Mechanisms of virus-induced bronchial asthma exacerbations in children.

我们首先检测了Th2细胞因子IL-4和Th1细胞因子IFN-g对呼吸道上皮细胞产生趋化因子CCL26的影响。IL-4诱导呼吸道上皮细胞产生CCL26。同时加入干扰素-g可抑制IL-4诱导的CCL26的产生。另一方面，预先给予干扰素-g刺激气道上皮细胞可增加IL-4诱导的CCL26的产生。这种作用是由于IL-4受体系统上调所致。干扰素-g可增强IL-4Ra和IL-2Rg的mRNA表达。流式细胞仪分析显示细胞表面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产生增加。然后，采用呼吸道病毒感染模型来研究病毒诱导的哮喘加重的机制。将多聚柠檬酸(Poly(IC))双链RNA导入包括原代细胞在内的培养的呼吸道上皮细胞。…更多地通过多聚IC的转染，呼吸道上皮细胞产生IL-8和RANTES，提示该模型可用于呼吸道病毒感染。Poly(IC)单独作用不影响呼吸道上皮细胞CCL26的产生，而IL-4诱导的Poly(IC)转染组CCL26的产生显著增加。我们还观察到通过在呼吸道上皮细胞中转染聚(IC)来增强IL-4R。IL-4Ra和IL-2Rg链在mRNA和蛋白水平均上调。IL-4R表达增强导致CCL26产生增加，提示在病毒感染过程中，淋巴细胞产生的干扰素-g可能通过促进呼吸道上皮细胞产生CCL26而引发嗜酸性气道炎症。病毒感染本身也影响IL-4R系统的表达。因此，我们推测病毒呼吸道感染不仅可能触发嗜中性粒细胞的气道渗透，而且还可能触发嗜酸性的气道渗透。较少

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