Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection.

Cystic fibrosis and normal human airway epithelial cell response to influenza a viral infection.
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囊性纤维化和正常人气道上皮细胞对甲型流感病毒感染的反应。

DOI:
10.1089/jir.2006.26.609
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发表时间:
2006
期刊:
Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research
影响因子:
--
通讯作者:
Erzurum,SerpilC
Erzurum,SerpilC
中科院分区:
--
文献类型:
--
作者:
Xu,Weiling;Zheng,Shuo;Goggans,TannishiaM;Kiser,Patti;Quinones-Mateu,MiguelE;Janocha,AllisonJ;Comhair,SuzyAA;Slee,Roger;Williams,BryanRG;Erzurum,SerpilC

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病毒感染可导致囊性纤维化(CF)患儿严重的呼吸道疾病。CF细胞对病毒更敏感,部分原因是气道上皮细胞信号转导和转录激活因子1(Stat 1)的激活受损。由于Stat 1是抗病毒防御的基本调节因子,我们假设与正常(NL)相比,CF上皮的抗病毒防御可能存在多种改变。为了全面了解粘膜宿主对流感的反应并表征CF和NL对流感反应之间的差异,使用干扰素(IFN)刺激的基因/Au/双链RNA(dsRNA)微阵列或定量实时聚合酶链反应(PCR)评价了甲型流感感染后原代人气道上皮细胞(HAEC)的基因表达谱。NL(228个基因)和CF(101个基因)中的基因表达被流感显著改变,基因应答模式相似,但CF中应答基因的总体数量较少(p< 0.05)。感染后24 h,CF细胞IFN相关的抗病毒基因的表达减少,而感染后1 h,CF细胞炎性细胞因子基因的表达增加。总之,较少的抗病毒药物和较大的早期炎症反应可能导致CF病毒感染患者的严重呼吸道疾病。
Viral infections produce severe respiratory morbidity in children with cystic fibrosis (CF). CF cells are more susceptible to virus in part because of impaired airway epithelial activation of signal transducer and activator of transcription 1 (Stat1). As Stat1 is a fundamental regulator of antiviral defenses, we hypothesized that there may be multiple alterations in the antiviral defense of CF epithelium compared with normal (NL). To obtain a comprehensive view of mucosal host responses to influenza and characterize the difference between CF and NL responses to influenza, gene expression profiles of primary human airway epithelial cells (HAEC) were evaluated using an interferon (IFN)-stimulated genes/AU/double-stranded RNA (dsRNA) microarray or quantitative real-time polymerase chain reaction (PCR) following influenza A infection. Gene expression was significantly modified by influenza in NL (228 genes) and CF (101 genes), with a similar pattern of gene response but with overall less numbers of responsive genes in CF (p< 0.05). Moreover, CF cells had less IFNrelated antiviral gene induction at 24 h but greater inflammatory cytokine gene induction at 1 h after infection. Taken together, the lesser antiviral and greater early inflammatory response likely contribute to the severe respiratory illness of CF patients with viral infections.
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发表时间: 2002
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