Expression and activation of TGF-beta isoforms in acute allergen-induced remodelling in asthma.
BACKGROUND
Airway wall remodelling and inflammation are features of chronic asthma. Transforming growth factor beta (TGF-beta) has been implicated in these processes.


OBJECTIVE
To determine the effect of allergen challenge on airway inflammation and remodelling and whether TGF-beta 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 (FEV(1)) 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-beta isoforms 1, 2 and 3 were expressed predominantly in bronchial epithelium after saline and allergen challenges, but only TGF-beta(2) expression was increased after allergen. Double immunostaining showed an increase in TGF-beta(2) positive eosinophils and neutrophils but not in TGF-beta(1) positive eosinophils and neutrophils after allergen challenge.


CONCLUSIONS
TGF-beta(2) may contribute to the remodelling changes in allergic asthma following single allergen exposure.
Torrego
Alfons
A
National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK.
Hew
Mark
M
Oates
Tim
T
Sukkar
Maria
M
Fan Chung
Kian
K
D000328:Adult; D000485:Allergens / Q000009:adverse effects*; D001249:Asthma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001706:Biopsy / Q000379:methods; D001980:Bronchi / Q000473:pathology; D001991:Bronchitis / Q000473:pathology; D001999:Bronchoscopy / Q000379:methods; D002908:Chronic Disease; D004804:Eosinophils / Q000473:pathology; D005336:Fiber Optic Technology; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D009504:Neutrophils / Q000473:pathology; D020545:Respiratory Mucosa / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000485:Allergens; D016212:Transforming Growth Factor beta