Airway smooth muscle control of mast cells in asthma

大约12%的澳大利亚人患有哮喘，多达25%的儿童受到影响。因此，这对我们和我们的医疗体系来说是一个沉重的负担。目前，我们用皮质类固醇来治疗哮喘，以减少呼吸道炎症，否则炎症会导致气道增厚，平滑肌(ASM)数量增加，收缩太多，太容易。然而，还需要更多的研究。皮质类固醇有时会停止作用或产生不良副作用，特别是对儿童来说，但我们仍然无法阻止或治愈哮喘的发生。我们需要更多地了解导致哮喘特有的炎症模式的化学信号，以便治愈它并防止它的发展。近年来，与支气管炎和健康人相比，哮喘患者ASM层中称为肥大细胞(MC)的炎性细胞数量增多。MC释放介质，收缩呼吸道，诱导粘液分泌，促进进一步炎症。我们认为ASM细胞和MC之间的相互作用是导致哮喘患者呼吸道生理变化的核心因素。在哮喘患者中，我们已经确定了ASM增加释放的一种化学信息(IP10)，它吸引MC进入它。我们也有证据表明，来自没有哮喘的人的ASM释放了阻止IP10和类似的化学信息在MC上发挥作用的因子。这两个令人兴奋的发现表明哮喘的ASM是不同的。我们将调查为什么哮喘ASM会产生更多的IP10，并试图阻止我们认为具有非常特定作用的药物的每一个步骤。此外，我们还将确定非哮喘ASM释放的抑制IP10和类似化学信息发挥作用的因子。通过这项研究获得的额外知识可能会导致设计新的治疗方法来预防哮喘症状，而不会产生副作用，并导致预防哮喘发展的新策略，特别是在儿童中。

Around 12% of Australians are asthmatic, with up to 25% of children affected. Thus it is a significant burden for us and our healthcare system. Currently we treat asthma with corticosteroids to reduce airway inflammation, otherwise the inflammation leads to thickened airways with increased amounts of smooth muscle (ASM) that contracts too much and too easily. However more research is needed. Corticosteroids sometimes stop working or have unwanted side effects, especially for children, and we still cannot prevent asthma developing or cure it. We need to know more about the chemical signals which cause the pattern of inflammation that is specific for asthma in order to cure it and prevent it developing. Recently, inflammatory cells called mast cells (MC) have been found in increased numbers in the ASM layer of asthmatics compared with bronchitics or healthy people. MC release mediators that contract the airways, induce mucous secretion and promote further inflammation. We think the effects ASM cells and MC have on each other are central factors in causing physical changes to the airways of asthmatics. In asthmatics we have identified a chemical message (IP10) released in increased amounts by the ASM which attracts MC to it. We also have evidence that ASM from people without asthma release factors that prevent IP10 and similar chemical messages from working on MC. These two exciting findings demonstrate asthmatic ASM is different. We will investigate why asthmatic ASM produces more IP10 and try to prevent each of the steps we identify with drugs that have very specific actions. In addition, we will identify the factors released by non-asthmatic ASM that inhibit IP10 and similar chemical messages from working. The additional knowledge gained by this research may lead to the design of novel treatments to prevent asthma symptoms without side effects and lead to new strategies to prevent asthma developing, especially in children.