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Emodin alleviates alternatively activated macrophage and asthmatic airway inflammation in a murine asthma model

机译:大黄素缓解鼠哮喘模型中交替激活的巨噬细胞和哮喘气道炎症

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摘要

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.
机译:另外,活化的巨噬细胞(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是治疗哮喘的另一种治疗策略。在这项研究中,我们调查了从鼠李大黄根茎中分离出的大黄素(1,3,8-三羟基-6-甲基蒽醌)是否能减轻鼠哮喘模型中的哮喘气道炎症并降低AAM极化。用含有尘螨,豚草和曲霉菌(DRA)的三重过敏原混合物使小鼠致敏。在患有DRA诱发的哮喘的小鼠中,哮喘炎症显着增强。大黄素激发前12到14天腹腔注射大黄素(20 mg·kg −1 ·d -1 ,ip),可显着降低肺部嗜酸性粒细胞和淋巴细胞浸润,粘液分泌和血清IgE产生,以及支气管肺泡灌洗液中的IL-4和IL-5产生。响应大黄素的处理,肺组织中AAM Ym-1,Fizz-1和精氨酸酶-1的活化标记显着降低。在体外小鼠骨髓源性巨噬细胞(BMDM)中,大黄素(2–50μmol/ L)剂量依赖性地抑制IL-4诱导的AAM极化和STAT6磷酸化。总体而言,我们的结果表明,大黄素可有效改善哮喘气道炎症和AAM极化,因此可能成为治疗哮喘的潜在药物。

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