期刊
JOURNAL OF CROHNS & COLITIS
卷 8, 期 2, 页码 147-160出版社
OXFORD UNIV PRESS
DOI: 10.1016/j.crohns.2013.08.002
关键词
Inflammatory bowel disease; Crohn's disease; Interleukin-10 knock out mouse; Piroxicam
资金
- Novo Nordisk - LIFE In Vivo Pharmacology Centre (LIFEPHARM)
- Department of Immunopharmacology, Novo Nordisk A/S
Background: In inflammatory bowel disease a defective mucosal barrier, a dysregulated immune response and an excessive reactivity against the gut microbiota are assumed to cause a breakdown of the intestinal homeostasis and lead to chronic inflammation. Piroxicam treatment is a method for induction of colitis in IL-10 k.o. mice, which integrates a dysfunction of both the intestinal barrier and the immune system. However, the translational value of this model has not been thoroughly clarified. Aim: To characterise the piroxicam-accelerated colitis (PAC) IL-10 k.o. model with respect to clinical features, pathogenic mechanisms and its ability to respond to existing therapies. Methods: The PAC IL-10 k.o. model was established on a C57BL/6 J background and the clinical manifestations, immunological mechanisms and efficacy of ampicillin and anti-IL-12/23p40 treatment were assessed. Results: The PAC IL-10 k.o. mice developed weight loss and diarrhoea, and colonoscopy revealed a thickened granulomatous mucosa. Histological evaluation of ileum and colon showed Crohn's disease-like changes with pronounced hyperplasia and focal transmural inflammation. Ileitis was also observed in piroxicam treated wild type mice. The total number of neutrophils, monocytes and natural killer cells was elevated in the blood compared to IL-10 k.o. and wild type mice, indicating a role of the innate immune system in the pathogenesis. These findings were supported by analyses of the intestinal cytokine profile. Ampicillin and anti-IL-12/23p40 treatment significantly suppressed disease in the model. Conclusion: The PAC IL-10 k.o. model resembles several features of Crohn's disease and could be a useful in vivo model in preclinical research. (C) 2013 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据