Expression of transforming growth factor-beta (TGF-beta) in chronic idiopathic cough.
In patients with chronic idiopathic cough, there is a chronic inflammatory response together with evidence of airway wall remodelling and an increase in airway epithelial nerves expressing TRPV-1. We hypothesised that these changes could result from an increase in growth factors such as TGFbeta and neurotrophins. We recruited 13 patients with persistent non-asthmatic cough despite specific treatment of associated primary cause(s), or without associated primary cause, and 19 normal non-coughing volunteers without cough as controls, who underwent fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsies. There was a significant increase in the levels of TGFbeta in BAL fluid, but not of nerve growth factor(NGF) and brain-derived nerve growth factor(BDNF) compared to normal volunteers. Levels of TFGbeta gene and protein expression were assessed in bronchial biopsies. mRNA expression for TGFbeta was observed in laser-captured airway smooth muscle and epithelial cells, and protein expression by immunohistochemistry was increased in ASM cells in chronic cough patients, associated with an increase in nuclear expression of the transcription factor, smad 2/3. Subbasement membrane thickness was significantly higher in cough patients compared to normal subjects and there was a positive correlation between TGF-beta levels in BAL and basement membrane thickening. TGFbeta in the airways may be important in the airway remodelling changes observed in chronic idiopathic cough patients, that could in turn lead to activation of the cough reflex.
Xie
Shaoping
S
Airway Disease Section, National Heart & Lung Institute, Imperial College & Royal Brompton Hospital, London SW3 6LY, UK. s.xie@imperial.ac.uk
Macedo
Patricia
P
Hew
Mark
M
Nassenstein
Christina
C
Lee
Kang-Yun
KY
Chung
Kian Fan
KF
D001706:Biopsy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000502:physiology; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D001999:Bronchoscopy; D002211:Capsaicin / Q000494:pharmacology; D002908:Chronic Disease; D003371:Cough / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism; D012907:Smoking / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D020932:Nerve Growth Factor; D002211:Capsaicin