中文摘要
IgE介导的食物过敏反应中钙离子作为经典信号通路的交汇点,在肥大细胞过敏反应中发挥“第二信使”的作用。前期研究发现机体受到感染后坏死细胞释放了细胞内钙离子而增加了细胞外钙离子水平,同时加剧了IgE介导的食物过敏反应中肥大细胞的激活,包括脱颗粒,TH2型和炎症相关细胞因子产生等。此过程可能激活了细胞膜上可以感应钙离子的钙敏感受体而加剧肥大细胞的激活。钙敏感受体在心血管疾病和免疫性疾病等多种疾病中都发挥重要的作用,而尚无钙敏感受体在食物过敏方面的报道。本研究中,我们利用动物模型和细胞模型确定肥大细胞上钙敏感受体在IgE介导的食物过敏反应中的作用,从蛋白质生物结构学和信号转导途径等方面深入研究钙敏感受体与细胞外钙内流的关系,并结合DNA微阵列完善钙敏感受体参与IgE介导的食物过敏反应肥大细胞激活的分子机制,阐明钙-钙敏感受体-IgE介导的食物过敏之间的重要联系,为治疗食物过敏性疾病奠定研究基础。
英文摘要
In the mechanism of IgE-mediated food allergy, calcium ion—the intersection of many classical signal pathways plays a “second messenger” role on mast cells. In our previous research, we found that extracellular calcium ion released from the necrotic cell after inflection can significantly aggravate the activation of mast cells in the food allergy, including degranulation and the production of TH2 and inflammation cytokines. Thus, we speculate that the increased extracellular calcium ion may active calcium sensing receptor which can sense the calcium ion to aggravate the activation of mast cells. Now many studies have reported the crucial effect of calcium sensing receptor in a variety of diseases, such as angiocardiopathy, immune diseases and so on. However, no studies on the calcium sensing receptor in the IgE-mediated food allergy have been reported. In this research, we will study the effect and mechanism of calcium sensing receptor, which expresses on the surface of mast cells on the activation of mast cells in the IgE-mediated food allergy using Balb/c mice food allergy model and cellular immunology model and explore the relationship between calcium sensing receptor and extracellular calcium ion influx from the structural biology and signal transduction pathway and the molecule mechanism using DNA microarray to elucidate the key association among calcium, calcium sensing receptor and IgE-mediated food allergy which can be used to relieve the sufferings of allergic patients.
