Reduction of MDR1, MRP1 and BCRP expression in Crohn’s disease: a role in disease pathogenesis?

Abstract

Abstract

Background and purpose: ABC transporters have non-redundant role in the maintenance of gut homeostasis and altered expression may contribute to the Crohn’s disease pathology. As they are closely regulated by the inflammatory milieu, the coexpression of ABC transporters, relevant proinflammatory cytokines and their negative regulators in affected tissues could provide insight to pathological pattern of Crohn’s disease related to different disease phases.

Materials and Methods: Crohn’s disease patients were divided into three subgroups: newly diagnosed (untreated), active disease on therapy (treated) and remission. Intestine mucosa from terminal ileum to rectum was compared to mucosa from healthy controls for mRNA expression of MDR1, MRP1 and BCRP1. Affected terminal ileum and unaffected sigmoid colon mucosa were compared to controls for mRNA expression of cytokines and suppressor of cytokine signalling molecules.

Results: MDR1 mRNA expression is downregulated at inflamed tissues irrespective of patient subgroups. MRP1 expression is reduced in untreated group and normalized after therapy introduction. Inflamed ileum was characterised by transitory increase in IFN-γ, IL-17A and SOCS3 mRNA expression levels in treated group. In the unaffected colon, no significant difference in the expression of the tested transporters was observed, even though IFN-γ, IL-2 and IL-1b expression was increased.

Conclusion: Reduced MDR1 expression, irrespective of the disease group, and reduced MRP1 expression in untreated group, implicates the involvement of these transporters in the disease pathogenesis. The affected ileum lacks increased cytokine expression, while unaffected colon mucosa shows a Th1 cytokine profile.