Regulation of the major histocompatibility complex class I mRNA expression by bile acids in cultured human hepatoma cells.
We investigated the effect of bile acids on major histocompatibility complex (MHC) class I gene expression in the cultured human hepatoma cell HepG2. Not only chenodeoxycholic acid, but its stereoisomer ursodeoxycholic acid as well, increased steady state level of MHC class I mRNA. When various bile acids were studied, inducibility of MHC class I mRNA was closely associated with the hydrophobicity of the corresponding bile acids. Pretreatment of the cells with a protein kinase C (PKC) inhibitor H7 suppressed induction of MHC class I mRNA by those bile acids. Furthermore, treatment of the cells with chenodeoxycholic acid significantly induced translocation of PKC from cytosol to membrane. In summary, our data strongly indicate up-regulatory effect of bile acids on MHC class I mRNA expression, most probably via activation of PKC-dependent pathway.
Hirano
F
F
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Tanaka
H
H
Makino
Y
Y
Okamoto
K
K
Inaba
M
M
Miura
T
T
Makino
I
I
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001647:Bile Acids and Salts / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D001647:Bile Acids and Salts; D015395:Histocompatibility Antigens Class I; D007546:Isoquinolines; D010879:Piperazines; D012333:RNA, Messenger; D002635:Chenodeoxycholic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate