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Activation of nuclear factor-kappaB in dogs with chronic enteropathies.
|Title||Activation of nuclear factor-kappaB in dogs with chronic enteropathies.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Luckschander N, Hall JA, Gaschen F, Forster U, Wenzlow N, Hermann P, Allenspach K, Dobbelaere D, Burgener IA, Welle M|
|Journal||Veterinary immunology and immunopathology|
|Date Published||2010 Feb 15|
|Keywords||Animals, Antibodies, Monoclonal, Case-Control Studies, Chronic Disease, Dog Diseases, Dogs, Immunohistochemistry, Inflammatory Bowel Diseases, Intestinal Diseases, Intestinal Mucosa, Macrophages, Mice, NF-kappa B|
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 Journal||Vet. Immunol. Immunopathol.|