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Differential Susceptibility of Multidrug Resistance Protein-1 Deficient Mice to DSS and TNBS-Induced Colitis

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Abstract

The molecular mechanisms underlying inflammatory bowel diseases (IBD) are incompletely characterized. MRP-1, normally expressed in the large and small bowel epithelium, serves as a multidrug resistance protein. In this report we explored the role of MRP1 in IBD. Mrp1-deficient mice (mrp1 −/−) were subjected to two different models of IBD. The mrp1 −/− mice and wild-type (WT) mice showed equal induction of TNBS colitis, a hapten-induced T-cell mediated disease. However, in DSS colitis more severe disease was observed in mrp1 −/− mice. In a survival study, mortality of mrp1 −/− mice was higher. In nonlethal DSS colitis, the mean histological colitis score was significantly higher in mrp1 −/− mice and showed particularly severe epithelial damage. Although endogenous LTB4 levels were significantly increased in mrp1 −/− mice, treatment with a LTB4 antagonist did not reduce disease. We conclude that MRP-1 has an important role in the intestinal epithelial resistance to exogenous injury, but MRP-1 does not affect T-lymphocyte mediated mucosal damage.

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Authors and Affiliations

  1. Department of Experimental Internal Medicine, The Netherlands Institute of Ophthalmic Research Organisation, Amsterdam, The Netherlands

    Tessa Ten Hove, Anje A. te Velde & Sander J.H. van Deventer

  2. Department of Pathology, Academic Medical Centre, The Netherlands Institute of Ophthalmic Reseaerch Organisation, Amsterdam, The Netherlands

    Paul Drillenburg

  3. Department of Ophthalmogenetics, The Netherlands Institute of Ophthalmic Research Organisation, Amsterdam, The Netherlands

    Jan Wijnholds

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  1. Tessa Ten Hove
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  2. Paul Drillenburg
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  4. Anje A. te Velde
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  5. Sander J.H. van Deventer
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Ten Hove, T., Drillenburg, P., Wijnholds, J. et al. Differential Susceptibility of Multidrug Resistance Protein-1 Deficient Mice to DSS and TNBS-Induced Colitis. Dig Dis Sci 47, 2056–2063 (2002). https://doi.org/10.1023/A:1019629013945

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