Artikel
Impact of the specific JNK inhibitor D-JNK-1on acute and chronic colitis in a DSS mouse model
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Veröffentlicht: | 20. Mai 2011 |
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Gliederung
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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.