Requirement for type 2 NO synthase for IL-12 signaling in innate immunity
Requirement for type 2 NO synthase for IL-12 signaling in innate immunity
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DOI：
10.1126/science.284.5416.951
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发表时间：
1999-05-07
期刊：
影响因子：
56.9
通讯作者：
Bogdan, C
中科院分区：
文献类型：
--
作者：
Diefenbach, A;Schindler, H;Bogdan, C
白细胞介素-12（IL-12）和2型一氧化氮合酶（NOS 2）对于防御细菌和寄生虫病原体至关重要，但它们在先天免疫中的关系尚不清楚。在没有NOS 2活性的情况下，IL-12不能防止利什曼原虫的传播，不能刺激自然杀伤（NK）细胞的细胞毒性或干扰素-γ（IFN-γ）的释放，并且不能激活NK细胞中的Tyk 2激酶和酪氨酸磷酸化Stat 4（IL-12的中心信号转导子）。IFN-α/β激活NK细胞中的Tyk 2也需要NOS 2。因此，NOS 2衍生的NO是先天免疫中细胞因子信号传导和功能的先决条件。
Interleukin-12 (IL-12) and type 2 NO synthase (NOS2) are crucial for defense against bacterial and parasitic pathogens, but their relationship in innate immunity is unknown. in the absence of NOS2 activity, IL-12 was unable to prevent spreading of Leishmania parasites, did not stimulate natural killer (NK) cells for cytotoxicity or interferon-gamma (IFN-gamma) release, and failed to activate Tyk2 kinase and to tyrosine phosphorylate Stat4 (the central signal transducer of IL-12) in NK cells. Activation of Tyk2 in NK cells by IFN-alpha/beta also required NOS2. Thus, NOS2-derived NO is a prerequisite for cytokine signaling and function in innate immunity.