Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) mRNA is over-expressed in the duodenal mucosa and is negatively correlated with serum tryptophan concentrations in dogs with protein-losing enteropathy.

INTRODUCTION: Dogs with protein-losing enteropathy (PLE) have decreased serum tryptophan concentrations, which may contribute to disease pathogenesis. Indoleamine-pyrrole 2,3-dioxygenase-1 (IDO-1) expression is associated with low serum tryptophan concentrations and is increased in the gastrointestinal tract of humans with inflammatory bowel disease (IBD). Therefore, the objective of our study was to determine if the mRNA expression of IDO-1 is increased in the duodenal mucosa of dogs with PLE as compared to dogs with chronic enteropathy (CE) and healthy dogs, and whether this expression is correlated with changes in serum tryptophan concentration. METHODS: Our study was a retrospective study using archived paraffin-embedded duodenal biopsy specimens from 8 healthy Beagle dogs from the Iowa State University Canine Service Colony and 18 and 6 client-owned dogs diagnosed with CE and PLE, respectively at the Bristol Veterinary School. A novel RNA in situ hybridization (ISH) technology, RNAscope, was used to identify IDO-1 mRNA mucosal expression in duodenal tissues. An IDO-1 specific probe was hybridized onto 10 duodenal biopsy sections from each dog whereby RNAscope signal (mRNA expression) was quantified by a single operator using light microscopy. RESULTS: Dogs with PLE had significantly higher mRNA expression of IDO-1 in the duodenal mucosa compared to healthy dogs (mucosal percentage IDO-1 positive: P = 0.0093, (mean ± S.D) control: 19.36 ± 7.08, PLE: 34.12 ± 5.98, average fold difference: 1.76 and mucosal IDO-1 H-score: P = 0.0356, (mean ± S.D) control: 45.26 ± 19.33, PLE: 84.37 ± 19.86, average fold difference: 1.86). The duodenal mucosal mRNA expression of IDO-1 was negatively correlated with serum tryptophan concentrations in dogs with PLE (mucosal IDO-1 H-score: Spearman's rank correlation coefficient = -0.94, P = 0.0048). CONCLUSIONS: In conclusion, our study suggests that decreased serum tryptophan concentrations in dogs with PLE is associated with increased intestinal IDO-1 expression. Further studies are needed to determine potential inflammatory pathways responsible for increased expression of IDO-1 in the intestinal tract of dogs with PLE.

Interleukin-13 and interleukin-33 mRNA are underexpressed in the duodenal mucosa of German Shepherd dogs with chronic enteropathy.

BACKGROUND: A recent genome-wide association study in German Shepherd dogs (GSDs) with chronic enteropathy (CE) has identified polymorphisms in the Th2 cytokine genes. HYPOTHESIS/OBJECTIVE: To determine if the expression of the Th2 cytokines, interleukin-13 (IL-13) and interleukin-33 (IL-33), is altered in the duodenal mucosa of GSDs with CE compared to non-GSDs with CE and healthy dogs. ANIMALS: Twenty client-owned dogs diagnosed with CE (10 GSDs and 10 non-GSDs) at the Bristol Veterinary School and 8 healthy Beagle dogs from the Iowa State University Service Colony. METHODS: Retrospective study using archived paraffin-embedded duodenal biopsy samples. A novel RNA in situ hybridization technology (RNAscope) was used to hybridize IL-13 and IL-33 mRNA probes onto at least 10 sections from duodenal biopsy samples for each dog. RNAscope signals were visualized using a microscope and semi-quantitative assessment was performed by a single operator. RESULTS: Based on duodenal villus, subvillus, epithelial, and lamina propria average expression scores, GSDs with CE had significantly lower IL-13 and IL-33 mRNA expression compared to non-GSDs with CE (IL-13, P < .04; IL-33, P < .02) and healthy Beagle dogs (IL-13, P < .02; IL-33, P < .004). CONCLUSIONS AND CLINICAL IMPORTANCE: Similar to human patients with ulcerative colitis, a subtype of human inflammatory bowel disease, these data indicate that Th2 cytokines may be involved in the pathogenesis of CE in GSDs.