EFFECTS OF BILE-ACIDS AND CHOLESTASIS ON MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I IN HUMAN AND RAT HEPATOCYTES

Background/Aims: Major histocompatibility complex (MHC) class I molecules, which are normally poorly expressed on the surface of hepatocytes, are overexp-ressed during cholestasis. The mechanisms responsible for this overexpression were examined. Methods: The expression of class I molecules, assessed by flow cytofluorimetry, and the class I messenger RNA (mRNA) transcripts, assessed by Northern blot analysis, were measured on normal human hepatocytes in primary culture. Results: Chenodeoxycholic acid induced an overexpression of MHC class I molecules, whereas ursodeoxycholic acid did not. The level of class I mRNA closely reflected that of the membrane protein. Moreover, cholestasis, induced in the rat by ligation-section of the common bile duct, increased the MHC class I mRNA level. Actinomycin D inhibited bile acid-induced class I transcription of rat hepatocytes in primary culture, whereas cycloheximide did not. Finally, class I mRNA expression was induced in hepatocytes by phorbol myristate acetate and by forskolin. This hyperexpression, as well as that observed with cheno-deoxycholic acid, was suppressed by an inhibitor of protein kinase C and protein kinase A. Conclusions: Taken together, these results suggest that chenodeoxycholic acid, as Interferon, activates protein kinase C and protein kinase A, resulting in the induction of MHC class I expression. © 1994.