Effects of bile acids and cholestasis on major histocompatibility complex class I in human and rat hepatocytes.
OBJECTIVE
Major histocompatibility complex (MHC) class I molecules, which are normally poorly expressed on the surface of hepatocytes, are overexpressed 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 chenodeoxycholic 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.
Hillaire
S
S
Unité d'Hépatologie, Hôpital Saint-Antoine, Paris, France.
Boucher
E
E
Calmus
Y
Y
Gane
P
P
Ballet
F
F
Franco
D
D
Moukthar
M
M
Poupon
R
R
D000328:Adult; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002779:Cholestasis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004789:Enzyme Activation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D001647:Bile Acids and Salts; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger; D002635:Chenodeoxycholic Acid; D003513:Cycloheximide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C