Compressive forces stimulate release of TGFβ2 from differentiated bronchial epithelial cell cultures from asthmatic but not normal donors

Bronchoconstriction induces mechanical stress in the airways and normal bronchial epithelial cells respond by inducing profibrogenic responses. No studies have examined whether these responses are similar in asthmatic and non asthmatic populations. We tested the hypothesis that primary bronchial epithelial cells from asthmatic and non asthmatic donors respond similarly to mechanical stress mimicking bronchoconstriction by release of TGFβ2. Methods: Bronchial epithelial cells from healthy (n=9) and asthmatic (n=9) volunteers were obtained at bronchoscopy, expanded and grown at an air liquid interface (ALI). These were apically compressed with 5%CO 2 in air (30cm water pressure) for 1 hour, or sham compressed. 24 hours later total TGFβ2 was measured by ELISA in the basolateral medium. Results: After sham compression, TGFβ2 release was similar in ALI cultures from healthy (median (IQR) 203.4 (143.8-271.7) pg/ml) or asthmatic (245.5 (162.3-276.6)) donors (p=0.67). After active compression, TGFβ2 significantly increased in the asthmatic ALI culture medium (median (IQR) of 299.4 (205.4-365.0)) (p=0.02) but there was no increase in healthy cultures (median (IQR) 254.0 (137.7-281.7)) (p=0.68). This change amounted to a median (IQR) difference of 65.7 (24.5-110.7) pg/ml in the asthmatic group and 11.6 (-35.6-48.7) in the healthy group (p=0.04). Conclusions: Bronchial epithelial cells from asthmatic patients respond differently from normal cells to compressive force in vitro that mimics bronchoconstriction. This new finding suggests that there are at least two abnormalities in the asthmatic airway; the initial bronchoconstriction, and the epithelial response to it.