The Potential Protective Role of Caveolin-1 in Intestinal Inflammation in TNBS-Induced Murine Colitis |
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Authors: | Carolyn R. Weiss Qingdong Guan Yanbing Ma Gefei Qing Charles N. Bernstein Richard J. Warrington Zhikang Peng |
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Affiliation: | 1. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.; 2. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.; 3. Department of Pathology, University of Manitoba, Winnipeg, Manitoba, Canada.; 4. Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.; 5. IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada.; Charité, Campus Benjamin Franklin, GERMANY, |
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Abstract: | BackgroundCaveolin-1 (Cav-1) is a multifunctional scaffolding protein serving as a platform for the cell’s signal-transduction and playing an important role in inflammation. However, its role in inflammatory bowel disease is not clear. A recent study showed that Cav-1 is increased and mediates angiogenesis in dextran sodium sulphate-induced colitis, which are contradictory to our pilot findings in 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. In the present study, we further clarified the role of Cav-1 in TNBS-induced colitis.MethodsIn BALB/c mice, acute colitis was induced by intra-rectal administration of one dose TNBS, while chronic colitis was induced by administration of TNBS once a week for 7 weeks. To assess the effects of complete loss of Cav-1, Cav-1 knockout (Cav-1−/−) and control wild-type C57 mice received one TNBS administration. Body weight and clinical scores were monitored. Colon Cav-1 and pro-inflammatory cytokine levels were quantified through ELISAs. Inflammation was evaluated through histological analysis.ResultsColon Cav-1 levels were significantly decreased in TNBS-induced colitis mice when compared to normal mice and also inversely correlated with colon inflammation scores and proinflammatory cytokine levels (IL-17, IFN-γ and TNF) significantly. Furthermore, after administration of TNBS, Cav-1−/− mice showed significantly increased clinical and colon inflammatory scores and body weight loss when compared with control mice.Conclusions and SignificanceCav-1 may play a protective role in the development of TNBS-induced colitis. Our findings raise an important issue in the evaluation of specific molecules in animal models that different models may exhibit opposite results because of the different mechanisms involved. |
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