Synergistic effects of IL-4 and IL-18 on IL-12-dependent IFN-gamma production by dendritic cells.
Synergistic effects of IL-4 and IL-18 on IL-12-dependent IFN-gamma production by dendritic cells.
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发表时间：
2000
影响因子：
4.4
通讯作者：
T. Fukao;S. Matsuda;S. Koyasu
中科院分区：
文献类型：
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作者：
T. Fukao;S. Matsuda;S. Koyasu
小鼠脾树突状细胞（DC）响应于IL-12产生IFN-γ。在本研究中，我们分析了Th 1和Th 2细胞因子对DC产生IFN-γ的影响。由DC和巨噬细胞产生的IL-18以自分泌方式起作用，并增强DC的IL-12诱导的IFN-γ产生，如在T和NK细胞中也观察到的。令人惊讶的是，IL-4，一种Th 2细胞因子，也与IL-12协同作用于DC产生IFN-γ。此外，当DC通过CD 40或MHC II类刺激时，IL-4显著增强IFN-γ的产生。这些结果表明，Th 1和Th 2细胞因子作用于DC在T细胞-DC相互作用时Ag呈递。p38丝裂原活化蛋白激酶在成熟DC中被组成性激活，并且是DC产生IFN-γ所需的。IL-18而不是IL-4或IL-12进一步激活p38促分裂原活化蛋白激酶活性，表明IL-4和IL-18通过不同的细胞内信号转导途径增强DC中IFN-γ的产生。
Mouse splenic dendritic cells (DCs) produce IFN-gamma in response to IL-12. In the present study, we analyzed effects of Th1 and Th2 cytokines on IFN-gamma production by DCs. IL-18 produced by DCs and macrophages acts in an autocrine manner and augments IL-12-induced IFN-gamma production by DCs as also observed in T and NK cells. Surprisingly, IL-4, a Th2 cytokine, also acts synergistically with IL-12 on IFN-gamma production by DCs. In addition, IL-4 markedly enhances IFN-gamma production when DCs are stimulated through CD40 or MHC class II. These results indicate that both Th1 and Th2 cytokines act on DCs during T cell-DC interaction upon Ag presentation. p38 mitogen-activated protein kinase is constitutively activated in mature DCs and is required for IFN-gamma production by DCs. IL-18 but not IL-4 or IL-12 further activates the p38 mitogen-activated protein kinase activity, suggesting that IL-4 and IL-18 enhance IFN-gamma production through distinct intracellular signal transduction pathways in DCs.