title: Coexposure to environmental tobacco smoke increases levels of allergen-induced airway remodeling in mice.
abstract: Environmental tobacco smoke (ETS) can increase asthma symptoms and the frequency of asthma attacks. However, the contribution of ETS to airway remodeling in asthma is at present unknown. In this study, we have used a mouse model of allergen-induced airway remodeling to determine whether the combination of chronic exposure to ETS and chronic exposure to OVA allergen induces greater levels of airway remodeling than exposure to either chronic ETS or chronic OVA allergen alone. Mice exposed to chronic ETS alone did not develop significant eosinophilic airway inflammation, airway remodeling, or increased airway hyperreactivity to methacholine. In contrast, mice exposed to chronic OVA allergen had significantly increased levels of peribronchial fibrosis, increased thickening of the smooth muscle layer, increased mucus, and increased airway hyperreactivity which was significantly enhanced by coexposure to the combination of chronic ETS and chronic OVA allergen. Mice coexposed to chronic ETS and chronic OVA allergen had significantly increased levels of eotaxin-1 expression in airway epithelium which was associated with increased numbers of peribronchial eosinophils, as well as increased numbers of peribronchial cells expressing TGF-beta1. These studies suggest that chronic coexposure to ETS significantly increases levels of allergen-induced airway remodeling (in particular smooth muscle thickness) and airway responsiveness by up-regulating expression of chemokines such as eotaxin-1 in airway epithelium with resultant recruitment of cells expressing TGF-beta1 to the airway and enhanced airway remodeling.
authors.affiliation: Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA.
authors.forename: Myung Goo
authors.initials: MG
authors.lastname: Min
authors.forename: Dae Jin
authors.initials: DJ
authors.lastname: Song
authors.forename: Marina
authors.initials: M
authors.lastname: Miller
authors.forename: Jae Youn
authors.initials: JY
authors.lastname: Cho
authors.forename: Shauna
authors.initials: S
authors.lastname: McElwain
authors.forename: Paul
authors.initials: P
authors.lastname: Ferguson
authors.forename: David H
authors.initials: DH
authors.lastname: Broide
mesh_terms: D000199:Actins / Q000032:analysis; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000473:pathology*; D016535:Bronchial Hyperreactivity / Q000209:etiology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor; D004802:Eosinophilia / Q000209:etiology; D017874:Immediate-Early Proteins / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009093:Mucus / Q000378:metabolism; D009130:Muscle, Smooth / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000032:analysis
chemical_list: D000199:Actins; D000485:Allergens; C526318:CCN2 protein, mouse; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015848:Interleukin-5; D014028:Tobacco Smoke Pollution; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D010047:Ovalbumin; D003094:Collagen