Bcl-2/caspase 3 mucosal imbalance favors T cell resistance to apoptosis in dogs with inflammatory bowel disease.
Canine idiopathic inflammatory bowel disease (IBD) is believed to result from complex interplay between genetic, microbial, and immunologic factors. Abnormal cell death by apoptosis may result in the persistence of activated intestinal T cells that contribute to mucosal inflammation and clinical severity. To test this hypothesis, we investigated the mucosal expression of pro- and anti-apoptotic proteins in different intestinal compartments and their association with inflammatory indices in dogs with IBD. Apoptosis of lamina propria (LP) T cells in duodenal, ileal, and colonic tissues in control and IBD dogs was analyzed by caspase 3/Bcl-2 immunohistochemistry and TUNEL assays. Densities and distributions of LP caspase 3 and Bcl-2 cells were correlated to histopathologic lesions and the clinical activity index (CIBDAI). Compared to control tissues, IBD dogs had significantly (P<0.01) fewer caspase 3 cells in colonic mucosa. Double immunostaining identified the majority of apoptotic cells as TUNEL(+)/caspase 3(+). Within intestinal mucosa of IBD dogs, there were significantly greater numbers of Bcl-2 cells at the apical and basilar villus in the duodenum as compared to the colon and to the apical and basilar villus in the ileum (P<0.001 for all comparisons). There were significantly greater numbers of Bcl-2 cells at the apical and basilar villus of the duodenum but significantly fewer numbers of Bcl-2 cells at the apical villus of the ileum in IBD dogs compared with controls (P<0.001, P<0.001, and P<0.02, respectively). There was a significant association between the number of Bcl-2 cells in the duodenum of IBD dogs and the CIBDAI (P<0.001 each for mild, moderate and severe clinical IBD). In conclusion, apoptosis of T lymphocytes varies within intestinal compartments of dogs with IBD. Mucosal imbalance of Bcl-2/caspase 3 expression favors T cell resistance to apoptosis which may contribute to T cell accumulation and chronic intestinal inflammation, similar to human IBD.
Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA 50010, USA. Electronic address: ajergens@iastate.edu.
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Jergens
Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA 50010, USA. Electronic address: youngjm@iastate.edu.
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Young
Department of Veterinary Pathology, Iowa State University, Ames, IA, USA. Electronic address: dgmoore@iastate.edu.
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Moore
Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, USA. Electronic address: chwang@mail.iastate.edu.
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Wang
Department of Veterinary Pathology, Iowa State University, Ames, IA, USA. Electronic address: jesseh@mail.iastate.edu.
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Hostetter
Department of Veterinary Clinical Sciences, Iowa State University, Ames, IA 50010, USA. Electronic address: laura.a.augustine@gmail.com.
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Augustine
Department of Veterinary Clinical Sciences, University of London, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK. Electronic address: kallenspach@rvc.ac.uk.
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Allenspach
Department of Veterinary Clinical Sciences, University of London, North Mymms, Hatfield AL9 7TA, Hertfordshire, UK. Electronic address: sschmitz@rvc.ac.uk.
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Schmitz
Department of Genetics, Development & Cell Biology, Iowa State University, Ames IA, USA. Electronic address: cmosher@iastate.edu.
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Mosher
D000818:Animals; D017209:Apoptosis; D016022:Case-Control Studies; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism*; D004283:Dog Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3
Apoptosis; Bcl-2; Caspase; Dog; Inflammatory bowel disease; T lymphocytes