BRONCHIAL EPITHELIAL-CELLS REGULATE FIBROBLAST PROLIFERATION

Chronic bronchitis frequently leads to irreversible airway obstruction . Alteration of airway architecture with abnormal airway connective ti ssue is thought to play an important role in this process. We hypothes ized that the epithelial cells that line the airways modulate the deve lopment of peribronchial fibrosis and fixed airway obstruction by dire cting fibroblast proliferation. To assess this, we examined stimulator y activities for human lung fibroblast proliferation in bovine bronchi al epithelial cell-conditioned medium. The conditioned medium stimulat ed the proliferation of fibroblasts in a serum-free culture system in a concentration-dependent manner. The fibroblast growth stimulatory ac tivity was heterogenous, with molecular masses of > 50 and similar to 10 kDa. Bronchial epithelial cell-conditioned medium also contained fi broblast growth inhibitory factors, including both transforming growth factor (TGF)-beta and, based on indomethacin sensitivity, cyclooxygen ase products. TGF-beta appeared to contribute to the morphological cha nge of fibroblasts induced by the conditioned medium. Go-culture of hu man lung fibroblasts with bronchial epithelial cells resulted in a sti mulation of fibroblast proliferation. In summary, airway epithelial ce lls appear to regulate fibroblast proliferation and may play a role in peribronchial fibrosis in chronic bronchitis.