Document Detail

Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone.
MedLine Citation:
PMID:  20430009     Owner:  NLM     Status:  MEDLINE    
Although chronic infection of hepatitis B virus (HBV) is currently managed with nucleot(s)ide analogues or interferon-alpha, the control of HBV infection still remains a clinical challenge. Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor, that plays a role in glucose and lipid metabolism, immune reactions, and inflammation. In this study, the suppressive effect of PPAR ligands on HBV replication was examined in vitro using a PPARalpha ligand, bezafibrate, and a PPARgamma ligand, rosiglitazone. The effects were examined in HepG2 cells transfected with a plasmid containing 1.3-fold HBV genome. Whereas bezafibrate showed no effect against HBV replication, rosiglitazone reduced the amount of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen in the culture supernatant. Southern blot analysis showed that the replicative intermediates of HBV in the cells were also inhibited. It was confirmed that GW9662, an antagonist of PPARgamma, reduced the suppressive effect of rosiglitazone on HBV. Moreover, rosiglitazone showed a synergistic effect on HBV replication with lamivudine or interferon-alpha-2b. In conclusion, this study showed that rosiglitazone inhibited the replication of HBV in vitro, and suggested that the combination therapy of rosiglitazone and nucleot(s)ide analogues or interferon could be a therapeutic option for chronic HBV infection.
Yuta Wakui; Jun Inoue; Yoshiyuki Ueno; Koji Fukushima; Yasuteru Kondo; Eiji Kakazu; Noriyuki Obara; Osamu Kimura; Tooru Shimosegawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  396     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-07-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  508-14     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier Inc. All rights reserved.
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan.
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MeSH Terms
Antiviral Agents / pharmacology*,  therapeutic use
Drug Therapy, Combination
Hepatitis B / drug therapy
Hepatitis B virus / drug effects*,  genetics
Interferon-alpha / pharmacology,  therapeutic use
Lamivudine / pharmacology,  therapeutic use
PPAR gamma / agonists*
Thiazolidinediones / pharmacology*,  therapeutic use
Virus Replication / drug effects*
Reg. No./Substance:
0/Antiviral Agents; 0/Interferon-alpha; 0/Ligands; 0/PPAR gamma; 0/Thiazolidinediones; 0/interferon-alpha 2; 122320-73-4/rosiglitazone; 134678-17-4/Lamivudine

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