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

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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.