Reinecke, Kirstin, Eminel, Sevgi, Dierck, Franziska, Roessner, Wibke, Kersting, Sabine, Chromik, Ansgar Michael, Gavrilova, Olga, Laukevicience, Ale, Leuschner, Ivo, Waetzig, Vicki, Rosenstiel, Philip, Herdegen, Thomas and Sina, Christian (2012) The JNK Inhibitor XG-102 Protects against TNBS-Induced Colitis. PLoS ONE, 7 (3). DOI 10.1371/journal.pone.0030985.

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Abstract

The c-Jun N-terminal kinase (JNK)-inhibiting peptide D-JNKI-1, syn. XG-102 was tested for its therapeutic potential in acute inflammatory bowel disease (IBD) in mice. Rectal instillation of the chemical irritant trinitrobenzene sulfonic acid (TNBS) provoked a dramatic acute inflammation in the colon of 7-9 weeks old mice. Coincident subcutaneous application of 100 mu g/kg XG-102 significantly reduced the loss of body weight, rectal bleeding and diarrhoea. After 72 h, the end of the study, the colon was removed and immuno-histochemically analysed. XG-102 significantly reduced (i) pathological changes such as ulceration or crypt deformation, (ii) immune cell pathology such as infiltration and presence of CD3- and CD68-positive cells, (iii) the production of tumor necrosis factor (TNF)-alpha in colon tissue cultures from TNBS-treated mice, (iv) expression of Bim, Bax, FasL, p53, and activation of caspase 3, (v) complexation of JNK2 and Bim, and (vi) expression and activation of the JNK substrate and transcription factor c-Jun. A single application of subcutaneous XG-102 was at least as effective or even better depending on the outcome parameter as the daily oral application of sulfasalazine used for treatment of IBD. The successful and substantial reduction of the severe, TNBS-evoked intestinal damages and clinical symptoms render the JNK-inhibiting peptide XG-102 a powerful therapeutic principle of IBD.

Document Type:	Article
Research affiliation:	Kiel University OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	No
Publisher:	Public Library of Science
Projects:	Future Ocean
Date Deposited:	14 May 2014 09:40
Last Modified:	23 Sep 2019 23:38
URI:	https://oceanrep.geomar.de/id/eprint/24222

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