Hepatic YB–1 activation occurs by different mechanisms and mediates Mrp2 suppression and MMP–2 induction during endotoxemia

Aim: Expression of hepatobiliary transporters is decreased during inflammatory cholestasis. Reduction of Mrp2 is mediated by IL–1ß-dependent signals but the underlying mechanism is still unclear. YB–1 is a predominantly cytoplasmic protein which translocates to the nucleus in response to various insults and has previously been characterized as a transcriptional repressor of rat Mrp2 and inductor of MMP–2. Consequently, we characterized the role of YB–1 as a suppressor of hepatic negative acute phase genes such as Mrp2. Methods: Rats were i.p. injected with LPS and livers harvested after 20 hours. Liver sections…