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128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

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Impact of the specific JNK inhibitor D-JNK-1on acute and chronic colitis in a DSS mouse model

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  • Sabine Kersting - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Christoph Hilgert - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Volker Behrendt - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Jonas Kersting - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Monika Janot - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Dominique Sülberg - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Thomas Herdegen - Universitätsklinikum Schleswig-Holstein, Institut für Pharmakologie, Kiel
  • Waldemar Uhl - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum
  • Ansgar Chromik - St. Josef-Hospital, Klinik der Ruhr-Universität Bochum, Klinik für Allgemein- und Viszeralchirurgie, Bochum

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch075

doi: 10.3205/11dgch075, urn:nbn:de:0183-11dgch0751

Published: May 20, 2011

© 2011 Kersting et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

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Introduction: The c-Jun N-terminal kinase (JNK) is involved in maturation and activation of T cells and the synthesis of pro-inflammatory cytokines. Several studies demonstrated the relevance of the JNK pathway in inflammatory bowel diseases (IBD). Thus JNK inhibition may represent a potential therapy in IBD. The aim of this study was to investigate the impact of D-JNK-1, a specific JNK inhibitor, in a Dextran Sulfate Sodium (DSS) mouse model of mild acute and chronic colitis.

Materials and methods: DSS colitis was induced in female C57BL/6 mice. For acute colitis mice (n=30) received 1.5% DSS for 5 days. Half of the mice (n=15) were treated with D-JNK-1 s.c. on day 2, 4 and 6. Mice were sacrificed on day 7. Chronic colitis (n=30) was induced by cyclic administration of 1.5 % DSS (three cycles, each consisting of 5d DSS and 5d H2O). Half of the mice (n=15) were treated with D-JNK-1 s.c. on day 3, 13 and 23. Mice were sacrificed on day 30. The impact of D-JNK-1 on DSS colitis was examined by daily disease activity index (DAI), histological crypt damage score (CDS) and quantification of CD4 and CD8 cells by immunohistochemistry.

Results: Application of D-JNK-1 resulted in a significant decrease of DAI in acute (p=0.049) and chronic (p=0.013) DSS colitis. As only a mild colitis was induced, histological examination did not show distinct damage of mucosa and crypts. Thus a significant effect of D-JNK-1 on CDS could not be detected. However expression of CD4 and CD8 positive cells was reduced in mice treated with D-JNK-1 (not significant).

Conclusion: In conclusion, our data clearly demonstated the important role of the JNK pathway in acute and chronic IBD. Application of the specific JNK inhibitor D-JNK-1 resulted in a clinical attenuation of acute and chronic DSS colitis. The decrease of CD4 and CD8 cells reflects the influence of D-JNK-1 on T cell activation and migration.