Dataset Information

Effect of interleukin-1? on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease.

ABSTRACT: BACKGROUND:Mucosal imbalance of interleukin (IL)-1? and IL-1 receptor antagonist (Ra) has been reported in the duodenal mucosa of dogs with inflammatory bowel disease (IBD). However, the imbalance in the colonic mucosa and its role in duodenitis and colitis in IBD of dogs remain unclear. OBJECTIVES:To measure the expression of IL-1? and IL-1Ra proteins in the colonic mucosa of dogs with IBD, and to determine the effect of IL-1? on expression of occludin (ocln) mRNA, a tight junction component, in the duodenal and colonic mucosa of dogs with IBD. ANIMALS:Twelve dogs with IBD and 6 healthy dogs. METHODS:IL-1? and IL-1 Ra proteins in the colonic mucosa were quantified by ELISA in 7 of the 12 dogs with IBD. Expression of ocln mRNA in the duodenal and colonic mucosa was examined in the 12 dogs by real-time PCR. RESULTS:The ratio of IL-1? to IL-1Ra in the colonic mucosa was significantly higher in dogs with IBD than in healthy dogs. The ex vivo experiment determined that IL-1? suppressed expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, of healthy dogs. Expression of ocln mRNA in the colonic mucosa, but not in the duodenal mucosa, was significantly lower in dogs with IBD than in healthy dogs. CONCLUSIONS AND CLINICAL IMPORTANCE:A relative increase in IL-1? may attenuate ocln expression, leading to intestinal barrier dysfunction and promotion of intestinal inflammation in the colonic mucosa, but not in the duodenal mucosa, of dogs with IBD.

SUBMITTER: Ogawa M

PROVIDER: S-EPMC5980446 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Effect of interleukin-1β on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease.

Ogawa Misato M Osada Hironari H Hasegawa Ayana A Ohno Hikaru H Yanuma Nanako N Sasaki Kazuaki K Shimoda Minoru M Shirai Junsuke J Kondo Hirotaka H Ohmori Keitaro K

Journal of veterinary internal medicine 20180323 3

<h4>Background</h4>Mucosal imbalance of interleukin (IL)-1β and IL-1 receptor antagonist (Ra) has been reported in the duodenal mucosa of dogs with inflammatory bowel disease (IBD). However, the imbalance in the colonic mucosa and its role in duodenitis and colitis in IBD of dogs remain unclear.<h4>Objectives</h4>To measure the expression of IL-1β and IL-1Ra proteins in the colonic mucosa of dogs with IBD, and to determine the effect of IL-1β on expression of occludin (ocln) mRNA, a tight juncti ...[more]

PMID: 29572935

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Project description:BackgroundPeroxisome proliferator-activated receptors are nuclear receptors highly expressed in intestinal epithelial cells (IEC) and immune cells within the gut mucosa and are implicated in modulating inflammation and immune responses. The objective of this study was to investigate the effect of targeted deletion of PPAR gamma in IEC on progression of experimental inflammatory bowel disease (IBD).Methodology/principal findingsIn the first phase, PPAR gamma flfl; Villin Cre- (VC-) and PPAR gamma flfl; Villin Cre+ (VC+) mice in a mixed FVB/C57BL/6 background were challenged with 2.5% dextran sodium sulfate (DSS) in drinking water for 0, 2, or 7 days. VC+ mice express a transgenic recombinase under the control of the Villin-Cre promoter that causes an IEC-specific deletion of PPAR gamma. In the second phase, we generated VC- and VC+ mice in a C57BL/6 background that were challenged with 2.5% DSS. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to phenotypically characterize lymphocyte and macrophage populations in blood, spleen and mesenteric lymph nodes. Global gene expression analysis was profiled using Affymetrix microarrays. The IEC-specific deficiency of PPAR gamma in mice with a mixed background worsened colonic inflammatory lesions, but had no effect on disease activity (DAI) or weight loss. In contrast, the IEC-specific PPAR gamma null mice in C57BL/6 background exhibited more severe inflammatory lesions, DAI and weight loss in comparison to their littermates expressing PPAR gamma in IEC. Global gene expression profiling revealed significantly down-regulated expression of lysosomal pathway genes and flow cytometry results demonstrated suppressed production of IL-10 by CD4+ T cells in mesenteric lymph nodes (MLN) of IEC-specific PPAR gamma null mice.Conclusions/significanceOur results demonstrate that adequate expression of PPAR gamma in IEC is required for the regulation of mucosal immune responses and prevention of experimental IBD, possibly by modulation of lysosomal and antigen presentation pathways.

Project description:BackgroundUlcerative Colitis (UC) and Crohn's Disease (CD) are two chronic Inflammatory Bowel Diseases (IBD) affecting the intestinal mucosa. Current understanding of IBD pathogenesis points out the interplay of genetic events and environmental cues in the dysregulated immune response. We hypothesized that dysregulated microRNA (miRNA) expression may contribute to IBD pathogenesis. miRNAs are small, non-coding RNAs which prevent protein synthesis through translational suppression or mRNAs degradation, and regulate several physiological processes.Methodology/findingsExpression of mature miRNAs was studied by Q-PCR in inactive colonic mucosa of patients with UC (8), CD (8) and expressed relative to that observed in healthy controls (10). Only miRNAs with highly altered expression (>5 or <0.2 -fold relative to control) were considered when Q-PCR data were analyzed. Two subsets of 14 (UC) and 23 (CD) miRNAs with highly altered expression (5.2->100 -fold and 0.05-0.19 -fold for over- and under- expression, respectively; 0.001<p?0.05) were identified in quiescent colonic mucosa, 8 being commonly dysregulated in non-inflamed UC and CD (mir-26a,-29a,-29b,-30c,-126*,-127-3p,-196a,-324-3p). Several miRNA genes with dysregulated expression co-localize with acknowledged IBD-susceptibility loci while others, (eg. clustered on 14q32.31), map on chromosomal regions not previously recognized as IBD-susceptibility loci. In addition, in silico clustering analysis identified 5 miRNAs (mir-26a,-29b,-126*,-127-3p,-324-3p) that share coordinated dysregulation of expression both in quiescent and in inflamed colonic mucosa of IBD patients. Six miRNAs displayed significantly distinct alteration of expression in non-inflamed colonic biopsies of UC and CD patients (mir-196b,-199a-3p,-199b-5p,-320a,-150,-223).Conclusions/significanceOur study supports miRNAs as crucial players in the onset and/or relapse of inflammation from quiescent mucosal tissues in IBD patients. It allows speculating a role for miRNAs as contributors to IBD susceptibility and suggests that some of the miRNA with altered expression in the quiescent mucosa of IBD patients may define miRNA signatures for UC and CD and help develop new diagnostic biomarkers.

Dataset Information

Effect of interleukin-1? on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease.

Publications

Effect of interleukin-1β on occludin mRNA expression in the duodenal and colonic mucosa of dogs with inflammatory bowel disease.

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