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

由于气道重塑是在过敏性炎症的治疗过程中发生的，并且被认为与哮喘的难治性有关，因此控制气道重塑成为近年来人们关注的重要问题。巨噬细胞产生的细胞因子中，PDGF是成纤维细胞的能力因子。我们利用小鼠哮喘模型研究巨噬细胞产生的PFGF和TGF-β在多大程度上与哮喘气道重塑相关，以及细胞因子的中和对气道重塑的治疗作用。柴油机废气颗粒暴露两周后，气道对乙酰胆碱高反应。气道部位活化和吞噬性巨噬细胞增多，上皮细胞损伤，clara细胞增多，基底膜下胶原沉积。DEP暴露后，抗pdgf和TGF-β中和抗体可抑制气道壁增厚。通过给予抗tgf -β抗体，而不给予PDGF中和抗体，可减轻过敏原暴露引起的气道重塑。上述结果提示PDGF和TGF-β的中和可控制哮喘气道重塑。

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.