Molecular biologic approach for chronic and irractable asthma-analysis for mechanism of remodeling using murine asthmatic model

由于气道重塑发生在过敏性炎症的治疗过程中，并被认为与哮喘的不稳定性有关，因此控制气道重塑成为近年来研究的重要课题。在巨噬细胞产生的细胞因子中，PDGF是成纤维细胞的竞争因子。本研究采用小鼠哮喘模型，研究巨噬细胞相关的哮喘气道重塑对肺组织生长因子和转化生长因子-β的影响，以及细胞因子的中和对哮喘气道重塑的治疗作用。暴露于油烟废气颗粒物2周后，呼吸道对乙酰胆碱的反应性升高。在呼吸道部位，激活的吞噬细胞增多，上皮细胞损伤，Clara细胞增多，基底膜下胶原沉积。联合应用抗血小板衍生生长因子中和抗体和转化生长因子-β中和抗体可抑制大鼠的气道壁增厚。通过给予抗转化生长因子-β和而不是PDGF中和抗体，由过敏原暴露引起的气道重塑被减轻。这些结果表明，中和血小板衍生生长因子和转化生长因子-β将控制哮喘的气道重塑。

Because the remodeling of airway is taken place in the process of cure from the allergic inflammation, and is thought to be related to irractablility of asthma, it become to consider important to control airway remodeling recently. Among the cytokine produced by macrophages, PDGF is comopetence factor of fibroblasts. We investigated which extent PFGF and TGF-β produced by macrophage related airway remdodeling of asthma, and the neutralization of the cytokine cure the airway remodeling using mice asthmatic model. The exposure of dieasel exhaust particulate for two weeks resulted in airway hypreresponsivenss to acethylcholine. At the site of the airway, the increase of activated and phagocytic macrophage, epithelial cell damage, increase of clara cells, and collagen deposition beneath basement membrane. The airway wall thickening was inhibited by the administration of anti-PDGF and TGF-β neutralizing antibody with DEP exposure. By the administration of anti-TGF-β and but not PDGF neutralizing antibody, airway remodeling caused by allergen exposure is diminished. These results indicated that neutralization of PDGF and TGF-β will control airway remodeling of asthma.