ROLE OF RSV INFECTION AND ENDOTOXIN IN AIRWAY INFLAMMATION

呼吸道合胞病毒(RSV)是引起下呼吸道感染的重要原因 儿童呼吸道疾病。呼吸道合胞病毒感染的主要部位 是呼吸道上皮细胞，它与一种优势的 支气管肺泡灌洗液中的中性粒细胞。中性粒细胞的存在 与呼吸道中IL-8的增加是平行的，IL-8是一种有效的 中性粒细胞趋化因子。呼吸道合胞病毒的一个有趣的临床特征 感染之后是呼吸道反应性的增加。 与该计划相关的是，这种增加的呼吸道反应性包括 对含有内毒素的粉尘有更强的反应。在我们的预赛中 研究发现，呼吸道上皮对内毒素的反应不是通过 释放IL-8。然而，如果上皮细胞感染了RSV，就会有 当加入内毒素时，IL-8的释放显著增加 单层。基于这些观察，我们假设RSV 感染上调了呼吸道上皮对内毒素的反应。 因为我们不能研究所有相关的机制，因为它们与 在这一假设下，我们决定提出以下问题：1)RSV 感染上调呼吸道上皮对内毒素的反应？2) 呼吸道合胞病毒诱导的对内毒素的反应是否会导致 关键的丝裂原活化蛋白激酶(MAPK)通路？3)是 这些MAPK通路的激活与特异性的激活有关 调节IL-8基因表达的转录因子？4)HoE是 呼吸道合胞病毒感染激活p42/44激酶？这些观察结果很可能会 对呼吸道疾病的发病机制有重要的临床意义 接触粉尘的呼吸道合胞病毒感染儿童的炎症反应 含有内毒素。这些观察也可能暗示了一种相互作用 在病毒感染和各种环境暴露之间 呼吸道炎症的发病机制，可能还有哮喘。

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness in children. The primary site of RSV infection is the airway epithelium and it is associated with a predominance of neutrophils in bronchoalveolar lavage fluid. The presence of neutrophils in the airways is paralleled by increased amounts of IL-8, a potent chemotactic factor for neutrophils. An interesting clinical feature of RSV infection is that it is followed by an increase in airway reactivity. Relevant to this program, this increased airway reactivity includes a greater response to endotoxin-containing dusts. In our preliminary studies, we found that airway epithelium does not respond to endotoxin by releasing IL-8. If the epithelium is infected with RSV, however, there is a marked increased in the release of IL-8 when endotoxin is added to the monolayers. Based on these observations, we hypothesized that RSV infection up-regulates the response of airway epithelium to endotoxin. Since we cannot study all of the relevant mechanisms as they relate to this hypothesis, we decided to ask the following questions: 1) Does RSV infection up-regulate the response to endotoxin in airway epithelium? 2) Does the RSV-induced response to endotoxin result in upregulation of critical mitogen-activated protein kinase (MAPK) pathways? 3) Is the activation of these MAPK pathways linked to the activation of specific transcription factors that regulate IL-8 gene expression? 4) Hoe is the p42/44 kinase activated by RSV infection? These observations are likely to have important clinical implications for the pathogenesis of airway inflammation in children who have RSV infections and are exposed to dusts containing endotoxin. These observations also might suggest an interaction between viral infections and a variety of environmental exposures in the pathogenesis of airway inflammation and, possibly, asthma.