INTERLEUKIN 13

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 重度哮喘占哮喘人群的一小部分，但昂贵且难以治疗。 其发病机制知之甚少。 一些证据表明，严重的哮喘患者可能已经失去了肺部的一些弹性，使气道容易塌陷。 这与肺气肿患者发生的情况相似，但驱动这两种疾病的炎症过程似乎完全不同。 我们实验室的初步数据表明，严重哮喘患者的肺部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部弹性特性的蛋白质，与肺气肿中所见相似。 这些变化似乎在小气道和肺泡（气囊）附件中最为突出。 此外，肌成纤维细胞，在愈合伤口中突出的细胞，似乎也在严重哮喘中增加，但同样，主要在肺的远端部分。 细胞因子白细胞介素13可能通过上调基质金属蛋白酶12（已发现与肺气肿模型相关）在调节这些变化中发挥作用。 我们建议通过经支气管活检和支气管肺泡灌洗研究肺的远端部分，在广泛的哮喘严重程度的患者中，评估IL-13，肌成纤维细胞，弹性蛋白和肺弹性损失的差异。

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.