Towards treatment of cholestatic liver disease in children via interference with transcriptional regulation of hepatic transport systems

Inflammation-induced cholestasis (IIC) is a frequently occurring phenomenon. A central role in its pathogenesis is played by nuclear receptors (NRs). These ligandactivated transcription factors not only regulate basal expression of hepatobiliary transport systems, but also mediate adaptive responses to inflammation and possess anti-inflammatory characteristics. The latter two functions may be exploited in the search for new treatments for IIC as well as for cholestasis in general. Current knowledge of the pathogenesis of IIC and the dual role NRs in this process are reviewed. Special interest is given to the use of NRs as potential targets for intervention.