Cyclooxygenase-2 and 5-lipoxygenase in dogs with chronic enteropathies

J Vet Intern Med. Nov-Dec 2014;28(6):1684-91. doi: 10.1111/jvim.12463. Epub 2014 Sep 30.

Abstract

Background: Cyclooxygenase-2 (COX-2) is a key enzyme in the synthesis of pro-inflammatory prostaglandins and 5-lipoxygenase (5-LO) is the major source of leukotrienes. Their role in IBD has been demonstrated in humans and animal models, but not in dogs with chronic enteropathies (CCE).

Hypothesis: COX-2 and 5-LO are upregulated in dogs with CCE.

Animals: Fifteen healthy control dogs (HCD), 10 dogs with inflammatory bowel disease (IBD), and 15 dogs with food-responsive diarrhea (FRD).

Methods: Prospective study. mRNA expression of COX-2, 5-LO, IL-1b, IL-4, IL-6, TNF, IL-10 and TFG-β was evaluated by quantitative real-time RT-PCR in duodenal and colonic biopsies before and after treatment.

Results: COX-2 expression in the colon was significantly higher in IBD and FRD before and after treatment (all P < .01). IL-1b was higher in FRD in the duodenum after treatment (P = .021). TGF-β expression was significantly higher in the duodenum of HCD compared to FRD/IBD before treatment (both P < .001) and IBD after treatment (P = .012). There were no significant differences among groups and within groups before and after treatment for IL-4, IL-6, TNF, and IL-10. There was a significant correlation between COX-2 and IL-1b in duodenum and colon before treatment in FRD and IBD, whereas 5-LO correlated better with IL-6 and TNF. IL-10 and TGF-β usually were correlated.

Conclusions and clinical importance: COX-2 is upregulated in IBD and FRD, whereas IL-1b and TGF-β seem to be important pro- and anti-inflammatory cytokines, respectively. The use of dual COX/5-LO inhibitors could be an interesting alternative in the treatment of CCE.

Keywords: Food-responsive diarrhea; Inflammatory bowel disease; Interleukin; Leukotriene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Arachidonate 5-Lipoxygenase / physiology
  • Case-Control Studies
  • Chronic Disease
  • Colon / chemistry
  • Colon / enzymology
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 / physiology
  • Diarrhea / enzymology
  • Diarrhea / veterinary*
  • Dog Diseases / enzymology*
  • Dogs
  • Duodenum / chemistry
  • Duodenum / enzymology
  • Female
  • Inflammatory Bowel Diseases / enzymology
  • Inflammatory Bowel Diseases / veterinary*
  • Interleukin-10 / analysis
  • Interleukin-1beta / analysis
  • Interleukin-4 / analysis
  • Male
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Transforming Growth Factor beta / analysis
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Interleukin-1beta
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2