Digestive Diseases and Sciences

, Volume 47, Issue 9, pp 2056–2063

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

Authors

  • Tessa Ten Hove
    • Department of Experimental Internal Medicine, The Netherlands Institute of Ophthalmic Research Organisation
  • Paul Drillenburg
    • Department of Pathology, Academic Medical Centre, The Netherlands Institute of Ophthalmic Reseaerch Organisation
  • Jan Wijnholds
    • Department of Ophthalmogenetics, The Netherlands Institute of Ophthalmic Research Organisation
  • Anje A. te Velde
    • Department of Experimental Internal Medicine, The Netherlands Institute of Ophthalmic Research Organisation
  • Sander J.H. van Deventer
    • Department of Experimental Internal Medicine, The Netherlands Institute of Ophthalmic Research Organisation
Article

DOI: 10.1023/A:1019629013945

Cite this article as:
Ten Hove, T., Drillenburg, P., Wijnholds, J. et al. Dig Dis Sci (2002) 47: 2056. doi:10.1023/A:1019629013945

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.

inflammatory bowel diseasecolitismultidrug resistance proteinepithelium

Copyright information

© Plenum Publishing Corporation 2002