Glucocorticoid stimulates hepatitis B viral gene expression in cultured human hepatoma cells.
Glucocorticoids have been shown to influence the severity of hepatitis B virus-related chronic hepatitis in human. However, very little is known about the effects of glucocorticoids on hepatitis B virus replication in vitro. In this report, we used a well-differentiated human hepatoma cell line, Hep3B, transfected with hepatitis B virus complementary DNA as a model to show that a glucocorticoid analog, dexamethasone, can directly stimulate the production of HBsAg and HBeAg. Elevation of 3.5-kb pregenomic RNA and all other viral RNAs in the transfected Hep3B cells after dexamethasone treatment supports the hypothesis that glucocorticoids directly stimulate hepatitis B virus gene expression in vitro. The concentration of dexamethasone for its half-maximal stimulatory activity toward HBsAg, HBeAg and all viral transcripts was approximately 10(-8) mol/L, close to the affinity of glucocorticoid receptors to [3H]-triamcinolone acetonide in Hep3B cells (approximately 10(-8) mol/L). Specific glucocorticoid antagonist RU38486 completely blocked dexamethasone-induced HBV gene expression, suggesting that the stimulatory effect of dexamethasone was mediated through specific glucocorticoid receptors.
Chou
C K
CK
Department of Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Wang
L H
LH
Lin
H M
HM
Chi
C W
CW
D006528:Carcinoma, Hepatocellular; D003600:Cytosol / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014222:Triamcinolone Acetonide / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D014222:Triamcinolone Acetonide