Activation of nuclear factor-kappaB in dogs with chronic enteropathies.

TitleActivation of nuclear factor-kappaB in dogs with chronic enteropathies.
Publication TypeJournal Article
Year of Publication2010
AuthorsLuckschander N, Hall JA, Gaschen F, Forster U, Wenzlow N, Hermann P, Allenspach K, Dobbelaere D, Burgener IA, Welle M
JournalVeterinary immunology and immunopathology
Volume133
Issue2-4
Pagination228-36
Date Published2010 Feb 15
ISSN1873-2534
KeywordsAnimals, Antibodies, Monoclonal, Case-Control Studies, Chronic Disease, Dog Diseases, Dogs, Immunohistochemistry, Inflammatory Bowel Diseases, Intestinal Diseases, Intestinal Mucosa, Macrophages, Mice, NF-kappa B
Abstract

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-kappaB (NF-kappaB) binding sites, which allow NF-kappaB to regulate gene transcription. The purpose of this study was to investigate (1) the occurrence of NF-kappaB activation during mucosal inflammation in situ, (2) the mucosal distribution pattern of cells expressing activated NF-kappaB within treatment groups, and (3) the effect of specific therapy on NF-kappaB 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-kappaB activation was detected in duodenal mucosal biopsies using a mouse monoclonal antibody (MAB 3026) that selectively binds the nuclear localization sequence of activated NF-kappaB. To identify macrophages, biopsies were stained using the MAC 387 antibody. Macrophages in the lamina propria double-stained for MAC 387 and NF-kappaB were quantitated; epithelial cell expression of activated NF-kappaB was determined semi-quantitatively. Results showed that more macrophages positive for activated NF-kappaB were present in lamina propria of dogs with chronic enteropathy compared to control dogs (p<0.01). More NF-kappaB positive epithelial 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-kappaB decreased (p<0.01) in chronic enteropathy dogs. In conclusion, activation of NF-kappaB is closely associated with the pathophysiology of canine chronic enteropathy. Down-regulation follows successful therapy.

Alternate JournalVet. Immunol. Immunopathol.