The role of reactive oxygen metabolites in the transcriptional regulation of IFN-gamma gene expression by histamine in NK cells following IL-2 stimulation.
The secretion of interferon-gamma (IFN-gamma) by natural killer (NK) cells following in vitro stimulation with interleukin-2 (IL-2) is inhibited by co-incubation with autologous monocytes at a transcriptional level by more than sixty-fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN-gamma was operating at a pre-translational level, this was indicated by the inability of CD 56(+)-enriched natural killer cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN-gamma production. We thereby conclude that histamine behaves synergistically with IL-2 at a transcriptional level to induce IFN-gamma even in an admixture of NK cells and monocytes.
Houze
T A
TA
Ostra Hospital, Molecular Oncology Laboratory, Gothenborg, Sweden.
Larsson
P A
PA
Hellstrand
K
K
Gustavsson
B
B
D001483:Base Sequence; D002374:Catalase / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017931:DNA Primers; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D006632:Histamine; D007371:Interferon-gamma; D002374:Catalase