Epithelial-mesenchymal interaction and insulin-like growth factors in hyperoxic lung injury

To investigate the role of epithelial-mesenchymal interaction on oxygen-ind uced lung injury, we used a coculture model with lung fibroblasts (FB) embe dded between 2 layers of collagen gel with and without human tracheobronchi al epithelial cells (HTBE), and studied the effect of hyperoxia on the dire cted migration of FB towards epithelial cells and proliferation of fetal lu ng FB. The expression of insulin-like growth factor (IGF)-I, -II, and -IIR mRNAs and proteins was studied In FB and HTBE cells cultured separately in 95% oxygen and 5% CO2 for 48 hours. There was a significant increase in dir ectional migration of FB in coculture with epithelial cells when exposed to 95% oxygen and 5% CO2 (P = .04 compared to cocultures without oxygen expos ure). Hyperoxia stimulated the proliferation of fibroblasts cocultured with HTBE cells (0.75 +/- 0.05 X 10(6) cells per well) as compared to control ( 0.47 +/- 0.03 X 10(6) cells per well; P = .01). This was inhibited by anti- IGF-I antibody (69 +/- 2% of hyperoxia alone; P = .002). Western blot showe d a significant increase in IGF-I protein in epithelial cells (P = .02). IG F-I mRNA was inn eased in HTBE cells after hyper oxia (P = .003). In conclu sion, HTBE cells modulate lung FB migration and proliferation in response t o hyperoxia exposure. This is mediated in part by IGF-I produced by epithel ial cells.