Dataset Information

Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.

ABSTRACT:

Background

Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD.

Methodology/principal findings

Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1?, IL-1?, TLR2, TLR4, PRNP were all significantly up-regulated, while PPAR? was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1?. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing.

Conclusions/significance

Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene expression analyses. TNBS-colitis is an appropriate model to study specific biological processes in IBD.

SUBMITTER: Brenna O

PROVIDER: S-EPMC3561356 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.

Brenna Øystein Ø Furnes Marianne W MW Drozdov Ignat I van Beelen Granlund Atle A Flatberg Arnar A Sandvik Arne K AK Zwiggelaar Rosalie T M RT Mårvik Ronald R Nordrum Ivar S IS Kidd Mark M Gustafsson Björn I BI

PloS one 20130131 1

<h4>Background</h4>Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is ...[more]

PMID: 23382912

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Project description:BackgroundIncreasing evidence is suggesting appendectomy as an alternative treatment for ulcerative colitis (UC), especially in case of histological appendiceal inflammation. Therefore, preoperative identification of appendiceal inflammation could be beneficial. This study aimed to assess the prevalence of peri-appendiceal red patch (PARP) on colonoscopy. In addition, prognostic relevance of PARP for disease course and its predictive value for histological appendiceal inflammation in patients undergoing appendectomy was assessed.MethodsUC patients undergoing colonoscopy in 2014/2015 were included to determine PARP-prevalence in a cross-sectional study. Findings were correlated to patient and disease characteristics, upscaling of treatment and colectomy rates after cross-sectional colonoscopy. In patients undergoing appendiceal resection, histopathological inflammation was assessed using the Robarts Histopathology Index (RHI).ResultsIn total, 249 patients were included of which 17.7% (44/249) had a PARP. Patients with PARP were significantly younger with a shorter disease course. The majority of patients with PARP (61.4%) was in endoscopic remission. Patients with PARP required more upscaling of medical therapy (81.8% vs. 58.0%, p < 0.01), and more PARP patients underwent colectomy (13.6% vs. 4.9%, p = 0.04). Patients with PARP had a higher median RHI in resection specimens (14 vs. 7, p < 0.01).ConclusionPARP was present during colonoscopy regardless disease activity and was predominantly found in UC patients with younger age and shorter disease duration. PARP patients had a more severe course of UC, and in case of appendectomy, more severe histopathological appendiceal inflammation. Appendectomy as an experimental therapy for UC has been suggested to be predominantly effective in UC patients with appendiceal inflammation. This study demonstrates that presence of a PARP on colonoscopy predicts appendiceal inflammation. After consensus has been reached on the therapeutic effect of appendectomy, assessing PARP presence during colonoscopy could therefore contribute to identifying patients most likely to respond.

Dataset Information

Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.

Background

Methodology/principal findings

Conclusions/significance

Publications

Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.

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