Inhibition of interferon-gamma- and phorbol ester-induced HLA-DR and interleukin-1 production by the expression of a transfected poly(ADP-ribose) synthetase gene in human leukemia THP-1 cells.
We have examined a correlation between an expression level of poly(ADP-ribose) synthetase gene and the stage of monocytic differentiation. We selected three human leukemia cell lines, U937, THP-1, and J111, whose differentiation stage was characterized by nitroblue tetrazolium reduction activity, non-specific esterase activity, phagocytic activity and a cell surface marker. Enzyme activity and mRNA level of the synthetase decreased in accompaniment with the progress of monocytic differentiation. When THP-1 cells were treated with either interferon-gamma or phorbol ester, mRNA level of the synthetase decreased and HLA-DR or interleukin-1 was induced, respectively. We transfected expression plasmid of the exogenous synthetase gene to examine whether the down-regulation of the synthetase is a necessary step to induce these proteins. An expression of the exogenous synthetase gene inhibited the interferon-gamma- and phorbol ester-dependent induction of HLA-DR and interleukin-1. The results suggest that down-regulation of the synthetase may be a signal mediator of immunological response such as HLA-DR or interleukin-1 production in monocytes.
Tomoda
T
T
Department of Pediatrics, Kochi Medical School, Japan.
Kurashige
T
T
Taniguchi
T
T
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics*; D007700:Kinetics; D007948:Leukemia, Monocytic, Acute; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D010587:Phagocytosis / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014162:Transfection
D006684:HLA-DR Antigens; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007371:Interferon-gamma; D011065:Poly(ADP-ribose) Polymerases; D013755:Tetradecanoylphorbol Acetate