Activation of nuclear factor-kappaB in dogs with chronic enteropathies.
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.
Luckschander
Nicole
N
Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Hall
Jean A
JA
Gaschen
Frédéric
F
Forster
Ursula
U
Wenzlow
Nanny
N
Hermann
Pascal
P
Allenspach
Karin
K
Dobbelaere
Dirk
D
Burgener
Iwan A
IA
Welle
Monika
M
D000818:Animals; D000911:Antibodies, Monoclonal; D016022:Case-Control Studies; D002908:Chronic Disease; D004283:Dog Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004285:Dogs; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D007410:Intestinal Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D016328:NF-kappa B