Nakanishi K, Matsui K, Hirose S, Yoshimoto T, Hiroishi K, Kono T, Hada T, Hamaoka T, Higashino K
Third Department of Internal Medicine, Hyogo College of Medicine, Japan.
J Immunol. 1990 Sep 1;145(5):1423-9.
IL-5 renders BCL1-CL-3 (CL-3) cells responsive to IL-2 by increasing the number of high affinity IL-2R, whereas IL-4 prohibits such action of IL-5 to prepare CL-3 cells responsive to IL-2. Here we have found that genes for p75kDa-IL-2R and p55kDa-IL-2R are differentially regulated by IL-4 and IL-5. Nonstimulated CL-3 cells constitutively express mRNA for p75kDa-IL-2R and p55kDa-IL-2R. IL-5 stimulation principally augments the expression of p75kDa-IL-2R mRNA (4- to 8-fold), although modestly increasing the expression of p55kDa-IL-2R mRNA. Kinetic studies have revealed a maximal increase in p75kDa-IL-2R mRNA expression at 12 h and a decline thereafter, substantiating our previous kinetic study of the expression of high affinity IL-2R after the IL-5 stimulation. By contrast, IL-4 stimulation modestly increases the expression of p75kDa-IL-2R mRNA, whereas markedly reducing the expression of p55kDa-IL-2R mRNA, irrespective of whether CL-3 cells were stimulated with IL-4 alone or together with IL-5 and IL-2. Moreover, addition of IL-4 into the culture containing IL-5 and IL-2 causes striking reduction in the level of J-chain mRNA, which otherwise is markedly induced by stimulation with IL-5 and IL-2. These results clearly illustrate the differential regulation of p75kDa- and p55kDa-IL-2R-gene expression by IL-5 and IL-4, and reinforce our notion that increased expression of high affinity IL-2R induced by IL-5 is responsible for the IL-2 competent state, and decreased expression of p55kDa-IL-2R by IL-4 is responsible for IL-2 unresponsive state.
白细胞介素-5(IL-5)通过增加高亲和力白细胞介素-2受体(IL-2R)的数量,使BCL1-CL-3(CL-3)细胞对IL-2产生反应,而IL-4则抑制IL-5的这种作用,使CL-3细胞对IL-2产生反应。在此,我们发现p75kDa-IL-2R和p55kDa-IL-2R的基因受到IL-4和IL-5的差异调节。未受刺激的CL-3细胞组成性地表达p75kDa-IL-2R和p55kDa-IL-2R的mRNA。IL-5刺激主要增强p75kDa-IL-2R mRNA的表达(4至8倍),尽管适度增加p55kDa-IL-2R mRNA的表达。动力学研究显示,p75kDa-IL-2R mRNA表达在12小时时达到最大增加,此后下降,证实了我们之前关于IL-5刺激后高亲和力IL-2R表达的动力学研究。相比之下,无论CL-3细胞是单独用IL-4刺激还是与IL-5和IL-2一起刺激,IL-4刺激都会适度增加p75kDa-IL-2R mRNA的表达,而显著降低p55kDa-IL-2R mRNA的表达。此外,在含有IL-5和IL-2的培养物中加入IL-4会导致J链mRNA水平显著降低,否则J链mRNA会因IL-5和IL-2的刺激而显著诱导。这些结果清楚地说明了IL-5和IL-4对p75kDa-和p55kDa-IL-2R基因表达的差异调节,并强化了我们的观点,即IL-5诱导的高亲和力IL-2R表达增加导致了IL-2反应性状态,而IL-4导致的p55kDa-IL-2R表达降低导致了IL-2无反应性状态。