Mechanisms of virus-induced bronchial asthma exacerbations in children.

病毒引起儿童支气管哮喘恶化的机制。

基本信息

批准号：
18591159
负责人：
YAMAMOTO Shuichi
金额：
$ 2.43万
依托单位：
Saga University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591159/
关键词：
airway epithelial cells virus infection to the airway exacerbation of bronchial asthma CCL26 IL-4 IL-4 receptor アレルギー・ぜんそくウイルス感染症免疫学

项目摘要

We first examined the effect of IL-4, a Th2 cytokine, and IFN-g, a Th1 cytokine, on production of chemokine CCL26 in airway epithelial cells. IL-4 induced production of CCL26 from airway epithelial cells. IFN-g inhibited IL-4-induced CCL26 production when added simultaneously. On the other hands, prior stimulation with INF-g to airway epithelial cells enhanced IL-4-induced CCL26 production. This effect was resulted from up-regulation of IL-4 receptor system. IFN-g enhanced mRNA expression of both IL-4Ra and IL-2Rg. Flowcytometry analysis also revealed enhanced protein expression of IL-4Ra and IL-2Rg at cell surface. Enhanced expression of IL-4R leads to enhanced IL-4-induced CCL26 production through Jak-STAT signaling system.Then, a model of airway virus infection was used to examine the mechanisms of virus-induced bronchial asthma exacerbations. Polyinocinic-citidiric acid (poly (IC)), a double-stranded RNA, was transfected to cultured airway epithelial cells including primary cells. … More By the transfection of poly (IC), airway epithelial cells produced IL-8 and RANTES suggesting that this model can be used as airway virus infection. Poly (IC) alone did not influence production of CCL26 from airway epithelial cells, however, IL-4-induced CCL26 production was significantly enhanced in poly (IC) -transfected cells. We also observed enhanced IL-4R by transfection of poly (IC) in airway epithelial cells. IL-4Ra and IL-2Rg chains were up-regulated in both mRNA and protein levels. Enhanced IL-4R expression resulted in enhanced production of CCL26.These results might suggest that during virus infection, IFN-g produced from lymphocytes infiltrated to the airway triggered enhanced eosinophilic airway inflammation by enhanced production of CCL26 from airway epithelial cells. Virus infection itself also influences expression of IL-4R system. Thus, we speculated that virus airway infection might trigger not only neutrophilic airway infiltration but also eosinophilic airway infiltration. Less

我们首先检查了 Th2 细胞因子 IL-4 和 Th1 细胞因子 IFN-g 对气道上皮细胞中趋化因子 CCL26 产生的影响，IL-4 诱导 IFN-g 抑制的气道上皮细胞产生 CCL26。当同时添加时，-4诱导CCL26产生。另一方面，预先用INF-g刺激气道上皮细胞增强了IL-4诱导的CCL26产生。 IL-4受体系统的上调导致IL-4Ra和IL-2Rg的mRNA表达增强，流式细胞术分析还显示细胞表面的IL-4Ra和IL-2Rg的蛋白表达增强。 IL-4R的表达通过Jak-STAT信号系统导致IL-4诱导的CCL26产生增强。然后，使用气道病毒感染模型来研究病毒诱导的支气管哮喘的机制聚肌酸柠檬酸 (poly (IC)) 是一种双链 RNA，被转染至培养的气道上皮细胞，包括原代细胞……通过转染 Poly (IC)，气道上皮细胞产生 IL-8 和 RANTES。表明该模型可用作气道病毒感染，单独的Poly (IC)不影响气道上皮细胞产生CCL26，然而，IL-4诱导。我们还观察到，通过转染poly (IC)，气道上皮细胞中的CCL26 产量显着增强，IL-4Ra 和IL-2Rg 链的mRNA 和蛋白质均上调。 IL-4R 表达水平的增强导致 CCL26 的产生增强。这些结果可能表明，在病毒感染期间，浸润到气道的淋巴细胞产生的 IFN-g 引发了嗜酸性粒细胞的增强。病毒感染本身会影响IL-4R系统的表达，从而导致气道炎症，因此，我们推测病毒气道感染不仅会引发中性粒细胞浸润，还会引发嗜酸性粒细胞浸润。