Mechanisms of oxysterol-induced disease: insights from the biliary system.

Oxysterols are oxidized species of cholesterol that are derived from exogenous (e.g. dietary) and endogenous (in vivo) sources. Oxysterols play critical roles in normal physiologic functions as well as in pathophysiologic processes in a variety of organ systems. This review provides an overview of oxysterol biology from the vantage point of the biliary system. Several oxysterols have been identified in human bile in the context of biliary tract infection and inflammation. This finding has led to investigations regarding the potential pathophysiologic significance of biliary oxysterols in diseases affecting the biliary system, with an emphasis on cholangiocarcinoma. Emerging evidence implicates specific oxysterols in the development and progression of this malignancy. This review will summarize the literature on oxysterols in the biliary system and discuss how the accumulated evidence contributes to a hypothesis describing the molecular basis of cholangiocarcinogenesis.