TRANSFORMING GROWTH-FACTOR BETA(1) GENE-EXPRESSION IN HUMAN AIRWAYS

Background - Asthmatic airways have a characteristic deposition of con nective tissue under the epithelial basement membrane, but the mediato rs involved in this alteration are unknown. Several authors have postu lated that transforming growth factor beta(1) (TGF-beta(1)) could be o verexpressed in asthmatic airways. Methods - Lung samples from 16 asth matic patients, six patients with chronic obstructive pulmonary diseas e (COPD), and six non-obstructed smokers were analysed. RNA was extrac ted from these tissues to measure expression of TGF-beta(1) by Norther n blot analysis using a cDNA probe for TGF-beta(1). The level of expre ssion was quantitated by densitometry using glyceraldehyde 3-phosphate dehydrogenase mRNA as a control. TGF-beta(1), was localised to specif ic cell types in these lungs by immunohistochemical analysis using pol yclonal antibodies specific for intracellular and extracellular TGF-be ta(1). Results - The 2.5 kb TGF-beta(1) mRNA was seen in all 18 sample s analysed by Northern blotting and densitometric analysis showed no d ifference between the asthmatic group (mean (SD) 108% (43%)), the grou p with COPD (122% (33%)), and the non-obstructed group (100% (49%)). T he TGF-beta(1) precursor was immunolocalised throughout the airway wal l including the epithelium and in alveolar macrophages. The mature TGF -beta(1) was localised primarily within the connective tissue of the a irway wall. These patterns of expression of both forms of TGF-beta(1) were similar in lungs from asthmatic patients, those with COPD, and co ntrols. Conclusions - While TGF-beta(1) mRNA and protein are abundantl y expressed in human lungs, there is no clear difference in expression between the airways of asthmatic subjects and those of smokers with a nd without COPD.