Interleukin-6 down regulates the expression of transcripts encoding cytochrome P450 IA1, IA2 and IIIA3 in human hepatoma cells.
Effects of human interleukin-6 (hIL-6), the major acute phase inducer, on the expression of transcripts encoding cytochrome P450s were examined in human hepatoma-derived cells. Using reverse-transcription polymerase chain reaction, it was demonstrated that three hepatoma cell lines, HepG2, HepG2f and Hep3B, express P450 mRNAs encoding IA1, IA2 and IIIA3, the major P450 isozymes involved in carcinogen metabolism, and that they also show induction responses to treatment with their specific inducers. When hepatoma cells were treated with hIL-6, the levels of IA1, IA2 and IIIA3 mRNAs were markedly suppressed. These findings suggest that significant down regulation of cytochrome P450s may occur during the acute phase reaction, which may result in alterations in drug biotransformation.
Fukuda
Y
Y
Rockefeller University, New York, N.Y. 10021.
Ishida
N
N
Noguchi
T
T
Kappas
A
A
Sassa
S
S
D001483:Base Sequence; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015850:Interleukin-6 / Q000494:pharmacology*; D008113:Liver Neoplasms; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010088:Oxidoreductases / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase; D014158:Transcription, Genetic / Q000187:drug effects*
D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019388:Cytochrome P-450 CYP1A2; D012194:RNA-Directed DNA Polymerase