TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses
TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses
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DOI：
10.1016/s1074-7613(00)80113-2
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发表时间：
1999-09-01
期刊：
影响因子：
32.4
通讯作者：
Yeh, WC
中科院分区：
文献类型：
--
作者：
Nguyen, LT;Duncan, GS;Yeh, WC
肿瘤坏死因子受体相关因子2(TRAF2)可与肿瘤坏死因子受体家族的多种成员相互作用。在此之前，我们曾报道TRAF2基因缺陷的小鼠会过早死亡，并且血清中的肿瘤坏死因子水平升高。在这项研究中，我们证明了缺乏TRAF2的巨噬细胞在对肿瘤坏死因子刺激的反应中产生了更多的一氧化氮(NO)和肿瘤坏死因子。此外，我们可以通过消除肿瘤坏死因子或肿瘤坏死因子受体1来提高TRAF2缺陷小鼠的存活率。利用这些双基因敲除小鼠，我们发现在没有TRAF2的情况下，T辅助抗体反应、CD40介导的增殖和核因子-kappaB的激活是有缺陷的。这些数据显示了TRAF2的两个重要作用，一个是作为某些TNFR1信号的负向调节因子，另一个是作为CD40信号的正向调节因子。
Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) can interact with various members of the TNF receptor family. Previously, we reported that TRAF2-deficient mice die prematurely and have elevated serum TNF levels. In this study, we demonstrate that TRAF2-deficient macrophages produce increased amounts of nitric oxide (NO) and TNF in response to TNF stimulation. Furthermore, we could enhance the survival of TRAF2-deficient mice by eliminating either TNF or TNFR1. Using these double-knockout mice, we show that in the absence of TRAF2, the T helper-dependent antibody response, CD40-mediated proliferation, and NF-kappa B activation are defective. These data demonstrate two important roles of TRAF2, one as a negative regulator of certain TNFR1 signals and the other as a positive mediator of CD40 signaling.