Wilder J A, Yuan D
University of Texas Southwestern Medical Center, Department of Pathology, Dallas 75235, USA.
Int Immunol. 1995 Apr;7(4):575-82. doi: 10.1093/intimm/7.4.575.
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.
我们之前报道过，大型的、可能在体内被激活的B细胞会刺激小鼠自然杀伤（NK）细胞分泌更高水平的干扰素-γ。为了进一步了解干扰素-γ诱导的机制，我们比较了用B淋巴细胞或佛波酯肉豆蔻酸酯（PMA）+离子霉素刺激NK细胞后干扰素-γ mRNA产生的调控情况。在此我们表明，两种刺激物刺激NK细胞均会导致干扰素-γ mRNA增加，尽管动力学不同。虽然诱导需要新的RNA合成，但我们在刺激后未检测到干扰素-γ基因转录增加。在干扰素-γ mRNA积累后测量mRNA降解速率表明，这种mRNA比未刺激的NK细胞产生的干扰素-γ mRNA更稳定。总之，这些结果表明，B细胞或PMA+离子霉素刺激的NK细胞中干扰素-γ mRNA和蛋白质的增加是由于已有干扰素-γ信使的稳定化。我们的结果还表明，稳定mRNA的因子的诱导，尽管目前尚不清楚，但需要新的RNA合成。
