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

Background - Asthmatic airways have a characteristic deposition of connective tissue under the epithelial basement membrane, but the mediators involved in this alteration are unknown. Several authors have postulated that transforming growth factor beta(1) (TGF-beta(1)) could be overexpressed in asthmatic airways. Methods - Lung samples from 16 asthmatic patients, six patients with chronic obstructive pulmonary disease (COPD), and six non-obstructed smokers were analysed. RNA was extracted from these tissues to measure expression of TGF-beta(1) by Northern blot analysis using a cDNA probe for TGF-beta(1). The level of expression was quantitated by densitometry using glyceraldehyde 3-phosphate dehydrogenase mRNA as a control. TGF-beta(1), was localised to specific cell types in these lungs by immunohistochemical analysis using polyclonal antibodies specific for intracellular and extracellular TGF-beta(1). Results - The 2.5 kb TGF-beta(1) mRNA was seen in all 18 samples analysed by Northern blotting and densitometric analysis showed no difference between the asthmatic group (mean (SD) 108% (43%)), the group with COPD (122% (33%)), and the non-obstructed group (100% (49%)). The TGF-beta(1) precursor was immunolocalised throughout the airway wall including the epithelium and in alveolar macrophages. The mature TGF-beta(1) was localised primarily within the connective tissue of the airway wall. These patterns of expression of both forms of TGF-beta(1) were similar in lungs from asthmatic patients, those with COPD, and controls. Conclusions - While TGF-beta(1) mRNA and protein are abundantly expressed in human lungs, there is no clear difference in expression between the airways of asthmatic subjects and those of smokers with and without COPD.