TGF-beta isoform release and activation during in vitro bronchial epithelial wound repair.
Restitution of an epithelial layer after environmental or biological damage is important to maintain the normal function of the respiratory tract. We have investigated the role of transforming growth factor (TGF)-beta isoforms in the repair of layers of 16HBE 14o(-) bronchial epithelial-derived cells after damage by multiple scoring. ELISA showed that both latent TGF-beta1 and TGF-beta2 were converted to their active forms 2 h after wounding. Time-lapse microscopy showed that the addition of TGF-beta1, but not TGF-beta2, progressively increased the rate of migration of damaged monolayers at concentrations down to 250 pg/ml. This increase was blocked by addition of a neutralizing TGF-beta1 antibody. Phase-contrast microscopy and inhibition of proliferation with mitomycin C showed that proliferation was not required for migration. These results demonstrate that conversion of latent to active TGF-beta1 and TGF-beta2 during in vitro epithelial wound repair occurs quickly and that TGF-beta1 speeds epithelial repair. A faster repair may be advantageous in preventing access of environmental agents to the internal milieu of the lung although the production of active TGF-beta molecules may augment subepithelial fibrosis.
Howat
William J
WJ
Division of Respiratory, Cell and Molecular Biology, School of Medicine, University of Southampton, United Kingdom. W.J.Howat@soton.ac.uk
Holgate
Stephen T
ST
Lackie
Peter M
PM
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001980:Bronchi / Q000293:injuries*; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004848:Epithelium / Q000293:injuries; D020033:Protein Isoforms / Q000494:pharmacology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D014945:Wound Healing / Q000502:physiology*
D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2