Activation of nuclear factor-kappa B in dogs with chronic enteropathies

作者:Luckschander Nicole; Hall Jean A*; Gaschen Frederic; Forster Ursula; Wenzlow Nanny; Hermann Pascal; Allenspach Karin; Dobbelaere Dirk; Burgener Iwan A; Welle Monika
来源:Veterinary Immunology and Immunopathology, 2010, 133(2-4): 228-236.
DOI:10.1016/j.vetimm.2009.08.014

摘要

Homeostasis in the intestinal microenvironment between the immune system and luminal antigens appears disturbed in chronic enteropathies. Pro-inflammatory cytokines likely play a role in the pathogenesis of intestinal inflammation. Several inflammatory and immunoregulatory genes have associated nuclear factor-kappa B (NF-kappa B) binding sites, which allow NF-kappa B to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappa B activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappa B within treatment groups, and (3) the effect of specific therapy on NF-kappa B activation. Dogs with chronic enteropathy were studied (n = 26) and compared with 13 healthy dogs. Ten dogs had food responsive disease (FRD) and 16 had inflammatory bowel disease (IBD). NF-kappa B activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappa B. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappa B were quantitated; epithelial cell expression of activated NF-kappa B was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappa B were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p < 0.01). More NF-kappa B positive epithelia] cells were observed in FRD dogs compared to IBD dogs (p < 0.05). After therapy, the number of macrophages and epithelial cells staining positive for activated NF-kappa B decreased (p < 0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappa B is closely associated with the pathophysiology of canine chronic enteropathy. Downregulation follows successful therapy. Published by Elsevier B.V.

  • 出版日期2010-2-15