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...
Guardado en:
| Autores principales: | , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/360a24a3528047c49be60a25d355c61b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:360a24a3528047c49be60a25d355c61b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:360a24a3528047c49be60a25d355c61b2021-12-02T02:38:24ZThe impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium1178-7031https://doaj.org/article/360a24a3528047c49be60a25d355c61b2013-05-01T00:00:00Zhttp://www.dovepress.com/the-impact-of-jnk-inhibitor-d-jnki-1-in-a-murine-model-of-chronic-coli-a12946https://doaj.org/toc/1178-7031Sabine 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-1Kersting SBehrendt VKersting JReinecke KHilgert CStricker IHerdegen TJanot MSUhl WChromik AMDove Medical PressarticlePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol 2013, Iss default, Pp 71-81 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Pathology RB1-214 Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Kersting S Behrendt V Kersting J Reinecke K Hilgert C Stricker I Herdegen T Janot MS Uhl W Chromik AM The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| description |
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 |
| format |
article |
| author |
Kersting S Behrendt V Kersting J Reinecke K Hilgert C Stricker I Herdegen T Janot MS Uhl W Chromik AM |
| author_facet |
Kersting S Behrendt V Kersting J Reinecke K Hilgert C Stricker I Herdegen T Janot MS Uhl W Chromik AM |
| author_sort |
Kersting S |
| title |
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| title_short |
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| title_full |
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| title_fullStr |
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| title_full_unstemmed |
The impact of JNK inhibitor D-JNKI-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| title_sort |
impact of jnk inhibitor d-jnki-1 in a murine model of chronic colitis induced by dextran sulfate sodium |
| publisher |
Dove Medical Press |
| publishDate |
2013 |
| url |
https://doaj.org/article/360a24a3528047c49be60a25d355c61b |
| work_keys_str_mv |
AT kerstings theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT behrendtv theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT kerstingj theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT reineckek theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT hilgertc theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT strickeri theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT herdegent theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT janotms theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT uhlw theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT chromikam theimpactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT kerstings impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT behrendtv impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT kerstingj impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT reineckek impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT hilgertc impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT strickeri impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT herdegent impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT janotms impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT uhlw impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium AT chromikam impactofjnkinhibitordjnki1inamurinemodelofchroniccolitisinducedbydextransulfatesodium |
| _version_ |
1718402277014765568 |