Immunomodulation of HLA class I and II expression on a human tumor derived cell line by 5-azacytidine, bacterial lipopolysaccharide, gamma interferon and a phorbol ester.
The modulation of histocompatibility antigens (HLA) expression by four different agents (gamma-IFN, LPS, PMA and 5-azaC) was investigated on a human tumor derived cell line that did not constitutively express HLA class I and class II molecules on its surface. Demethylating drug 5-azaC induced HLA class I but not HLA class II antigen expression. Gamma interferon and LPS induced HLA-DR and HLA-DP, but not HLA-DQ class II nor HLA class I antigens, while phorbol ester was unable to induce either class I or II molecule expression of the HLA system. These results suggest that HLA class I expression is constitutively inhibited by methylation of its coding genes. Treatment with 5-azaC leads to the HLA class I molecule expression, while HLA class II genes, DR and DP, seem to be under a different inhibitory mechanism as it was induced by LPS and gamma-interferon but not by 5-azaC. HLA-DQ class II antigens were not detected in response to any of the immunomodulators used.
Santamaría
M
M
Immunology Unit, Reina Sofía Hospital, Spain.
Muñoz
E
E
Molina
I
I
Ortega
C
C
Peña
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology; D001374:Azacitidine / Q000494:pharmacology*; D006680:HLA Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006680:HLA Antigens; D006683:HLA-DQ Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D001374:Azacitidine; D013755:Tetradecanoylphorbol Acetate