[Regulation of hepatobiliary transporters in cholestatic liver disease].

Bile formation essentially depends on hepatobiliary organic anion transporters, which are exclusively localized either to the sinusoidal or canalicular membrane. Cloning of their genes has elucidated the pathophysiology of both hereditary and acquired forms of cholestasis. The regulation of these transporter genes occurs either by ubiquitous nuclear hormone receptors, which are activated by ligands including xenobiotics and bile acids, or by hepatocyte-specific trans-activators. Proinflammatory cytokines such as tumor necrosis factor alpha and interleukin-1beta represent additional mediators. Understanding of these regulatory pathways represents a mandatory prerequisite for any future therapeutic intervention in acute or chronic liver diseases.