Maintained expression of alternative bile salt excretion pathways in inflammatory cholestasis in mice by treatment with class II nuclear hormon receptor ligands

Aims: Expression of hepatic organic anion transporters including basolateral overflow systems such as Mrp3 and Mrp4 is decreased during inflammatory cholestasis by experimental treatment with endotoxin (LPS). This crucial event putatively occurs by a cytokine-induced nucleocytoplasmic shift of RXR, the obligate heterodimerization partner of transactivating class II nuclear hormon receptors (NHR), as a central mechanism. We hypothesized that treatment with specific ligands of RXR and CAR may induce a redistribution of these receptors and subsequently a maintained transporter gene expression. Methods: Male C57/BL6…