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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

我们首先检测了IL-4（一种Th 2细胞因子）和IFN-g（一种Th 1细胞因子）对气道上皮细胞中趋化因子CCL 26产生的影响。IL-4诱导气道上皮细胞产生CCL 26。当同时加入时，IFN-g抑制IL-4诱导的CCL 26产生。另一方面，预先用INF-g刺激气道上皮细胞增强IL-4诱导的CCL 26产生。这种作用是通过上调IL-4受体系统而实现的。IFN-γ可促进IL-4 Ra和IL-2 Rg的mRNA表达。流式细胞术分析还显示在细胞表面的IL-4 Ra和IL-2 Rg的蛋白表达增强。IL-4 R的表达增强通过Jak-STAT信号系统导致IL-4诱导的CCL 26的产生增强。将双链RNA多聚肌苷酸（poly（IC））转染培养的气道上皮细胞（包括原代细胞）。 ...更多信息经poly（IC）转染后，气道上皮细胞产生IL-8和RANTES，提示该模型可用于气道病毒感染。单独的Poly（IC）并不影响气道上皮细胞产生CCL 26，然而，IL-4诱导的CCL 26产生在poly（IC）转染的细胞中显著增强。我们还观察到通过在气道上皮细胞中转染poly（IC）而增强的IL-4 R。IL-4 Ra和IL-2 Rg链在mRNA和蛋白水平上均上调。IL-4 R表达增强导致CCL 26产生增加，提示病毒感染时，气道浸润淋巴细胞产生的IFN-g可能通过增加气道上皮细胞产生CCL 26而引发嗜酸性粒细胞性气道炎症。病毒感染本身也影响IL-4 R系统的表达。因此，我们推测病毒感染不仅可能引起嗜酸性粒细胞的气道浸润，而且可能引起嗜酸性粒细胞的气道浸润。少