Ets2 suppresses inflammatory cytokines through MAPK/NF-κB signaling and directly binds to the IL-6 promoter in macrophages
Ets2 suppresses inflammatory cytokines through MAPK/NF-κB signaling and directly binds to the IL-6 promoter in macrophages
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Ets2 通过 MAPK/NF-κB 信号传导抑制炎症细胞因子，并直接与巨噬细胞中的 IL-6 启动子结合
DOI：
10.18632/aging.102480
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发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Ma, Xianwei;Jiang, Zhengyu;Zhang, Yan
toll样受体（TLR）介导的信号传导的适当激活和促炎细胞因子的产生对先天免疫的启动至关重要，而维持炎症稳态的具体机制大多尚不清楚。在这里，我们发现在LPS和VSV刺激后，Ets2上调。Ets2敲除或敲除导致巨噬细胞中IL-6、TNF-α和IFN-β的产生增加。与此一致的是，缺乏ets2的小鼠炎症细胞因子产生加剧，更容易发生clp诱导的败血症。在机制上，Ets2抑制LPS和vsv诱导的ERK1/2、JNK、p38和p65的激活。Ets2还结合IL-6启动子抑制转录。综上所述，本研究结果表明，Ets2通过抑制MAPK/NF-κ b信号传导、直接结合IL-6启动子和抑制转录，在LPS和vsv诱导的炎症中发挥负调控作用。
Proper activation of Toll-like receptor (TLR)-mediated signaling and production of proinflammatory cytokines are critical for the initiation of innate immunity, while the specific mechanism maintaining inflammatory homeostasis remains mostly unknown. Here, we show that Ets2 is upregulated following LPS and VSV stimulation. Ets2 knockdown or knockout leads to increased IL-6, TNF-α, and IFN-β production in macrophages. Consistently, Ets2-deficient mice show exacerbated inflammatory cytokine production and are more susceptible to CLP-induced sepsis. Mechanistically, Ets2 inhibits the LPS- and VSV-induced activation of ERK1/2, JNK, p38, and p65. Ets2 also binds to the promoter of IL-6 to inhibit transcription. Collectively, the results of the present study show the negative regulatory role of Ets2 in LPS- and VSV-induced inflammation through the suppression of MAPK/NF-κB signaling, direct binding to the IL-6 promoter and inhibition of transcription.