OKANO Teruo    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Induction of drug-metabolizing enzymes by phenobarbital in layered co-culture of a human liver cell line and endothelial cells.
Journal	Formal name：Biological & pharmaceutical bulletin Abbreviation：Biol Pharm Bull ISSN code：(0918-6158)0918-6158(Linking)
Domestic / Foregin	Foregin
Volume, Issue, Page	32(5),pp.813-7
Author and coauthor	Ohno Maki†, Motojima Kiyoto, Okano Teruo, Taniguchi Akiyoshi*
Publication date	2009/05
Summary	Primary human hepatocytes are extensively used to study the potential of drugs to induce cytochrome P450 (CYP). However, the activities of these enzymes decrease rapidly during culture. Previously we reported that in a layered co-culture system with HepG2 and bovine endothelial cells, the expression levels of various CYP genes were significantly increased compared with the monolayer cultured HepG2 cells. Here, we examined the induction of CYP gene expression by an inducer by examining the effect of phenobarbital treatment on CYP gene expression in the co-culture system. In the layered co-cultured HepG2, expression of the CYP2C and CYP3A family genes was induced by phenobarbital treatment. We also detected CYP3A4 enzyme induction using this co-culture system. Moreover, the induction of hepatic drug transporters by phenobarbital was detected. These results suggest that functional regulation of the CYP and transporter gene pathway is retained in these layered co-cultured cells. Thus, this system may serve as a useful model for in vitro pharmacological studies on the coordinated regulation of transport and metabolism.
DOI	10.1248/bpb.32.813
PMID	19420747