MUC18 Regulates Lung Rhinovirus Infection and Inflammation.
MUC18 Regulates Lung Rhinovirus Infection and Inflammation.
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DOI：
10.1371/journal.pone.0163927
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Chu HW
中科院分区：
文献类型：
--
作者：
Berman R;Jiang D;Wu Q;Stevenson CR;Schaefer NR;Chu HW
MUC18 在哮喘和 COPD 患者的肺部表达上调。它已被证明在病毒感染期间培养的人气道上皮细胞和肺部细菌感染期间的小鼠中具有促炎功能。然而，MUC18 在病毒感染中的体内作用仍知之甚少。本研究的目的是确定 MUC18 在呼吸道鼻病毒感染期间的体内功能。 Muc18 野生型 (WT) 和基因敲除 (KO) 小鼠感染人鼻病毒 1B (HRV-1B)，并在 1 天后处死以确定炎症和抗病毒反应。为了检查 Muc18 对病毒感染的直接影响，从 WT 和 KO 小鼠中分离的气管上皮细胞在气液界面下生长并用 HRV-1B 感染。最后，在人气道上皮细胞 (AEC) 中进行 siRNA 介导的 MUC18 敲低，以确定 MUC18 对人气道对 HRV-1B 反应的影响。与 WT 小鼠相比，Muc18 KO 小鼠的病毒载量和中性粒细胞炎症均显着降低。在体外环境中，与 WT 小鼠相比，Muc18 KO 小鼠气道上皮细胞中的病毒载量显着降低，抗病毒基因表达更高。此外，与对照相比，在MUC18敲低的人类AEC中，病毒载量降低，抗病毒基因表达增加。我们的研究首次在鼻病毒感染的体内小鼠模型中证明了 MUC18 的促炎和促病毒功能。
MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B. Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls. Our study is the first to demonstrate MUC18’s pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection.
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DOI：
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发表时间：
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期刊：
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