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

J Vet Intern Med. 2018 May;32(3):1019-1025. doi: 10.1111/jvim.15117. Epub 2018 Mar 23.

Abstract

Background: Mucosal 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.

Objectives: To 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.

Animals: Twelve dogs with IBD and 6 healthy dogs.

Methods: IL-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.

Results: The 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 importance: A 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.

Keywords: chronic enteropathy; inflammatory cytokine; intestinal barrier dysfunction; tight junction.

MeSH terms

  • Animals
  • Case-Control Studies
  • Colon / metabolism*
  • Dog Diseases / metabolism*
  • Dogs
  • Duodenum / metabolism*
  • Female
  • Gene Expression
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / veterinary*
  • Interleukin-1beta / metabolism*
  • Intestinal Mucosa / metabolism*
  • Male
  • Occludin / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-1 / metabolism
  • Tight Junctions / metabolism

Substances

  • Interleukin-1beta
  • Occludin
  • RNA, Messenger
  • Receptors, Interleukin-1