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Expression and activation of TGF-β isoforms in acute allergen-induced remodelling in asthma
  1. Kian Fan Chung (f.chung{at}ic.ac.uk)
  1. National Heart & Lung Institute, United Kingdom
    1. Alfons Torrego (a.torrego{at}imperial.ac.uk)
    1. National Heart & Lung Institute, United Kingdom
      1. Mark Hew (m.hew{at}imperial.ac.uk)
      1. National Heart & Lung Institute, United Kingdom
        1. Maria Sukkar (m.sukkar{at}imperial.ac.uk)
        1. National Heart & Lung Institute, United Kingdom
          1. Tim Oates (t.oates{at}imperial.ac.uk)
          1. National Heart & Lung Institute, United Kingdom

            Abstract

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

            Objectives: We determined the effect of allergen challenge on airway inflammation and remodelling and whether TGF-β isoforms and the Smad signalling pathways were involved.

            Methods: Thirteen atopic asthmatics underwent inhalational challenge with 0.9% saline (SC), followed by allergen (AC) 3-4 weeks later. After both challenges, fiberoptic bronchoscopy was undertaken in order to obtain bronchial biopsies and tissue samples were processed for immunohistochemistry and examined by microscopy.

            Results: FEV1 fell after AC (-28.1 % ± 0.92, mean ± SEM, at 30 minutes) with a late response at 7 hours (-23.0% ± 1.23). AC caused an increase in neutrophils (p=0.016) and eosinophils (p=0.01) in the bronchial mucosa when compared with SC. Sub-basement membrane (SBM) thickness did not change after AC, but tenascin deposition in SBM was increased (p=0.02). Intranuclear (activated) Smad 2/3 and Smad 4 detected by immunohistochemistry were increased after AC 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 both after saline or allergen, but only TGF-β2 expression was increased after AC (p=0.03). Using double- immunostaining, an increase in TGF-β2-positive eosinophils (p=0.01) and neutrophils (p=0.04), but not in TGF-β1 positive eosinophils and neutrophils, was also found after AC.

            Conclusions: TGF-â2 may contribute to the remodelling changes in allergic asthma following single allergen exposure; further detailed studies will be needed.

            • TGFbeta
            • airway wall remodelling
            • allergen challenge
            • eosinophils

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