Modulation of asthmatic airway inflammation by activation of epithelial proteinase activated receptors

儿童和成人感到哮喘的症状是因为他们的气道太容易关闭。我们已经发现了一种新的机制，健康的肺用来保持气道畅通。排列在气道上的上皮细胞释放一种酶，这种酶可以切割位于同一细胞上的另一种蛋白质的一小部分，这种蛋白质称为PAR受体。当这种情况发生时，上皮细胞从其下表面释放放松物质。放松物质保持呼吸道畅通。这项拨款申请旨在测试放松系统是否也能阻止气道炎症的发展。如果放松系统做到了这一点，我们就能够利用我们所掌握的知识，人工激活PAR受体，设计新型药物。这些药物比现有的哮喘药物更好，因为它们可以同时预防炎症和放松气道。这些药物也可以用于其他肺部疾病，如慢性支气管炎。

Children and adults feel the symptoms of asthma because their airways close up too easily. We have discovered a new mechanism that the healthy lung uses to keep airways open. The epithelial cells which line the airway release an enzyme that cuts of a small part of another protein, called a PAR receptor, that sits on the same cell. When this happens the epithelial cell releases relaxing substances from their lower surface. The relaxing substances keep the airways open. This grant application is designed to test whether the relaxing system also stops the airways from developing inflammation. If the relaxing system does this we will be able to use the knowlege we have that lets us activate the PAR receptors artificially to design new types of drugs. These drugs would be better than existing asthma drugs because they would prevent inflammation and relax the airways at the same time. These drugs could also be useful in other lung diseases such as chronic bronchitis.