HUMAN BRONCHIAL EPITHELIAL-CELLS MODULATE COLLAGEN GEL CONTRACTION BYFIBROBLASTS

Connective tissue contraction is an important aspect of both normal wo und healing and fibrosis. This process may contribute to small airway narrowing associated with certain airway diseases. Fibroblast-mediated contraction of a three-dimensional collagen gel has been considered a model of tissue contraction. In this study, the ability of primary cu ltured human bronchial epithelial cells (HBEC) obtained by bronchial b rushings to modulate fibroblast gel contraction was evaluated. Human l ung fibroblasts (HFL1) were cast into type I collagen gels. The gels w ere floated both in dishes containing a monolayer of HBEC or in dishes without HBEC. Contraction assessed by measuring the area of gels was increased at all time points from 24 h up to 96 h of coculture. At 48 h, coculture of HBEC with fibroblasts resulted in significantly more c ontraction than fibroblasts alone (36.6 +/- 1.2 vs. 20.4 +/- 1.7%, P < 0.05). Lipopolysaccharide (LPS, 10 mu g/ml) stimulation of the HBEC a ugmented the contraction (44.9 +/- 1.0%, P < 0.05 vs. HBEC). In the pr esence of indomethacin, the augmentation by LPS was increased further (52.2 +/- 4.3%, P < 0.05 vs. HBEC with LPS), suggesting that prostagla ndins (PGs) are present and may inhibit contraction. Consistent with t his, PGE was present in HBEC-conditioned medium. Bronchial epithelial cell conditioned medium had an effect similar to coculturing. SG-150 c olumn chromatography revealed augmentive activity between 20 and 30 kD a and inhibitory activity between 10 and 20 kDa. Measurement by enzyme -linked immunosorbent assay confirmed the presence of the active form of transforming growth factor (TGF)-beta(2). The stimulatory activity of conditioned medium was blocked by adding anti-TGF-beta antibody. Th ese data demonstrate that, through the release of factors including TG F-beta(2) which can augment and PGE which can inhibit, HBEC can modula te fibroblast-mediated collagen gel contraction. In this manner, HBEC may modulate fibroblast activities that determine the architecture of bronchial tissue.