Increased Cytokine Response of Rhinovirus-infected Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
Increased Cytokine Response of Rhinovirus-infected Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
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DOI：
10.1164/rccm.200911-1673oc
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发表时间：
2010-08-01
影响因子：
24.7
通讯作者：
Sajjan, Umadevi
中科院分区：
文献类型：
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作者：
Schneider, Dina;Ganesan, Shyamala;Sajjan, Umadevi
原理：气道炎症是慢性阻塞性肺疾病（COPD）的主要特征。COPD急性加重往往是由鼻病毒（RV）infection.Objectives：我们假设，从COPD患者的气道上皮细胞保持一个促炎表型与对照subjects相比，导致更大的RV responsesMethods：从12例COPD患者和10个移植供体的气管支气管组织中分离细胞。8例COPD患者有重度肺气肿，3例有轻度至中度肺气肿，1例无肺气肿。所有患者均有中度至重度气流阻塞，6例符合慢性支气管炎标准或前一年至少有一次加重。使细胞在空气-液体界面生长并用RV血清型39感染。ELISA法检测细胞因子和IFN的表达。选定的基因参与炎症，氧化应激和蛋白水解进行了评估，通过聚焦基因阵列和实时聚合酶链反应.测量和主要结果：与对照组相比，COPD患者的细胞表现出增加的mRNA表达的基因参与氧化应激和病毒感染的反应，包括NOX 1，DUOXA 2，MMP 12，ICAM 1，DDX 58/RIG-I，STAT 1，和STAT 2。COPD细胞显示IL-6、IL-8/CXCL 8和生长相关癌基因-α/CXCL 1的基线和RV刺激蛋白水平升高。COPD细胞显示RV感染后病毒滴度和拷贝数增加，尽管IL-29/IFN-λ 1、IL-28 A/IFN-λ 2和IFN诱导蛋白-10/CXCL10蛋白水平增加。最后，RV感染的COPD培养物显示IL 28 A/IFN λ 2、IL 29/IFN λ 1、IFIH 1/MDA 5、DDX 58/RIG-1、DUOX 1、DUOX 2、IRF 7、STAT 1和STAT 2的mRNA表达增加。结论：尽管IFN应答增加，但COPD患者的气道上皮细胞显示更高的细胞因子表达水平和对RV感染的易感性增加。
Rationale: Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection.Objectives: We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responsesMethods: Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at air-liquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction.Measurements and Main Results: Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RV-stimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-alpha/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-lambda 1, IL-28A/IFN-lambda 2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFN lambda 2, IL29/IFN lambda 1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2.Conclusions: Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.