Differential susceptibility of multidrug resistance protein-1 deficient mice to DSS and TNBS-induced colitis.
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.
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000172:deficiency* / Q000502:physiology; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D016264:Dextran Sulfate; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007975:Leukotriene B4; D017997:Leukotriene C4; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate