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Chenodeoxycholic acid-dependent induction of major histocompatibility complex class I mRNA expression in a human
1Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Abstract:
Primary biliary cirrhosis is known as an autoimmune chronic cholestatic disease and characterized by various immunological abnormalities. Especially, the aberrant expression of major histocompatibility complex (MHC) class I antigens on hepatocytes has been considered to have a pivotal role in the pathogenesis and progression of the disease. However, the underlying mechanism of this aberrant expression of MHC class I molecules has not yet been clarified. In the present study we showed that MHC class I immunoreactivities were increased by treatment with chenodeoxycholic acid (CDCA) in the human hepatoma cell line HLE. Moreover, CDCA treatment of the cells increased the steady-state levels of MHC class I mRNA. Since CDCA is one of major constituents of endogenous bile acids in cholestasis, these results suggest that intrahepatic cholestasis, which is almost inevitably associated with PBC, increases both production and surface expression of MHC class I antigens in hepatocytes.