TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk.

Abstract

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.

• Authors: P F Piguet, C Vesin, Y Donati, C Barazzone
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 79 Issue 4 Pg. 495-500 (Apr 1999) ISSN: 0023-6837 [Print] United States
• PMID: 10212002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Antigens, CD
• Cysteine Proteinase Inhibitors
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Animals
• Antigens, CD (genetics, metabolism, physiology)
• Apoptosis (drug effects, physiology)
• Cell Adhesion (drug effects, physiology)
• Cysteine Proteinase Inhibitors (pharmacology)
• DNA Fragmentation
• Intestinal Mucosa (cytology, drug effects, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Inbred CBA
• Mice, Knockout
• Receptors, Tumor Necrosis Factor (genetics, metabolism, physiology)
• Receptors, Tumor Necrosis Factor, Type I
• Recombinant Proteins (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)