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Am J Physiol Lung Cell Mol Physiol 274: L119-L126, 1998;
1040-0605/98 $5.00
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Vol. 274, Issue 1, L119-L126, January 1998

Human bronchial epithelial cells modulate collagen gel contraction by fibroblasts

Tadashi Mio1, Xiang-Der Liu2, Yuichi Adachi3, Ilja Striz4, C. Magnus Sköld2, Debra J. Romberger2, John R. Spurzem2, Mary G. Illig2, Ron Ertl2, and Stephen I. Rennard2

1 Pulmonary Medicine, Chest Disease Research Institute, Kyoto University, Kyoto 601; 3 Department of Pediatrics, Toyama Medical and Pharmaceutical University, Toyama 930-01, Japan; 2 Pulmonary and Critical Care Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5300; and 4 Department of Immunology, Institute of Clinical and Experimental Medicine, 140 00 Prague 4, Czech Republic

Connective tissue contraction is an important aspect of both normal wound 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 cultured human bronchial epithelial cells (HBEC) obtained by bronchial brushings to modulate fibroblast gel contraction was evaluated. Human lung fibroblasts (HFL1) were cast into type I collagen gels. The gels were 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 contraction than fibroblasts alone (36.6 ± 1.2 vs. 20.4 ± 1.7%, P < 0.05). Lipopolysaccharide (LPS, 10 µg/ml) stimulation of the HBEC augmented the contraction (44.9 ± 1.0%, P < 0.05 vs. HBEC). In the presence of indomethacin, the augmentation by LPS was increased further (52.2 ± 4.3%, P < 0.05 vs. HBEC with LPS), suggesting that prostaglandins (PGs) are present and may inhibit contraction. Consistent with this, PGE was present in HBEC-conditioned medium. Bronchial epithelial cell conditioned medium had an effect similar to coculturing. SG-150 column chromatography revealed augmentive activity between 20 and 30 kDa 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. These data demonstrate that, through the release of factors including TGF-beta 2 which can augment and PGE which can inhibit, HBEC can modulate fibroblast-mediated collagen gel contraction. In this manner, HBEC may modulate fibroblast activities that determine the architecture of bronchial tissue.

remodeling; transforming growth factor-beta


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