Mechanisms of CYP3A Induction by Glucocorticoids in Human Fetal Liver Cells

• MATSUNAGA Tamihide

  Department of Pharmacy, Shinshu University Hospital Department of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Nagoya City University

• MARUYAMA Masataka

  Department of Pharmacy, Fujimi Kogen Hospital Department of Pharmacy, Shinshu University Hospital

• MATSUBARA Tsutomu

  Department of Anatomy, Graduate School of Medicine, Osaka City University Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University

• NAGATA Kiyoshi

  Division of Environmental Health, Tohoku Pharmaceutical University

• YAMAZOE Yasushi

  Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University

• OHMORI Shigeru

  Department of Pharmacy, Shinshu University Hospital

Abstract

Human fetal liver (HFL) cells express major drug metabolic enzymes CYP3A4, CYP3A5 and CYP3A7. In the fetal hepatocytes, betamethasone and dexamethasone (DEX) markedly enhanced the expression levels of CYP3A4 and CYP3A7 mRNAs and slightly increased the expression level of CYP3A5 mRNA. Interestingly, a high correlation between the CYP3A induction ability and the intensity of anti-inflammatory effect was observed. Human glucocorticoid receptor (GR)–small interfering RNA clearly attenuated the expression level of GR mRNA, and diminished the DEX-stimulated CYP3A4, CYP3A5 and CYP3A7 expression in HFL cells. These findings indicate that GR mediates the induction of CYP3A4 and CYP3A7 expression in human fetal hepatocytes as well as the CYP3A5.<br>

Journal

• Drug Metabolism and Pharmacokinetics

  Drug Metabolism and Pharmacokinetics 27 (6), 653-657, 2012

  The Japanese Society for the Study of Xenobiotics

Keywords

• CYP3A
• induction
• glucocorticoid
• human fetal liver cells
• glucocorticoid receptor
• small interfering RNA
• specific small interfering RNA

Details

• CRID: 1390001205179640832
• NII Article ID: 130004933510
• NII Book ID: AA1162652X
• DOI: 10.2133/dmpk.dmpk-12-nt-018
• COI: 1:CAS:528:DC%2BC3sXit1Sksbs%3D
• ISSN: 18800920
• ISSN: 13474367
• HANDLE: 10091/17641
• PubMed: 22673009
• Web Site: https://soar-ir.repo.nii.ac.jp/records/8028
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715305383?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1347436715305383?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2013276274
• Text Lang: en
• Data Source:
  • JaLC
  • IRDB
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed