Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.
Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.
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DOI：
10.1371/journal.pone.0118286
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hayden PJ
中科院分区：
文献类型：
--
作者：
Bai J;Smock SL;Jackson GR Jr;MacIsaac KD;Huang Y;Mankus C;Oldach J;Roberts B;Ma YL;Klappenbach JA;Crackower MA;Alves SE;Hayden PJ
人呼吸道上皮细胞是人鼻病毒（HRV）的主要目标，HRV 是一种常见的感冒病原体，可引发大多数哮喘急性发作。本研究的目的是 1) 评估体外气液界面培养的 HRV 感染人气道上皮细胞模型，2) 使用该模型识别与哮喘本质上和/或 HRV 感染后相关的基因表达模式。气液界面 (ALI) 人气道上皮细胞培养物由 6 名哮喘捐献者和 6 名非哮喘捐献者制备。比较了鼻病毒 RV-A16 对 ALI 培养物的影响。使用 RNA-seq 技术进一步分析了暴露后 24 小时 HRV 感染后 ALI 培养物中全基因组基因表达的变化。分别通过 qPCR 和基于 Luminex 的蛋白质测定进一步评估细胞基因表达和细胞因子/趋化因子分泌。 ALI 培养物很容易被 HRV 感染。对 HRV 感染的 ALI 培养物进行 RNA 测序分析，确定了与哮喘特异性病毒反应相关的一组基因。这些基因与炎症途径、上皮结构和重塑以及纤毛组装和功能相关，包括先前描述的基因（例如CCL5、CXCL10和CX3CL1、MUC5AC、CDHR3），以及本研究中首次鉴定的新基因（例如CCRL1）。 ALI 培养的人气道上皮细胞受到 HRV 攻击，是研究 HRV 诱导的气道上皮细胞反应的有用转化模型，因为使用该模型的基因表达谱在很大程度上概括了临床 HRV 感染期间患者基因反应的一些重要模式。此外，我们的数据强调，气道上皮结构异常和炎症信号传导是两个重要的哮喘特征，HRV 感染可能会进一步加剧哮喘特征。
Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors. The effects of rhinovirus RV-A16 on ALI cultures were compared. Genome-wide gene expression changes in ALI cultures following HRV infection at 24 hours post exposure were further analyzed using RNA-seq technology. Cellular gene expression and cytokine/chemokine secretion were further evaluated by qPCR and a Luminex-based protein assay, respectively. ALI cultures were readily infected by HRV. RNA-seq analysis of HRV infected ALI cultures identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial structure and remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1, MUC5AC, CDHR3), and novel ones that were identified for the first time in this study (e.g. CCRL1). ALI-cultured human airway epithelial cells challenged with HRV are a useful translational model for the study of HRV-induced responses in airway epithelial cells, given that gene expression profile using this model largely recapitulates some important patterns of gene responses in patients during clinical HRV infection. Furthermore, our data emphasize that both abnormal airway epithelial structure and inflammatory signaling are two important asthma signatures, which can be further exacerbated by HRV infection.
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影响因子：
8
作者：
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影响因子：
4.4
作者：
El-Shazly, A;Berger, P;Tunon-de-Lara, JM
通讯作者：
Tunon-de-Lara, JM
DOI：
10.1165/rcmb.2011-0031oc
发表时间：
2011-11-01
影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1165/rcmb.2004-0417oc
发表时间：
2006-02-01
影响因子：
6.4
作者：
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通讯作者：
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