Glucocorticoid stimulates hepatitis B viral gene expression in cultured human hepatoma cells

✍ Scribed by Chen-Kung Chou; Li-Hsien Wang; Hsing-Mei Lin; Chin-Wen Chi

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 719 KB
• Volume: 16
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840160104

✦ Synopsis

Glucocorticoids

have been shown to inhence the severity of hepatitis B virugrelated 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 welldifferentiated human hepatoma cell line, Hep3B, transfected with hepatitis B virus complementary DNA as a model to show that a glucocorticoid analog, dexamethaeone, can directly stimulate the production of HBsAg and HBeAg. Elevation of 3.6-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 mol/L, close to the affinity of glucocorticoid receptors to PHItriamcinolone acetonide in Hep3B cells ( -lop8 mom). Specific glucocorticoid antagonist RU38486 completely blocked dexamethasone-induced HBV gene expression, suggesting that the stimulatory effect of dexamethaeone was mediated through specific glucocorticoid receptors. (HEPATOLOGY 1992;16:13-18.)

HBV is a small, partially double-stranded circular DNA virus that causes acute and chronic hepatitis in humans. The virus is strongly associated with development of HCC in humans and woodchucks (1). The observations of activation of latent infection (21, increasing levels of HBV markers (3) and increasing severity of liver disease (4) on glucocorticoid therapy in patients with HBV-related chronic hepatitis suggest that glucocorticoids influence HBV replication and gene expression in uiuo.

The specific glucocorticoid response element in the HBV genome was demonstrated when it was introduced into the plasmid containing the simian virus 40 early