Synergistic effect of 5-azacytidine and gamma-interferon or dimethyl sulfoxide on expression of HLA class I antigens by PLC-PRF-5 cells.
In order to elucidate the mechanism by which HLA antigens expression is induced or enhanced on the injured or transformed hepatocytes, we have made in vitro studies using human hepatic tumor-derived cell lines as a model system. In the present study, PLC-PRF-5 cells that have the integrated form of hepatitis B virus genome in DNA were treated with 5-azacytidine (5-azaC) in combination with gamma-interferon (IFN-gamma) or dimethyl sulfoxide (DMSO). HLA antigens on the cell surface were quantitated by using a modified cell-ELISA method. As a result, it was demonstrated that DMSO- or IFN-gamma-treatment enhanced expression of HLA class I antigens on the cell surface. In addition, enhanced expression of the antigens on PLC-PRF-5 cells treated with 5-azaC in combination with IFN-gamma or DMSO represented a synergistic effect of these inducers on HLA class I antigens expression although no changes in HLA antigens expression were induced after 5-azaC-treatment alone in short-term experiments. Furthermore, an indirect immunofluorescent analysis of hepatitis B surface antigen on the cells demonstrated increased expression of the antigen after 5-azaC-treatment alone. HLA class II antigens and hepatitis B core antigen were not induced even after those treatments and also not after a long-term experiment. These results might indicate possible modulation of HLA class I and hepatitis B virus antigens expression on the cultured cells by a DNA hypomethylating agent, 5-azaC.
Fukusato
T
T
Department of Pathology, Mount Sinai School of Medicine, New York, NY.
Mohamad
A
A
Gerber
M A
MA
Thung
S N
SN
D000911:Antibodies, Monoclonal; D001374:Azacitidine / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D006680:HLA Antigens / Q000032:analysis / Q000096:biosynthesis*; D006681:HLA-D Antigens / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008113:Liver Neoplasms; D011994:Recombinant Proteins / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D006681:HLA-D Antigens; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001374:Azacitidine; D004121:Dimethyl Sulfoxide