engleski

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

Background and purpose: ABC transporters have a non-redundant role in the maintenance of gut homeostasis and changes in their 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 the affected tissues could provide an insight to the pathological pattern of Crohn’s disease related to different disease phases. Materials and Methods: Crohn’s disease patients were divided into three groups: newly diagnosed (untreated), active disease on therapy (treated) and remission. Intestinal mucosa from terminal ileum to rectum was compared to matching 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 relevant cytokines and suppressor of cytokine signaling molecules. Results: MDR1 mRNA expression is downregulated in inflamed tissues irrespective of patient groups. MRP1 expression is reduced in the untreated group and normalized after therapy introduction. Inflamed ileum was characterized by transitory increase in IFN-g, IL-17A and SOCS3 expression in the treated group. In the unaffected colon, no significant difference in the expression of the tested transporters was observed, even though IFN-g, 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.

Crohn’s disease; ABC transporters; MRP1 (ABCC1); MDR1 (ABCB1); BCRP (ABCG2); Cytokines; Suppressors of cytokine signaling molecules (SOCS)

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