Back to Browse Journals » Journal of Inflammation Research » Volume 6

The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium

Authors Kersting S, Behrendt V, Kersting J, Reinecke K, Hilgert C, Stricker I, Herdegen T, Janot MS, Uhl W, Chromik AM

Published Date May 2013 Volume 2013:6 Pages 71—81

DOI http://dx.doi.org/10.2147/JIR.S40092

Received 8 November 2012, Accepted 26 January 2013, Published 3 May 2013

Sabine Kersting,1* Volker Behrendt,1* Jonas Kersting,1 Kirstin Reinecke,3 Christoph Hilgert,1 Ingo Stricker,2 Thomas Herdegen,3 Monika S Janot,1 Waldemar Uhl,1 Ansgar M Chromik1

1Department of General and Visceral Surgery, St Josef Hospital, Ruhr University of Bochum, Bochum, Germany; 2Department of Pathology, Ruhr University of Bochum, Bochum, Germany; 3Institute of Experimental and Clinical Pharmacology, University Hospital of Schleswig-Holstein, Kiel, Germany

*The two authors Sabine Kersting and Volker Behrendt contributed equally to this work

Purpose: The c-Jun N-terminal kinases (JNK) are involved in the activation of T cells and the synthesis of proinflammatory cytokines. Several studies have established the relevance of the JNK pathway in inflammatory bowel diseases. The present study analyzed the therapeutic effect of D-JNKI-1, a specific JNK-inhibiting peptide, in a low-dose dextran sulfate sodium (DSS) model of chronic colitis.
Methods: DSS colitis was induced in female C57/BL6 mice by cyclic administration using different concentrations of DSS (1.0% and 1.5%). Mice in the intervention groups received subcutaneous administration of 1 µg/kg D-JNKI-1 on days 2, 12, and 22. They were monitored daily to assess the severity of colitis, body weight, stool consistency, and the occurrence of occult blood or gross rectal bleeding using evaluation of the disease activity index. The animals were sacrificed after 30 days, and the inflamed intestine was histologically evaluated using a crypt damage score. Immunohistochemical quantification of CD4+ and CD8+ cells was also carried out.
Results: Administration of 1 µg/kg D-JNKI-1 resulted in a significant decrease in the disease activity index (P = 0.013 for 1.0% DSS; P = 0.007 for 1.5% DSS). As a mild form of colitis was induced, histological examination did not show any distinct damage to the mucosa and crypts. However, expression of CD4+ and CD8+ cells was reduced in mice treated with D-JNKI-1 (not significant).
Conclusion: Administration of D-JNKI-1 resulted in a clinical attenuation of chronic DSS colitis, and a therapeutic effect of D-JNKI-1 must therefore be assumed. The decrease in CD4+ and CD8+ cells may reflect the influence of D-JNKI-1 on T-cell activation, differentiation, and migration.

Keywords: c-Jun N-terminal kinase inhibitor, dextran sulfate sodium colitis, inflammatory bowel diseases, T cell, D-JNKI-1

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Other article by this author:

Knockout of the c-Jun N-terminal Kinase 2 aggravates the development of mild chronic dextran sulfate sodium colitis independently of expression of intestinal cytokines TNFα, TGFB1, and IL-6

Kersting S, Reinecke K, Hilgert C, Janot MS, Haarmann E, Albrecht M, Müller AM, Herdegen T, Mittelkötter U, Uhl W, Chromik AM

Journal of Inflammation Research 2013, 6:13-23

Published Date: 12 February 2013

Readers of this article also read:

Intradermal air pouch leukocytosis as an in vivo test for nanoparticles

Vandooren J, Berghmans N, Dillen C, Van Aelst I, Ronsse I, Israel LL, Rosenberger I, Kreuter J, Lellouche JP, Michaeli S, Locatelli E, Comes Franchini M, Aiertza MK, Sánchez-Abella L, Loinaz I, Edwards DR, Shenkman L, Opdenakker G

International Journal of Nanomedicine 2013, 8:4745-4756

Published Date: 13 December 2013

A nonviral pHEMA+chitosan nanosphere-mediated high-efficiency gene delivery system

Eroglu E, Tiwari PM, Waffo AB, Miller ME, Vig K, Dennis VA, Singh SR

International Journal of Nanomedicine 2013, 8:1403-1415

Published Date: 11 April 2013

Modified supracricoid laryngectomy: oncological and functional outcomes in the elderly

Allegra E, Franco T, Trapasso S, Domanico R, La Boria A, Garozzo A

Clinical Interventions in Aging 2012, 7:475-480

Published Date: 8 November 2012

Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering

Hajiali H, Shahgasempour S, Naimi-Jamal MR, Peirovi H

International Journal of Nanomedicine 2011, 6:2133-2141

Published Date: 27 September 2011

Nab-paclitaxel for the treatment of breast cancer: efficacy, safety, and approval

Yamamoto Y, Kawano I, Iwase H

OncoTargets and Therapy 2011, 4:123-136

Published Date: 18 July 2011

Zinc oxide nanoparticles as selective killers of proliferating cells

Taccola L, Raffa V, Riggio C, Vittorio O, Iorio MC, Vanacore R, Pietrabissa A, Cuschieri A

International Journal of Nanomedicine 2011, 6:1129-1140

Published Date: 30 May 2011

Recent advances of chitosan nanoparticles as drug carriers

Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL

International Journal of Nanomedicine 2011, 6:765-774

Published Date: 11 April 2011

The use of nanocrystalline cellulose for the binding and controlled release of drugs

John K Jackson, Kevin Letchford, Benjamin Z Wasserman, et al

International Journal of Nanomedicine 2011, 6:321-330

Published Date: 10 February 2011

Case of endogenous endophthalmitis caused by Streptococcus equisimilis

Shinsuke Suemori, Akira Sawada, Shinya Komori, et al

Clinical Ophthalmology 2010, 4:917-918

Published Date: 12 August 2010