Espinoza-Delgado I, Longo D L, Gusella G L, Varesio L
Immunobiology Section, National Cancer Institute, Frederick Cancer Research Development Center, MD 21702-1201.
J Immunol. 1992 Nov 1;149(9):2961-8.
We investigated the effects of IFN-gamma and IL-2 on IL-2R alpha and beta mRNA expression in human monocytes. Low basal expression of IL-2R beta mRNA was detected in fresh monocytes. Stimulation of monocytes with IL-2 induced a significant increase of IL-2R beta mRNA, but did not induce IL-2R alpha mRNA. In contrast, stimulation of monocytes with IFN-gamma-induced IL-2R alpha mRNA, but did not modify IL-2R beta mRNA. Five U/ml of IFN-gamma induced IL-2R alpha mRNA and 2.2 nM of IL-2 induced IL-2R beta mRNA, both within 3 h. Nuclear run-on experiments demonstrated that the induction of IL-2R alpha mRNA by IFN-gamma is controlled, at least in part, at the transcriptional level. In contrast, the enhancement of IL-2R beta mRNA by IL-2 is controlled at a posttranscriptional level and is associated with an increase in the half-life of IL-2R beta mRNA. The results of studies on the cytotoxic activity and on the expression of c-fms mRNA of monocytes activated by the combination of IFN-gamma and IL-2 show that pretreatment with IFN-gamma renders monocytes more sensitive to activation by IL-2. These results demonstrate that the IL-2R alpha and IL-2R beta subunits are induced by different lymphokines through distinct mechanisms and that both receptor subunits can influence the response of monocytes to IL-2.
我们研究了干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）对人单核细胞中IL-2Rα和β mRNA表达的影响。在新鲜单核细胞中检测到IL-2Rβ mRNA的基础表达较低。用IL-2刺激单核细胞可导致IL-2Rβ mRNA显著增加，但不诱导IL-2Rα mRNA。相反，用IFN-γ刺激单核细胞可诱导IL-2Rα mRNA，但不改变IL-2Rβ mRNA。5 U/ml的IFN-γ和2.2 nM的IL-2均可在3小时内诱导IL-2Rα和IL-2Rβ mRNA表达。细胞核连续转录实验表明，IFN-γ对IL-2Rα mRNA的诱导至少部分是在转录水平上控制的。相比之下，IL-2对IL-2Rβ mRNA的增强作用是在转录后水平控制的，并且与IL-2Rβ mRNA半衰期的延长有关。关于IFN-γ和IL-2联合激活的单核细胞的细胞毒性活性和c-fms mRNA表达的研究结果表明，用IFN-γ预处理可使单核细胞对IL-2的激活更敏感。这些结果表明，IL-2Rα和IL-2Rβ亚基由不同的淋巴因子通过不同的机制诱导，并且两个受体亚基均可影响单核细胞对IL-2的反应。
