Osmotic stress blocks NF-kappaB-dependent inflammatory responses by inhibiting ubiquitination of IkappaB.
Osmotic stress blocks NF-kappaB-dependent inflammatory responses by inhibiting ubiquitination of IkappaB.
复制标题
渗透压通过抑制 IkappaB 泛素化来阻断 NF-kappaB 依赖性炎症反应。
DOI：
10.1016/j.febslet.2007.11.002
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发表时间：
2007
期刊：
影响因子：
3.5
通讯作者：
Ninomiya-Tsuji,Jun
中科院分区：
文献类型：
--
作者：
HuangFu,Wei-Chun;Matsumoto,Kunihiro;Ninomiya-Tsuji,Jun
在临床研究中已经描述了高渗条件对免疫应答的抑制作用;然而，这种现象背后的分子机制尚未确定。在这里，我们研究渗透压介导的NF-κB通路的修饰，NF-κ B通路是炎症中的一个中心信号通路。我们意外地发现，渗透胁迫可以激活IκBα激酶，但不能激活NF-κB。渗透应激诱导的磷酸化IκBα未被泛素化，渗透应激抑制白细胞介素1诱导的IκBα的泛素化，并最终阻断细胞因子/趋化因子的表达。因此，阻断IκBα泛素化可能是高渗条件下抑制炎症的主要机制。
The inhibitory effects of hypertonic conditions on immune responses have been described in clinical studies; however, the molecular mechanism underlying this phenomenon has yet to be defined. Here we investigate osmotic stress-mediated modification of the NF-κB pathway, a central signaling pathway in inflammation. We unexpectedly found that osmotic stress could activate IκBα kinase but did not activate NF-κB. Osmotic stress-induced phosphorylated IκBα was not ubiquitinated, and osmotic stress inhibited interleukin 1-induced ubiquitination of IκBα and ultimately blocked expression of cytokine/chemokines. Thus, blockage of IκBα ubiquitination is likely to be a major mechanism for inhibition of inflammation by hypertonic conditions.