INTERLEUKIN-13, ACCUMULATION OF EXTRAVASCULAR FIBRIN AND AIRWAY CLOSURE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目旨在确定凝血系统在哮喘炎症环境中的作用。我们以前已经表明，血凝块的主要结构成分纤维蛋白不仅存在于哮喘患者的气道中，而且对于哮喘小鼠模型中气道高反应性的发展是足够和必要的。气道高反应性是哮喘的定义特征，被认为是哮喘患者气道持续炎症的结果。目前，我们正在努力将哮喘的炎症与气道内纤维蛋白的形成联系起来。白细胞介素-13是一种细胞因子，被认为是哮喘气道炎症的中心。IL-13具有许多作用，其中一些包括上调纤溶酶原激活物抑制剂1型（派-1）。派-1抑制纤维蛋白的分解，因此派-1水平的增加将促进气道表面上的凝块或纤维蛋白形成。我们先前已经表明，在哮喘小鼠模型中派-1活性水平增加。在这个项目中，我们希望将IL-13与派-1联系起来，建立中间步骤的重要性，并确定IL-13如何导致派-1活性增加并最终形成纤维蛋白。

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. This project aims to define the role of the coagulation system in the inflammatory milieu of asthma. We have previously shown that fibrin, the main structural component of a blood clot, is not only present in the airways of asthmatics but also sufficient and necessary for the development of airway hyperresponsiveness in a mouse model of asthma. Airway hyperresponsiveness is a defining feature of asthma and is thought to be the result of persistent inflammation in the airways of asthmatics. Currently we are striving to link the inflammation in asthma to the formation of fibrin within airways. Interleukin-13 is a cytokine that is thought to be central in the inflamed asthmatic airway. IL-13 has many effects some of which include upregulation of plasminogen activator inhibitor type-1 (PAI-1). PAI-1 inhibits the break down of fibrin and hence increased levels of PAI-1 will promote clot or fibrin formation on the airway surface. We had previously shown that in a mouse model of asthma PAI-1 activity levels are increased. In this project we hope to link IL-13 to PAI-1 and establish the importance of intermediary steps and define how IL-13 leads to increased PAI-1 activity and ultimately fibrin formation.