Mechanisms of IFN-gamma induction by natural killer cell stimulatory factor (NKSF/IL-12). Role of transcription and mRNA stability in the synergistic interaction between NKSF and IL-2.
We have investigated the molecular mechanisms regulating IFN-gamma production in human T lymphocytes stimulated by NK cell stimulatory factor (NKSF/IL-12). We show that NKSF synergizes with IL-2 and phorbol diesters inducing the accumulation of IFN-gamma mRNA in PHA-activated T cell blasts. NKSF regulates IFN-gamma mRNA expression in PHA blasts and the T leukemia cell line, TALL-103/2, at both the transcriptional and posttranscriptional levels. NKSF increases the transcriptional rate for IFN-gamma in both these cell types, as determined by nuclear run-on analysis. However, synergy between NKSF and IL-2 can be demonstrated only at the level of mRNA stability, and both cytokines are required to increase IFN-gamma mRNA half-life.
Chan
S H
SH
Wistar Institute, Philadelphia, PA 19104.
Kobayashi
M
M
Santoli
D
D
Perussia
B
B
Trinchieri
G
G
D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D007378:Interleukins; D012333:RNA, Messenger; D018664:Interleukin-12; D007371:Interferon-gamma; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate