Interleukin-6 promotes the production of interleukin-4 and interleukin-5 by interleukin-2-dependent and -independent mechanisms in freshly isolated human T cells
Interleukin-6 promotes the production of interleukin-4 and interleukin-5 by interleukin-2-dependent and -independent mechanisms in freshly isolated human T cells
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DOI：
10.1046/j.1365-2567.2002.01501.x
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发表时间：
2002-11-01
期刊：
影响因子：
6.4
通讯作者：
Kauffman, HF
中科院分区：
文献类型：
--
作者：
Heijink, IH;Vellenga, E;Kauffman, HF
辅助性T细胞2(Th2)细胞因子[IL-4和IL-5]在变态反应性免疫反应的发生发展中起核心作用。过敏原刺激后，特应性和哮喘患者Th2细胞因子的表达迅速上调。IL-6是一种多功能细胞因子，可直接诱导Th2免疫应答，由多种组织细胞分泌。本研究表明，在新分离的α-CD3/α-CD28刺激的T细胞中，IL-6在短时间(5分钟)预孵育后诱导IL-4和IL-5的上调。经过较长时间的IL-6预孵育(12小时和24小时)后，对IL-4产生的启动作用逐渐消失，而对IL-5的作用变得更加明显。相反，发现对Th1细胞因子干扰素-伽马的产生有轻微但显著的抑制作用。另外的实验表明，IL-6对IL-5产生的长期启动作用依赖于IL-2信号。IL-6对IL-5分泌的短期影响不是这样的，其中涉及p38丝裂原激活蛋白激酶依赖的激活蛋白-1DNA结合活性的诱导，而不是信号转导和转录激活因子3的磷酸化。综上所述，这些数据表明IL-6对Th2细胞因子产生的短期和长期启动效应是由不同的机制调节的。
T helper 2 (Th2) cytokines [interleukin (IL)-4 and IL-5] play a central role in the development of allergic immune responses. After allergen provocation, the expression of Th2 cytokines is rapidly up-regulated in atopy and asthma. IL-6 is a multifunctional cytokine that is able to direct Th2 immune responses and is secreted by multiple tissue cell types. This study shows that IL-6 induces up-regulation of IL-4 and IL-5 after short (5 min) preincubation periods in freshly isolated, alpha-CD3/ alpha-CD28-stimulated T cells. After longer preincubation periods with IL-6 (12 and 24 hr), the priming effect on IL-4 production gradually disappears, whereas the effect on IL-5 becomes more pronounced. In contrast, a small but significant inhibitory effect is found on the production of the Th1 cytokine interferon-gamma. Additional experiments indicate that the long-term priming effect of IL-6 on IL-5 production is dependent on IL-2 signalling. This is not the case for the short-term IL-6 effect on IL-5 secretion, where the p38 mitogen-activated protein kinase-dependent induction of activator protein-1 DNA-binding activity is involved, independent of signal transducer and activator of transcription 3 phosphorylation. In summary, these data demonstrate that the short-term and long-term priming effects of IL-6 on Th2 cytokine production are regulated by different mechanisms.