Regulation of IFN-gamma mRNA production in murine natural killer cells.
We have previously reported that large, presumably in vivo activated, B cells stimulate murine natural killer (NK) cells to secrete increased levels of IFN-gamma. In order to further understand the mechanism of IFN-gamma induction, we compared the regulation of IFN-gamma mRNA production after stimulation of NK cells with either B lymphocytes or phorbol myristate acetate (PMA)+ionomycin. Here we show that stimulation of NK cells by either stimuli results increase in IFN-gamma mRNA, albeit with different kinetics. Although the induction requires new RNA synthesis, we could not detect increased transcription of the IFN-gamma gene after stimulation. Measurement of the rate of mRNA degradation after IFN-gamma mRNA has accumulated demonstrates that this mRNA is more stable than IFN-gamma mRNA from unstimulated NK cells. Together, these results suggest that the increase in IFN-gamma mRNA and protein in NK cells, stimulated by B cells or PMA+ionomycin, results from stabilization of pre-existing IFN-gamma message. Our results also suggest that induction of the factor which stabilizes the mRNA, although as yet unknown, requires new RNA synthesis.
Wilder
J A
JA
University of Texas Southwestern Medical Center, Department of Pathology, Dallas 75235, USA.
Yuan
D
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D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006207:Half-Life; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D007376:Interleukin-2 / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000378:metabolism*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D012333:RNA, Messenger / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D007376:Interleukin-2; D012333:RNA, Messenger; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate