title: Corticosteroids prevent myofibroblast accumulation and airway remodeling in mice.
abstract: 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.
authors.affiliation: Department of Medicine, University of California San Diego, CA 92093-0635, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Kirsti
authors.initials: K
authors.lastname: McElwain
authors.forename: Shauna
authors.initials: S
authors.lastname: McElwain
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Shim
authors.forename: Michael
authors.initials: M
authors.lastname: Manni
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Baek
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
mesh_terms: D000199:Actins / Q000378:metabolism; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001991:Bronchitis / Q000473:pathology; D003094:Collagen / Q000037:antagonists & inhibitors / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology*; D005353:Fibronectins / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007158:Immunologic Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000473:pathology*; D010047:Ovalbumin / Q000276:immunology; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1
chemical_list: D000199:Actins; D000305:Adrenal Cortex Hormones; D005353:Fibronectins; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D010047:Ovalbumin; D003094:Collagen