Airway smooth muscle control of mast cells in asthma

点击翻译按钮获取中文摘要

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.