Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone.
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.
Wakui
Yuta
Y
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aobaku, Sendai 980-8574, Japan.
Inoue
Jun
J
Ueno
Yoshiyuki
Y
Fukushima
Koji
K
Kondo
Yasuteru
Y
Kakazu
Eiji
E
Obara
Noriyuki
N
Kimura
Osamu
O
Shimosegawa
Tooru
T
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D006509:Hepatitis B / Q000188:drug therapy; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D047495:PPAR gamma / Q000819:agonists*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D016898:Interferon-alpha; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019259:Lamivudine