Efflux transporters in ulcerative colitis: Decreased expression of BCRP (ABCG2) and Pgp (ABCB1)
Gunilla Englund PhD
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorAnnica Jacobson PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorFredrik Rorsman MD, PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorPer Artursson PhD
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorAndreas Kindmark MD, PhD,
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Anders Rönnblom MD, PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Uppsala University Department of Medical Sciences, Uppsala SE-751 85, SwedenSearch for more papers by this authorGunilla Englund PhD
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorAnnica Jacobson PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorFredrik Rorsman MD, PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorPer Artursson PhD
Department of Pharmacy, Uppsala University, Uppsala, Sweden
Search for more papers by this authorAndreas Kindmark MD, PhD,
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Search for more papers by this authorCorresponding Author
Anders Rönnblom MD, PhD
Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Uppsala University Department of Medical Sciences, Uppsala SE-751 85, SwedenSearch for more papers by this authorAbstract
Background: Efflux transport proteins are important components of the intestinal barrier against bacterial toxins, carcinogens, and drugs. This investigation was conducted to determine the expression of Breast Cancer Resistance Protein (BCRP/ABCG2), P-glycoprotein (Pgp/MDR1/ABCB1), and Multidrug Resistance Protein 2 (MRP2/ABCC2) in the gut mucosa of patients with ulcerative colitis (UC).
Methods: Patients were thoroughly diagnosed according to well-established clinical, endoscopic, and histologic criteria to be included in the group of patients with active UC (n = 16) or UC in remission (n = 17). Colonic and rectal mucosa from patients with UC were compared with tissues from control subjects (n = 15). The mRNA expression (TaqMan) of the efflux transporters and the proinflammatory cytokines interleukin (IL)-1β and IL-6 was determined. Western blot was used in the analysis of protein expression and the tissue localization of BCRP was determined with confocal microscopy.
Results: BCRP and Pgp expression was strongly reduced in individuals with active inflammation compared with controls and was negatively correlated with the levels of IL-6 mRNA. The BCRP staining of colonic epithelium seen in healthy mucosa was diminished in inflamed tissues, with concurrent disruption of epithelial F-actin structure.
Conclusions: Two of the efflux transporters of importance for the barrier function of the gut mucosa, Pgp and BCRP, are expressed at strongly reduced levels during active inflammation in patients with UC. Investigations are warranted to determine whether the low levels of efflux transporters during active UC contribute to altered transport and tissue exposure of carcinogens, bacterial toxins, and drugs.
(Inflamm Bowel Dis 2007)
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