Epidermal growth factor attenuates Clostridium difficile toxin A- and B-induced damage of human colonic mucosa.
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(-6) M) 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.
Riegler
M
M
University Clinic of Surgery, University of Vienna, Austria.
Sedivy
R
R
Sogukoglu
T
T
Castagliuolo
I
I
Pothoulakis
C
C
Cosentini
E
E
Bischof
G
G
Hamilton
G
G
Teleky
B
B
Feil
W
W
Lamont
J T
JT
Wenzl
E
E
D000199:Actins / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002478:Cells, Cultured; D016360:Clostridioides difficile; D003106:Colon; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007082:Ileum; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D009336:Necrosis; D051381:Rats
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D004815:Epidermal Growth Factor; D019833:Genistein