Differential susceptibility of multidrug resistance protein-1 deficient mice to DSS and TNBS-induced colitis

• Published in: Digestive diseases and sciences Vol. 47; no. 9; pp. 2056 - 2063
• Main Authors: TEN HOVE, Tessa, DRILLENBURG, Paul, WIJNHOLDS, Jan, TE VELDE, Anje A, VAN DEVENTER, Sander J. H
• Format: Journal Article
• Language: English
• Published: Heidelberg Springer 01.09.2002; Springer Nature B.V
• Subjects: Animals; ATP Binding Cassette Transporter, Subfamily B, Member 1 - deficiency; ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology; Biological and medical sciences; Colitis - chemically induced; Colitis - immunology; Colitis - metabolism; Colon - metabolism; Dextran Sulfate; Digestive system; Investigative techniques, diagnostic techniques (general aspects); Leukotriene B4 - metabolism; Leukotriene C4 - metabolism; Medical sciences; Mice; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; T-Lymphocytes - immunology; Trinitrobenzenesulfonic Acid; Drug; Multiple; Induction; Deficiency; Rodentia; Cell differentiation; Epithelium; Protein; Inflammatory disease; Resistance; Pathology; Crohn disease; Vertebrata; Sensitivity; Mammalia; Histopathology; Mouse; Animal; Digestive diseases; Intestinal disease; Colitis; Biological effect; Ulcerative colitis
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1023/a:1019629013945

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.