Effect of Interferon on the Production of HBsAg and Induction of an Antiviral State in Human Hepatoma Cell Line PLC/PRF/5

Abstract

The effects of human a and fJ interferons (IFN) on the production of HBsAg by PLCjPRF/5 cells, an HBsAg-producing human hepatoma cell line, were studied in the exponential and stationary phases of cell growth. When exponential phase cells were treated with 100 or 1,000 U of IFN per ml for 48 hr, the amount of HBsAg in the culture medium decreased. The number of cells and the synthesis of DNA and proteins were also reduced by the IFN treatment. These results suggested that IFN did not affect the production of HBsAg specifically in exponential phase cells. When cells in the stationary phase were similarly treated with IFN, HBsAg production was not inhibited nor did the number of cells decrease.To examine the antiviral state induced by IFN in PLCjPRF/5, induction of 2'5'-0Iigo(A) synthetase and susceptibility to two kinds of viruses were examined. The 2'5'-0Iigo(A) synthetase activity was increased in an IFN-dose dependent manner. Susceptibility to vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV) was decreased by treatment with 10 and 100 U of IFN per ml for 20 hr. It was concluded that IFN-a and IFN-fJ induce 2'5'-0Iigo(A) synthetase and the antiviral state, but do not inhibit HBsAg production by PLC/ PRF/5 cells.Interferon (IFN) is known for its therapeutic effect in several human viral infections. Recently, a number of reports have suggested certain effects of IFN in the treatment of chronic hepatitis B virus infection (9,12,13,18). IFN treatment reduces hepatitis B virus-specific DNA-polymerase activity and other viral markers in the serum of patients with chronic hepatitis (22). Several viral markers also disappear or decrease in hepatic tissue (21). Other workers, however, observed no effect of IFN treatment except for a transient decrease in DNA-polymerase activity (26). These conflicting results may be attributed to the differences in the amount and duration of IFN treatment given or in the immunological state of the Abbreviations: IFN, interferon; VSV, vesicular stomatitis virus; EMCV, encephalomyocarditis virus; TCIDso, 50% tissue culture infectious dose; MEM, Eagle's minimal essential medium. 705

A Cytotoxic Acetophenone with a Novel Skeleton, Isolated fromCynanchum taiwanianum

“…PLC/PRF/5 Cells were established from a human hepatoma and known to produce HBs Ag continuously in culture fluids [9]. Human hepatoma PLC/PRF/5 cells, epidermoid carcinoma KB cells, and human bladder carcinoma T-24 cells were maintained in Dulbeccos modified Eagle medium (DMEM, Gibco BRL, Grand Island, NY, USA) [7] [8], containing 10% fetal bovine serum (FBS, Gibco BRL), 2 mm l-glutamine, penicillin (100 units/ml) and streptomycin (100 mg/ml).…”

Cytotoxic Principles and Their Derivatives of Formosan Solanum Plants

“…Compound 3 was identified from physical and spectral data and by chemical reaction (2). (12), 138 (40), 99 (18), 98 (100), [a + H]+ 18 (17); fabms (positive mode) m/z (rel. int.…”

“…The CHC13 extract was concentrated, the residue was purified by chromatography on Si gel, and the eluate was recrystallized from a mixture of MeOH, CHC13, and Me2CO to give colorless needles, identified from physical and spectral data. Biological assay.-PLC/PRF/5 cells were established from human hepatoma and are known to produce hepatitis B surface antigen continuously in culture fluids (18). The cells were grown as continuous cultures in a growth medium consisting of Dulbecco's modified Eagle medium (DMEM, GIBCO, NY), 10% fetal bovine serum (FBS, GIBCO), 100 IU/ml streptomycin, 2 mM L-glutamine, and antibiotics.…”

“…screen.-Protective effects of isolated compounds and compound derivatives were evaluated for protection against CCl4-induced hepatotoxicity in ICR male mice (18-20 g) using 6-10 mice for each experiment. The protective effect was assessed by determination of SCOT and SGPT values (18), and liver damage was induced with a fresh mixture of equal volumes of CC14 and olive oil given in one injection in doses of 0.1 ml/kg of CC14 by the ip route. The test compound was administered and experiments conducted as described in Lin and Gan (1).…”

“…The nmr spectra of 4 acetate also supported structure 4. The protective effect of khasianine (3), dihydrosolasodine (the reduced product of solasodine), capsimine, and 1 against CCl4-induced hepatic damage, and the cytotoxic effects ofN-methylsolasodine, capsimine, sol- asonine (4), narigenin, etioline (5), and capsicastrine (5) against human PLC/PRF/5 and KB cells in vitro (18,19) were studied and the results were listed in Tables 2 and 3, respectively. Khasianine, dihydrosolasodine, capsimine, and 1 exhibited strong activity against liver damage induced by CCI4.…”