Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice.

Autor: Miller, Marina, Jae Youn Cho, McElwain, Kirsti, McElwain, Shauna, Jung Yeon Shim, Manni, Michael, Ji Sun Baek, Broide, David H.
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Zdroj: American Journal of Physiology: Lung Cellular & Molecular Physiology; Jan2006, Vol. 290, pL162-L169, 8p, 1 Diagram, 5 Graphs
Abstrakt: At present there are conflicting results from studies investigating the role of corticosteroids in inhibiting airway remodeling in asthma. We have used a mouse model to determine whether administration of corticosteroids prevents the development of allergen-induced structural features of airway remodeling, Mice treated with corticosteroids were subjected to repetitive ovalbumin (OVA) challenge for 3 mo, at which time levels of peribronchial fibrosis and the thickness of the peribronchial smooth muscle layer were assessed by immunohistology, levels of transforming growth factor (TGF)-β1 by ELISA, and the number of α-smooth muscle actin+/Col-1+ peribronchial myofibroblasts by immunohistochemistry. Corticosteroids significantly reduced allergen-induced increases in peribronchial collagen deposition and levels of total lung collagen but did not reduce allergen-induced increases in the thickness of the peribronchial smooth muscle layer. Levels of lung TGF-β1 were significantly reduced in mice treated with systemic corticosteroids, and this was associated with a significant decrease in the number of peribronchial inflammatory cells that expressed TGF-β1, including eosinophils and mononuclear cells. Corticosteroids also significantly reduced the number of peribronchial myofibroblasts. Overall, these studies demonstrate that administration of corticosteroids significantly reduces levels of allergen-induced peribronchial fibrosis. The reduction in peribronchial fibrosis mediated by corticosteroids is likely to be due to several mechanisms including inhibition of expression of TGF-β1, a reduction in the number of peribronchial inflammatory cells expressing TGF-β1 (eosinophils, macrophages), as well as by corticosteroids reducing the accumulation of peribronchial myofibroblasts that contribute to collagen expression. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index