Airway smooth muscle control of mast cells in asthma

哮喘中气道平滑肌对肥大细胞的控制

• 批准号: nhmrc : 457457
• 负责人: A/Pr Janette Burgess
• 金额: $ 40.85万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/airway-smooth-muscle-cells-asthma/95585
• 关键词: Airway; smooth; muscle; control; mast

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.

大约12%的澳大利亚人患有哮喘，受影响的儿童高达25%。因此，这对我们和我们的医疗保健系统来说是一个沉重的负担。目前，我们用皮质类固醇治疗哮喘以减少气道炎症，否则炎症会导致气道增厚，平滑肌（ASM）量增加，收缩过多且过于容易。然而，还需要更多的研究。皮质类固醇有时会停止工作或产生不必要的副作用，特别是对儿童，我们仍然不能预防哮喘的发展或治愈它。我们需要更多地了解引起哮喘特异性炎症模式的化学信号，以治愈它并预防它的发展。近年来，在哮喘患者的肺动脉平滑肌层中发现肥大细胞（MC），其数量明显多于支气管炎患者或健康人。MC释放介质，收缩气道，诱导粘液分泌和促进进一步的炎症。我们认为ASM细胞和MC相互作用是引起哮喘患者气道物理变化的中心因素。在哮喘患者中，我们已经发现ASM释放的化学信息（IP10）增加，从而吸引MC。我们也有证据表明，来自非哮喘患者的ASM释放的因子阻止了IP10和类似的化学信息对MC起作用。这两个令人兴奋的发现表明哮喘性ASM是不同的。我们将研究为什么哮喘ASM产生更多的IP10，并试图阻止我们确定的具有非常具体作用的药物的每个步骤。此外，我们将确定非哮喘ASM释放的抑制IP10和类似化学信息工作的因子。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没有副作用，并导致预防哮喘发展的新策略，特别是在儿童中。