Hirano F, Tanaka H, Makino I
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Biochem Biophys Res Commun. 1993 Sep 30;195(3):1408-14. doi: 10.1006/bbrc.1993.2200.
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.
原发性胆汁性肝硬化是一种自身免疫性慢性胆汁淤积性疾病,其特征为多种免疫异常。特别是,肝细胞上主要组织相容性复合体(MHC)I类抗原的异常表达被认为在该疾病的发病机制和进展中起关键作用。然而,MHC I类分子这种异常表达的潜在机制尚未阐明。在本研究中,我们发现用鹅去氧胆酸(CDCA)处理人肝癌细胞系HLE后,MHC I类免疫反应性增加。此外,CDCA处理细胞增加了MHC I类mRNA的稳态水平。由于CDCA是胆汁淤积时内源性胆汁酸的主要成分之一,这些结果表明几乎不可避免地与原发性胆汁性肝硬化相关的肝内胆汁淤积会增加肝细胞中MHC I类抗原的产生和表面表达。