ArticlePloS one2012
TLR5 risk-associated haplotype for canine inflammatory bowel disease confers hyper-responsiveness to flagellin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 59 citations in OpenAlex.
- Are single nucleotide polymorphisms underutilized for guiding treatment of inflammatory bowel disease?Immunology and cell biology · 2025Review
- Effects ofVeterinary sciences · 2024Article
- Genomic Medicine in Canine Periodontal Disease: A Systematic Review.Animals : an open access journal from MDPI · 2023Review
- Elucidating the Role of Innate and Adaptive Immune Responses in the Pathogenesis of Canine Chronic Inflammatory Enteropathy-A Search for Potential Biomarkers.Animals : an open access journal from MDPI · 2022Review
- Brazilian Organic Honey from Atlantic Rainforest Decreases Inflammatory Process in Mice.Veterinary sciences · 2022Article
- Activation of Canine, Mouse and Human TLR2 and TLR4 by InactivatedFrontiers in immunology · 2022Article
- Canine chronic enteropathy-Current state-of-the-art and emerging concepts.Frontiers in veterinary science · 2022Review
- Harnessing the Biology of Canine Intestinal Organoids to Heighten Understanding of Inflammatory Bowel Disease Pathogenesis and Accelerate Drug Discovery: A One Health Approach.Frontiers in toxicology · 2021Review
- Toward a porcineGut microbes · 2020Article
- Identification of Genetic Susceptibility Factors Associated with Canine Gastric Dilatation-Volvulus.Genes · 2020Article
- Functional expression of TLR5 of different vertebrate species and diversification in intestinal pathogen recognition.Scientific reports · 2018Article
- Article
- Intestinal Stem Cells to Advance Drug Development, Precision, and Regenerative Medicine: A Paradigm Shift in Translational Research.The AAPS journal · 2017Review
- A descriptive pilot study of cytokine production following stimulation of ex-vivo whole blood with commercial therapeutic feline hydrolyzed diets in individual healthy immunotolerant cats.BMC veterinary research · 2017Article
- miR-15a/16 reduces retinal leukostasis through decreased pro-inflammatory signaling.Journal of neuroinflammation · 2016Article
- Diagnosis of Small Intestinal Disorders in Dogs and Cats.Clinics in laboratory medicine · 2015Review
- Functional analysis of pattern recognition receptors in miniature dachshunds with inflammatory colorectal polyps.The Journal of veterinary medical science · 2015Article
- Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs.World journal of gastroenterology · 2014Review
- Non-synonymous genetic variation in exonic regions of canine Toll-like receptors.Canine genetics and epidemiology · 2014Article
- Diagnosis of small intestinal disorders in dogs and cats.The Veterinary clinics of North America. Small animal practice · 2013Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Single nucleotide polymorphisms (SNP) in the TLR5 gene have been associated with human inflammatory bowel disease (IBD) and animal models of this disease. We recently demonstrated a significant association between three non-synonymous SNPs in the canine TLR5 gene and IBD in German shepherd dogs (GSDs). However, so far, no direct link between these SNPs and a disturbance in TLR5 function was shown. In the present study, we determined the functional significance of the canine TLR5 SNPs by transfecting the identified risk-protective and risk-associated haplotype into human embryonic kidney cells (HEK) and assessed nuclear factor-kappa B (NF-κB) activation and CXCL8 production after stimulation. In addition, a whole blood assay for TLR5 activation was developed using blood derived from carrier dogs of either haplotype. There was a significant increase in NF-kB activity when cells transfected with the risk-associated TLR5 haplotype were stimulated with flagellin compared to the cells expressing the risk-protective TLR5 haplotype. This difference in NFkB activation correlated with CXCL8 expression in the supernatant measured by ELISA. Furthermore, whole blood taken from carrier dogs of the risk-associated TLR5 haplotype produced significantly more TNF after stimulation with flagellin compared to that taken from carriers of the risk-protective haplotype. Thus, we show for the first time a direct functional impact of the canine IBD risk-associated TLR5 haplotype, which results in hyper-responsiveness to flagellin compared to the IBD risk-protective TLR5 haplotype. Our data potentially suggest that similarly to human IBD and experimental models, TLR5 may also play a role in canine IBD. Blocking the hyper-responsive receptor found in susceptible dogs with IBD may alleviate the inappropriate inflammation seen in this disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.