TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk.
PF Piguet, C Vesin, Y Donati… - Laboratory investigation; a …, 1999 - europepmc.org
PF Piguet, C Vesin, Y Donati, C Barazzone
Laboratory investigation; a journal of technical methods and pathology, 1999•europepmc.orgInjection of mouse recombinant TNF to mice induced apoptosis and detachment of the
enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage
of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of
cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection.
Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce
apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 …
enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage
of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of
cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection.
Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce
apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 …
Injection of mouse recombinant TNF to mice induced apoptosis and detachment of the enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection. Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 microg) decreased enterocyte detachment and apoptosis, as well as villus atrophy, whereas a caspase 3 inhibitor (Z-DEVD-cmk) had no effect. The results indicate that the induction of caspases by TNF is the cause of their detachment in the lumen and of the resulting villus atrophy.
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