g., bilirubin) into bile canaliculus [11, 12]. The effect of MRP2 is regulated at transcriptional and posttranscriptional levels in response both to many endogenous and
xenobiotic substances and to abnormal states, such as biliary obstruction and inflammation [17, 18]. Biliary obstruction initiates marked changes in transporter expression, which is reasonable for hepatic protection [19]. Basolateral transporters Staurosporine in vivo for bile acid uptake are downregulated to prevent further uptake, and the canalicular export pump, MRP2, is also downregulated. Alternatively, basolateral transport systems such as MRP3 and 4 are compensatively upregulated to prevent accumulation of potentially toxic substrates in hepatocytes [20]. Secretion of interleukin-1β (IL-1β) induced by obstructive cholestasis is responsible for reduced transcription of MRP2 via decreased binding RXRα to the MRP2 promoter [21, 22]. Meanwhile, inflammatory status induced BIBW2992 by proinflammatory cytokines, including tumor necrosis factor α, IL-1β, and IL-6, also results in reduced bile flow
via changing gene expression of transporters [23, 24]. MRP2 expression is downregulated drastically in cytokinemia induced by endotoxin administration [25–27]. In addition, MRP2 expression level in the BA liver was reported to be downregulated compared with age-matched controls that had non-cholestatic liver diseases [28]. In the present study, we found no significant difference of MRP2 expression between BA and control. Our result might Phosphatidylinositol diacylglycerol-lyase be influenced by selection of controls; the average age of controls was much older than that of BA patients. Considering the age dependency of canalicular transporters, including MRP2 especially in small infants [17], the difference of ages might have
affected the results. Furthermore, the controls include liver samples from choledochal cyst, potentially an obstructive cholestatic disease, although the cases of choledochal cyst that had jaundice at the sampling were excluded in the study. The pathoselleck chemicals physiology of BA is characterized as inflammatory obliterative cholangiopathy [1]. Immunohistochemical studies have revealed that activated T cells infiltrate the periductal area with expression of various intracellular adhesion molecules [29, 30]. In the present study, we showed that a higher hepatic MRP2 expression level at the time of surgery resulted in faster clearance of jaundice with lower serum levels of bilirubin within a month of surgery. It is still unclear what caused difference of MRP2 expression in the BA liver. Considering the molecular mechanisms of bile physiology, prolonged biliary obstruction and/or advanced inflammatory status might have effect on it, but further studies are still necessary. Meanwhile, the level of MRP2 expression was not involved in long-term prognosis. The discrepancy between clearance of jaundice and prognosis could be partially explained by a small number of cases.