00803-A: Toll-Like Receptors in Dogs And Their Role in Intestinal Inflammation

Grant Status: Closed

Grant Amount: $12,897
Dr. Iwan Burgener, DVM, University of Bern
May 1, 2006 - April 30, 2007
Breed(s): -All Dogs
Research Program Area: Treatment

Abstract

Inflammatory bowel disease (IBD) is a common cause of chronic vomiting and diarrhea in dogs, but its true incidence is not known. The underlying etiology is unknown, and comparisons have been made with similar human conditions. Although IBD can potentially occur in any dog breed, certain predispositions are recognized, such as lymphocytic-plasmacytic enteritis in German Shepherds, lymphoproliferative enteropathy in Basenjis, and protein-losing enteropathy/nephropathy in Soft Coated Wheaten Terriers. Chinese Shar-Pei often have a severe lymphocytic-plasmacytic enteritis with hypoproteinemia and extremely low serum cobalamin concentrations. Toll-like receptors (TLRs) recognize certain pathogen-associated molecular patterns (PAMPs) present on bacteria, fungi, viruses and parasites. Signalling through these receptors results in activation of NF-?B, thereby leading to the production of proinflammatory cytokines, reactive oxygen and nitrogen intermediates, and an up-regulation of co-stimulatory molecules on the cell surface. Dysregulated expression of TLRs and abnormal activation of intestinal epithelial cells (IEC) and/or cells of the innate immune system by PAMPs has been implicated in the pathogenesis of human IBD. Canine IBD is characterized by inflammation of the gut mucosa in the absence of a known pathogen. The key goal of this part of the project is the identification and quantification of TLRs activated by PAMPs of bacterial origin. Canine TLR2, 4, and 9 mRNA will be measured throughout different parts of the healthy intestine and compared to endoscopic biopsies from dogs suffering of IBD and food-responsive diarrhea (FRD). We want to test the hypothesis that dysregulation of the immune response mediated by these TLRs is a key factor in the pathogenesis of canine IBD.

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