Epidermal growth factor attenuatesClostridium difficiletoxin A- and B-induced damage of human colonic mucosa

Autor: Gerhard Hamilton, Roland Sedivy, G Bischof, Etienne Wenzl, Ignazio Castagliuolo, W Feil, Tacettin Sogukoglu, Martin Riegler, J. T. Lamont, Charalabos Pothoulakis, B Teleky, E. P. Cosentini
Rok vydání: 1997
Předmět:
Zdroj: American Journal of Physiology-Gastrointestinal and Liver Physiology. 273:G1014-G1022
ISSN: 1522-1547
0193-1857
DOI: 10.1152/ajpgi.1997.273.5.g1014
Popis: Epidermal growth factor (EGF) exhibits a cytoprotective effect on gastrointestinal epithelia via a receptor-mediated mechanism. We investigated the effect of EGF on Clostridium difficile toxin A (TxA)- and toxin B (TxB)-induced damage of human colon. Ussing-chambered colonic mucosa was exposed serosally to EGF before and during luminal exposure to TxA and TxB. Resistance was calculated from potential difference and short-circuit current. Epithelial damage was assessed by light microscopy and alteration of F-actin by fluoresceinated phalloidin. Luminal exposure of colonic strips to TxA and TxB caused a time- and dose-dependent decrease in electrical resistance, necrosis and dehiscence of colonocytes, and disruption and condensation of enterocyte F-actin. These effects were inhibited by prior, but not simultaneous, serosal application of EGF (20 nM). Administration of the tyrosine kinase inhibitor genistein (10−6M) inhibited the protective effects of EGF. We conclude that EGF protects against TxA and TxB probably by stabilizing the cytoskeleton, the main target of these toxins.
Databáze: OpenAIRE