Background: Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor β (TGF-β) has been implicated in these processes.
Aim: To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-β 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-β isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-β2 expression was increased after allergen. Double immunostaining showed an increase in TGF-β2 positive eosinophils and neutrophils but not in TGF-β1 positive eosinophils and neutrophils after allergen challenge.
Conclusions: TGF-β2 may contribute to the remodelling changes in allergic asthma following single allergen exposure.
- FEV1, forced expiratory volume in 1 s
- MBP, major basic protein
- NE, neutrophil elastase
- SBM, sub-basement membrane
- TGF-β, transforming growth factor-β
Statistics from Altmetric.com
Published Online First 24 January 2007
This study was supported by a Wellcome Trust grant and Dr Alfons Torrego was the recipient of a European Respiratory Society Fellowship.
Competing interests: None.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.