Regulation of IFN-γ mRNA production in murine natural killer cells

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Abstract
We have previously reported that large, presumably in vivo activated, B cells stimulate murine natural killer (NK) cells to secrete increased levels of IFN-γ. In order to further understand the mechanism of IFN-γ Induction, we compared the regulation of IFN-γ 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 in an increase in IFN-γ mRNA, albeit with different kinetics. Although the Induction requires new RNA synthesis, we could not detect increased transcription of the IFN-γ gene after stimulation. Measurement of the rate of mRNA degradation after IFN-γ mRNA has accumulated demonstrates that this mRNA is more stable than IFN-γ mRNA from unstimulated NK cells. Together, these results suggest that the increase in IFN-γ mRNA and protein in NK cells, stimulated by B cells or PMA + ionomycin, results from stabilization of pre-existing IFN-γ message. Our results also suggest that induction of the factor which stabilizes the mRNA, although as yet unknown, requires new RNA synthesis.

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