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

  • Tessa Ten Hove
  • Paul Drillenburg
  • Jan Wijnholds
  • Anje A. te Velde
  • Sander J.H. van Deventer
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

Authors and Affiliations

  • Tessa Ten Hove
    • 1
  • Paul Drillenburg
    • 2
  • Jan Wijnholds
    • 3
  • Anje A. te Velde
    • 1
  • Sander J.H. van Deventer
    • 1
  1. 1.Department of Experimental Internal Medicine, The Netherlands Institute of Ophthalmic Research OrganisationAmsterdamThe Netherlands
  2. 2.Department of Pathology, Academic Medical Centre, The Netherlands Institute of Ophthalmic Reseaerch OrganisationAmsterdamThe Netherlands
  3. 3.Department of Ophthalmogenetics, The Netherlands Institute of Ophthalmic Research OrganisationAmsterdamThe Netherlands