Prevention for allergic diseases by clarification of interaction between environmental chemicals and genes of eosinophil-related protein

为了通过阐明环境和基因之间的关系，提出针对变态反应性疾病的个性化预防方法，我们比较了哮喘和雪松花粉症患者和正常对照的嗜酸性粒细胞趋化因子受体(CCR)家族、嗜酸性粒细胞趋化因子-2/CCL24、嗜酸性粒细胞趋化因子-3/CCL26、单核细胞趋化蛋白-1(MCP-1、CCL2)基因的单核苷酸多态性(SNP)。我们发现，与对照组相比，哮喘和雪松花粉症患者CCR3基因的51C、CCL26基因的2497G和2563C以及MCP-1基因的2518G的频率显著增加。这些蛋白的血清水平与这些过敏性疾病的严重程度有显著的相关性。这些结果提示嗜酸性粒细胞相关蛋白在变态反应性疾病中的临床意义。接下来，我们开发了新的过敏预防方法，使用了结合了活性碳和无定形氧化铁的过滤系统，可以有效地去除柴油尾气颗粒物(DEP)。我们证明，过滤系统去除DEP可显著抑制过敏反应，如肺组织中嗜酸性粒细胞和中性粒细胞的渗入，肺部炎症，以及Der f致敏和刺激哮喘模型小鼠BALB/c的Der f特异性IgG1抗体水平的升高。因此，如果在我们的生活中尽早(例如，在我们的婴儿期)开始使用这种过滤系统，可能是最有效的防止过敏发展的方法。

To propose tailor-made preventive methods for allergic diseases by clarification between environment and genes, we compared single nucleotide polymorphisms (SNP) of genes of eosinophil-related protein, e.g., CC chemokine receptor (CCR) family, Eotaxin/CCL11, Eotaxin-2/CCL24, Eotaxin-3/CCL26, Monocyte chemoattractant protein -1 (MCP-1, CCL2) between patients with asthma or Japanese cedar pollinosis and controls. We recognized significantly higher frequencies of 51 C in CCR3 gene, 2497G and 2563C in CCL26 gene, and 2518G in MCP-1 gene in patients with asthma or Japanese cedar pollinosis as compared to controls. There were significant correlations between serum levels of those proteins and severity of those allergic diseases. These results suggest the clinical significance of those eosinophils-related proteins in allergic diseases. Next, we developed the novel preventive methods for allergy, using the filter system incorporating activated carbon and amorphous iron(hydr)oxide, which efficiently removes diesel exhaust particulate (DEP). We demonstrated that removal of DEP by the filter system produced significant inhibition of allergic responses, e. g, eosinophils and neutrophils infiltration into lung tissues, lung inflammation and elevated Der f specific IgGl antibody level in asthma model mice BALB/c, which were sensitized and stimulated with Der f. Therefore, this filter system might be the most effective to prevent allergy development, if its use were started in our life as early as possible (e.g. in our infancy).