Decreased PXR and CAR inhibit transporter and CYP mRNA Levels in the liver and intestine of mice with collagen-induced arthritis.

Nuclear receptors, such as pregnane X receptor (PXR) and constitutive androstane receptor (CAR), regulate the transcription of transporters and cytochrome P450s (CYPs). We investigated whether quantitative and functional changes in PXR and CAR affected the transporters and CYPs in a mouse model of chronic arthritis. The mRNA levels of PXR were significantly decreased in the intestine of mice with collagen-induced arthritis (CIA) compared with control mice. The mRNA levels of CAR were significantly decreased in both the liver and intestine of CIA mice. The mRNA levels of Mdr1a/1b, Mrp3, BCRP and Cyp2b10 were decreased in the liver of CIA mice, while little change in the mRNA levels was observed for Cyp3a11 in the liver and the transporters in the intestine. Taken together, the present results reveal that the effects of CAR mRNA suppression on the regulation of transporters and CYPs differ between the liver and intestine in chronic arthritis.