The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium
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
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
Published Date: 12 February 2013
Readers of this article also read:
Antitumor activity of docetaxel-loaded polymeric nanoparticles fabricated by Shirasu porous glass membrane-emulsification technique
Yu YN, Tan SW, Zhao S, Zhuang XT, Song QL, Wang YL, Zhou Q, Zhang ZP
Published Date: 29 July 2013
Published Date: 6 May 2013
Public banking of umbilical cord blood or storage in a private bank: testing social and ethical policy in northeastern Italy
Parco S, Vascotto F, Visconti P
Published Date: 10 April 2013
The combination of corneal collagen crosslinking with riboflavin and ultraviolet-a irridation and excimer laser surgery.
Ralla B, Holtmann C, Geerling G
Published Date: 26 March 2013
Optical coherence tomography and fundus autofluorescence imaging study of chorioretinal atrophy involving the macula in Alagille syndrome
Makino S, Ohkubo Y, Tampo H
Published Date: 6 September 2012
Umland EM, Falconieri L
Published Date: 5 July 2012
Monden Y, Sugita M, Yamakawa R, Nishimura K
Published Date: 22 June 2012
Nonselective ß-blocker propranolol for orbital and periorbital hemangiomas in infants: a new first-line of treatment?
El-Essawy R, Galal R, Abdelbaki S
Published Date: 18 November 2011
Seven-year retrospective analysis of the myopic control effect of orthokeratology in children: a pilot study
Alan Kwok-Hei Mok, Cindy Sin-Ting Chung
Published Date: 1 February 2011
Ticagrelor: An investigational oral antiplatelet treatment for reduction of major adverse cardiac events in patients with acute coronary syndrome
Eitan Abergel, Eugenia Nikolsky
Published Date: 19 October 2010