Hemin ameliorates influenza pneumonia by attenuating lung injury and regulating the immune response
Hemin ameliorates influenza pneumonia by attenuating lung injury and regulating the immune response
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DOI：
10.1016/j.ijantimicag.2016.09.030
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发表时间：
2017-01-01
影响因子：
10.8
通讯作者：
Wang, Jianwei
中科院分区：
文献类型：
--
作者：
Wang, Conghui;Zhang, Yanjing;Wang, Jianwei
血红素加氧酶-1（HO-1）的诱导剂、激活剂和底物氯化血红素（hemin）在体内外均具有抗流感病毒的活性。以人肺癌细胞株A549为研究对象，探讨氯化血红素对甲型流感病毒（IAV）体外增殖的影响。使用小鼠模型来检查氯化血红素的体内活性。观察指标包括小鼠存活率和体重、肺部病毒载量和病理学检查以及全身和局部免疫反应的特征。结果表明，氯化血红素能诱导A549细胞HO-1表达，并能抑制IAV在体外的复制。体内实验结果表明，注射氯化血红素对IAV感染引起的小鼠死亡和体重减轻有保护作用。在流感肺炎的初始和进行性阶段（分别在病毒感染后1天和4天）施用氯化血红素，并且在两种条件下均显示出显著的抗流感活性。然而，结果表明，虽然氯化血红素可以诱导HO-1在体内的表达，它不能抑制IAV在体内的复制。病理学检查表明，氯化血红素能明显减轻IAV引起的肺组织损伤。进一步的研究表明，氯化血红素可通过减少IAV感染引起的淋巴细胞减少和局部炎性细胞因子升高来调节IAV感染的免疫应答。本研究表明，氯化血红素具有治疗IAV感染的潜力，其作用可能是由于减轻肺损伤和调节免疫反应。(C)2016 Elsevier B. V.和国际化疗学会。All rights reserved.
The anti-influenza activity of hemin, an inducer, activator and the substrate of heme oxygenase-1 (HO-1), was examined both in vitro and in vivo. The human lung carcinoma cell line A549 was used to evaluate the in vitro effect of hemin on influenza A virus (IAV) replication. A mouse model was used to examine the in vivo activity of hemin. Observation indexes included survival rate and body weight of mice, virus load and pathological examination of the lungs, and characterization of the systemic and local immune responses. The results showed that hemin could induce HO-1 expression in A549 cells and inhibit IAV replication in vitro. The in vivo results showed that injection of hemin could protect mice from death and body weight loss caused by IAV infection. Hemin was administered both at initial and progressive stages of influenza pneumonia (1 day and 4 days after virus infection, respectively) and showed significant anti-influenza activity under both conditions. However, the results showed that although hemin could induce HO-1 expression in vivo, it could not inhibit IAV replication in vivo. Pathological examination showed that hemin significantly attenuated lung tissue injury caused by IAV. Further study showed that hemin could regulate the immune response to IAV infection by reducing lymphocytopenia and local inflammatory cytokine increases caused by IAV infection. This study shows that hemin has the potential for the treatment of IAV infection and its effect may be due to attenuation of lung injury and regulation of the immune response. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.