Expression of epithelial cell-derived cytokine genes in the duodenal and colonic mucosae of dogs with chronic enteropathy

Self Cite

BackgroundMucosal 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.ObjectivesTo 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 junction component, in the duodenal and colonic mucosa of dogs with IBD.AnimalsTwelve dogs with IBD and 6 healthy dogs.MethodsIL‐1β 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.ResultsThe ratio of IL‐1β 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‐1β 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 ImportanceA relative increase in IL‐1β 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.

Section: Methodsmentioning

confidence: 99%

Section: Dogsmentioning

confidence: 99%

See 1 more Smart Citation

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

Ogawa

Osada

Hasegawa

et al. 2018

Self Cite

“…Several reports describe various components of the cytokine signature (interleukin [IL]‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p40, IL‐17, IL‐18, IL‐23, IL‐25, IL‐33, IFN‐γ, TNF‐α, and TGF‐β1) in dogs with CIE,137, 138, 139, 140, 141, 142, 143 all of which do not support a Th1 nor Th2 polarization as described for inflammatory bowel diseases in humans 144, 145. There also is no evidence of a Th17 signature in dogs with CIE 146, 147.…”

Section: Biomarkers In Chronic Inflammatory Enteropathies Of Dogsmentioning

confidence: 99%

Clinical utility of currently available biomarkers in inflammatory enteropathies of dogs

Heilmann

Steiner

2018

Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food‐responsive, antibiotic‐responsive, or immunosuppressant‐responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein‐losing enteropathy. Disease‐independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1‐proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C‐reactive protein, perinuclear anti‐neutrophilic cytoplasmic antibodies, 3‐bromotyrosine, N‐methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

“…This finding is in contrast to a previous study, which documented significantly decreased mRNA expression of IL-33 in the duodenum of dogs with food-responsive enteropathy (FRE) compared to healthy Beagle dogs. 37 The lack of significance in our study might be because of the inclusion of different non-GSD breeds of dogs with CE, whereas the previous study contained 7 dogs, each a different non-GSD breed with FRE and only 1 of the dogs in our non-GSD group was the same breed. In addition, our study did not sub- Interleukin-13 is a Th2 cytokine that is produced mainly by T cells and natural killer cells.…”

Section: Discussionmentioning

confidence: 76%

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

Kathrani

Lezcano

Hall

et al. 2019

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.