INTERLEUKIN 13

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 严重哮喘占哮喘人口的一小部分，但费用昂贵，难以治疗。对其发病机制知之甚少。一些证据表明，严重哮喘患者可能失去了肺的一些弹性特性，使呼吸道容易崩溃。这与肺气肿患者的情况相似，但导致这两种疾病的炎症过程似乎截然不同。来自我们实验室的初步数据表明，严重哮喘患者的肺有证据表明弹性蛋白发生了变化，弹性蛋白是一种有助于肺的弹性特性的蛋白质，类似于肺气肿的情况。这些改变似乎在小气道和肺泡(气囊)附着处最为明显。此外，肌成纤维细胞是愈合伤口中的重要细胞，在严重哮喘中似乎也增加了，但同样，主要是在肺的远端。细胞因子白介素13可能通过上调一种名为基质金属蛋白酶12的蛋白质来调节其中一些变化，该蛋白质已被发现与肺气肿模型有关。我们建议通过经支气管活检和支气管肺泡灌洗来研究不同严重程度的哮喘患者的肺远端部分，以评估IL-13、肌成纤维细胞、弹性蛋白和肺弹性丧失的差异。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Severe asthma makes up a small, but expensive and difficult to treat portion of the asthma population. Little is known about its pathogenesis. Some evidence suggests that severe asthmatics may have lost some of the elastic properties of their lungs, predisposing the airways to collapse. This is similar to what occurs in people with emphysema, yet the inflammatory processes that drive the two diseases appear to be quite different. Preliminary data from our laboratory suggest that the lungs from patients with severe asthma have evidence for changes in elastin, a protein that contributes to elastic properties of the lungs, that are similar to those seen in emphysema. These changes appear to be most prominent in the small airways and alveolar (air sac) attachments. Additionally, myofibroblasts, cells that are prominent in healing wounds, also appear to be increased in severe asthma, but again, primarily in the distal portion of the lung. The cytokine, interleukin 13 may play a role in modulating some of these changes by up-regulating a protein, matrix metalloproteinase 12, which has been found in association with models of emphysema. We propose to study the distal portion of the lungs through transbronchial biopsies and bronchoalveolar lavage, in patients with a wide range of asthma severity, to evaluate the differences in IL-13, myofibroblasts, elastin and the loss of elasticity of the lungs.