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.