及支气管肺泡灌洗液中IL-4和IL-5水平。大黄素处理后，肺组织中AAM Ym-1、Fizz-1和AAM酶-1的活化标志物显著降低。在体外培养的小鼠骨髓源性巨噬细胞（BMDM）中，大黄素（2-50 μmol/L）呈剂量依赖性地抑制IL-4诱导的AAM极化和STAT 6磷酸化。总之，我们的研究结果表明，大黄素有效地改善哮喘气道炎症和AAM极化，因此，它可能成为一个潜在的药物治疗哮喘。
Alternatively activated macrophages (AAMs) are not only associated with asthma but also lead to asthmatic airway inflammation and remodeling. Inhibition of AAMs is an alternative therapeutic strategy for treating asthma. In this study we investigated whether emodin (1, 3, 8-trihydroxy-6-methylanthraquinone), isolated from the rhizome of Rheum palmatum, alleviated asthmatic airway inflammation and reduced AAM polarization in a murine asthma model. Mice were sensitized with a triple allergen mix containing dust mite, ragweed and aspergillus (DRA). In mice with DRA-induced asthma, asthmatic inflammation was significantly enhanced. Intraperitoneal injection of emodin (20 mg· kg− 1· d− 1, ip) 1 h prior to DRA challenge on days 12-14 significantly decreased pulmonary eosinophil and lymphocyte infiltration, mucus secretion and serum IgE production, as well as IL-4 and IL-5 production in bronchoalveolar lavage fluid. In response to emodin treatment, activated markers of AAM Ym-1, Fizz-1 and arginase-1 in the lung tissues were remarkably decreased. In mouse bone marrow-derived macrophages (BMDMs) in vitro, emodin (2–50 μmol/L) dose-dependently inhibited IL-4-induced AAM polarization and STAT6 phosphorylation. Collectively, our results suggest that emodin effectively ameliorates asthmatic airway inflammation and AAM polarization, and it may therefore become a potential agent for the treatment of asthma.