ASTHMA

Expression and activation of TGF-ß isoforms in acute allergen-induced remodelling in asthma

Alfons Torrego, Mark Hew, Tim Oates, Maria Sukkar, Kian Fan Chung

Airway Disease Section, National Heart and Lung Institute, Imperial College and Royal Brompton and Harefield NHS Trust, London, UK

Correspondence to:
Professor Kian Fan Chung
National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK; f.chung{at}imperial.ac.uk

Background: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor ß (TGF-ß) has been implicated in these processes.

Aim: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-ß isoforms and the Smad signalling pathways are involved.

Methods: Thirteen patients with atopic asthma underwent inhalational challenge with 0.9% saline, followed by allergen 3–4 weeks later. After both challenges, fibreoptic bronchoscopy was undertaken to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy.

Results: Forced expiratory volume in 1 s (FEV₁) fell after allergen challenge (mean (SE) –28.1 (0.9)% at 30 min with a late response at 7 hours (–23.0 (1.2)%). Allergen challenge caused an increase in neutrophils and eosinophils in the bronchial mucosa compared with saline. Sub-basement membrane (SBM) thickness did not change after allergen, but tenascin deposition in SBM was increased. Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after allergen challenge in epithelial and subepithelial cells of bronchial biopsies. No inhibitory Smad (Smad 7) protein was detected. TGF-ß isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-ß₂ expression was increased after allergen. Double immunostaining showed an increase in TGF-ß₂ positive eosinophils and neutrophils but not in TGF-ß₁ positive eosinophils and neutrophils after allergen challenge.

Conclusions: TGF-ß₂ may contribute to the remodelling changes in allergic asthma following single allergen exposure.

Abbreviations: FEV₁, forced expiratory volume in 1 s; MBP, major basic protein; NE, neutrophil elastase; SBM, sub-basement membrane; TGF-ß, transforming growth factor-ß

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