Mechanisms of virus-induced bronchial asthma exacerbations in children.

我们首先检测了IL-4 （Th2细胞因子）和IFN-g （Th1细胞因子）对气道上皮细胞趋化因子CCL26产生的影响。IL-4诱导气道上皮细胞产生CCL26。同时加入IFN-g可抑制il -4诱导的CCL26的产生。另一方面，事先用INF-g刺激气道上皮细胞可增强il -4诱导的CCL26的产生。这种作用是由于IL-4受体系统的上调所致。IFN-g增强了IL-4Ra和IL-2Rg mRNA的表达。流式细胞术分析显示细胞表面IL-4Ra和IL-2Rg蛋白表达增强。IL-4R表达增强通过Jak-STAT信号系统导致il -4诱导的CCL26生成增强。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加重的机制。将双链RNA polyinocic -citidiric acid （poly (IC)）转染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，提示该模型可用于气道病毒感染。单独Poly （IC）不影响气道上皮细胞CCL26的产生，然而，il -4诱导的CCL26的产生在Poly （IC）转染的细胞中显著增强。我们还通过转染poly （IC）在气道上皮细胞中观察到IL-4R的增强。IL-4Ra和IL-2Rg链mRNA和蛋白水平均上调。IL-4R表达增强导致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通过增强气道上皮细胞产生的CCL26引发了增强的嗜酸性气道炎症。病毒感染本身也影响IL-4R系统的表达。因此，我们推测病毒气道感染不仅可能引发嗜中性粒细胞气道浸润，也可能引发嗜酸性粒细胞气道浸润。少

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