c-Fos suppresses systemic inflammatory response to endotoxin
c-Fos suppresses systemic inflammatory response to endotoxin
复制标题
DOI：
10.1093/intimm/dxl004
复制
发表时间：
2006-05-01
影响因子：
4.4
通讯作者：
Matsuo, K
中科院分区：
文献类型：
--
作者：
Ray, N;Kuwahara, M;Matsuo, K
我们使用缺乏c-Fos的小鼠（Fos（-/-）小鼠）探索了转录因子c-Fos在脂多糖（LPS）诱导的细胞因子应答中的作用。与野生型对照组相比，Fos（-/-）巨噬细胞和小鼠的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-12 p40的产生显著增加，但抗炎细胞因子IL-10的产生减少。带移分析显示，LPS诱导的NF-κ B与TNF-α启动子功能位点的结合活性在Fos（-/-）中显著高于野生型巨噬细胞。使用遥测技术，我们在LPS注射后监测体温和心率，发现Fos（-/-）小鼠比野生型小鼠经历更严重的体温过低和心动过缓。Fos（-/-）小鼠的这种休克反应可通过中和TNF-α而显著逆转。这些数据揭示了c-Fos作为通过抑制NF-κ B活性起作用的抗炎转录因子的新的体内作用。
We explored the role of the transcription factor c-Fos in lipopolysaccharide (LPS)-induced cytokine response using mice lacking c-Fos (Fos(-/-) mice). Compared with wild-type controls, Fos(-/-) macrophages and mice showed significantly enhanced production of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-12 p40, but reduced production of the anti-inflammatory cytokine IL-10. Bandshift analysis revealed that LPS-induced NF-kappa B binding activity to a functional site in the TNF-alpha promoter was significantly higher in Fos(-/-) than in wild-type macrophages. Using telemetry, we monitored body temperature and heart rate after LPS injection and found that Fos(-/-) mice undergo more severe hypothermia and bradycardia than wild-type mice. Such shock responses in Fos(-/-) mice were significantly reversed by neutralizing TNF-alpha. These data reveal a novel in vivo role for c-Fos as an anti-inflammatory transcription factor acting through suppression of NF-kappa B activity.