Correlation between toll-like receptor 4 and nucleotide-binding oligomerization domain 2 (NOD2) and pathological severity in dogs with chronic gastrointestinal diseases

• Published in: Veterinary immunology and immunopathology 2019-04, Vol.210, p.15-22
• Main Authors: Aono, Kimiya, Azuma, Yasu-Taka, Nabetani, Tomoyo, Hatoya, Shingo, Furuya, Masaru, Miki, Mariko, Hirota, Kana, Fujimoto, Yasuyuki, Nishiyama, Kazuhiro, Ogata, Yoshiyuki, Mochizuki, Tomofumi, Tani, Hiroyuki
• Format: Article
• Language: English
• Subjects: Animals; Biopsy; Chronic Disease; Chronic gastrointestinal diseases; Colon - immunology; Colon - pathology; Dog; Dogs; Duodenum - immunology; Duodenum - pathology; Female; Gastrointestinal Diseases - immunology; Gastrointestinal Diseases - pathology; Male; NOD2; Nod2 Signaling Adaptor Protein - genetics; Severity of Illness Index; Signal Transduction; Stomach - immunology; Stomach - pathology; TLR4; Toll-Like Receptor 4 - genetics; Tumor Necrosis Factor-alpha - genetics
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2019.03.003

•TLR4 in the ileum of dogs with chronic gastrointestinal disease was positively associated with the severity.•NOD2 in duodenum, stomach, and rectum of dogs with chronic gastrointestinal disease was positively associated with severity.•There is no correlation between TNF-α in dogs with chronic gastrointestinal disease and the severity. Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain 2 (NOD2), and TNF-α play important roles in human inflammatory bowel diseases. The aim of this study was to elucidate the relationship between Toll-like receptor 4, NOD2, and TNF-α and the severity of chronic gastrointestinal diseases in dogs. We examined the expression levels of TLR4, NOD2, and TNF-α in the stomach, duodenum, ileum, colon, and rectum obtained from 21 dogs with chronic gastrointestinal disease, including inflammatory bowel disease, high-grade lymphoma, food responsive enteropathy, chronic pancreatitis, low-grade lymphoma, inflammatory colorectal polyp, and chronic colitis. Next, we demonstrated whether there is good correlation between the expression levels of TLR4, NOD2, and TNF-α and the histopathological analysis of each sample. We found that the level of TLR4 expression in the ileum of dogs with chronic gastrointestinal disease was positively associated with the histopathological severity. We also found that the level of NOD2 expression in the duodenum, stomach, and rectum was positively associated with the histopathological severity. However, there was no correlation between TNF-α expression in the 5 regions tested in this study and the histopathological severity. These findings indicate that TLR4 and NOD2 are remarkably associated with the severity of chronic gastrointestinal disease in dogs.