Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice
Autor: | Jae Youn Cho, David H. Broide, Shauna McElwain, Michael Manni, Kirsti McElwain, Jung Yeon Shim, Marina Miller, Ji Sun Baek |
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Rok vydání: | 2006 |
Předmět: |
Pulmonary and Respiratory Medicine
Allergy Ovalbumin Physiology Myocytes Smooth Muscle Bronchi Biology Transforming Growth Factor beta1 Mice Adrenal Cortex Hormones Transforming Growth Factor beta Physiology (medical) Hypersensitivity medicine Animals Bronchitis Lung Asthma Mice Inbred BALB C Staining and Labeling Muscle Smooth Cell Biology Fibroblasts respiratory system Eosinophil medicine.disease Actins Fibronectins Mucus medicine.anatomical_structure Immunology Immunologic Techniques Collagen Airway Myofibroblast |
Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 290:L162-L169 |
ISSN: | 1522-1504 1040-0605 |
Popis: | 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)-beta1 by ELISA, and the number of alpha-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-beta1 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-beta1, 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-beta1, a reduction in the number of peribronchial inflammatory cells expressing TGF-beta1 (eosinophils, macrophages), as well as by corticosteroids reducing the accumulation of peribronchial myofibroblasts that contribute to collagen expression. |
Databáze: | OpenAIRE |
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