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01-07-2007 | ORIGINAL PAPER

The ICE Inhibitor Pralnacasan Prevents DSS-Induced Colitis in C57BL/6 Mice and Suppresses IP-10 mRNA but Not TNF-α mRNA Expression

Authors: Christian Bauer, Florian Loher, Marc Dauer, Christine Mayer, Hans Anton Lehr, Martin Schönharting, Roland Hallwachs, Stefan Endres, Andreas Eigler

Published in: Digestive Diseases and Sciences | Issue 7/2007

Abstract

Previously we demonstrated an ameliorating effect of the interleukin-1ß converting enzyme (ICE) inhibitor pralnacasan on dextran sulfate sodium (DSS)-induced colitis. This study investigates the effects of pralnacasan on cytokine expression in DSS-induced colitis. Colitis was induced by oral administration of DSS. Mice were treated intraperitoneally with the ICE inhibitor pralnacasan (50 mg/kg body weight twice daily). Body weight as well as the presence of occult blood or diarrhea was monitored daily. Subgroups were sacrificed at days 4, 8, and 11 after the beginning of DSS application. Cytokine profiles in colonic tissue were analyzed on the protein level by ELISA and on the mRNA level by real time RT-PCR. Administration of DSS led to an increase in IL-18, IL-12, TNF-α, and IFN-γ protein as well as IP-10 and TNF-α mRNA. The increase in IL-18 and IFN-γ was reduced by ICE inhibition. Pralnacasan prevented DSS-induced colitis in C57BL/6 mice. In C57BL/6 mice, the DSS-induced increase in IP-10 mRNA, but not TNF-α mRNA, was completely prevented by ICE inhibition. In conclusion, prevention of colitis in C57BL/6 mice was associated with a suppresion of IP-10 mRNA, but not TNF-α mRNA expression, indicating that IL-18-mediated cytokine production is a key element in the pathogenesis of DSS-induced colitis.

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Title: The ICE Inhibitor Pralnacasan Prevents DSS-Induced Colitis in C57BL/6 Mice and Suppresses IP-10 mRNA but Not TNF-α mRNA Expression
Authors: Christian Bauer
Florian Loher
Marc Dauer
Christine Mayer
Hans Anton Lehr
Martin Schönharting
Roland Hallwachs
Stefan Endres
Andreas Eigler
Publication date: 01-07-2007
Publisher: Kluwer Academic Publishers-Plenum Publishers
Published in: Digestive Diseases and Sciences / Issue 7/2007
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-007-9802-8

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