The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice.
The TRIF-dependent signaling pathway is not required for acute cerebral ischemia/reperfusion injury in mice.
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DOI：
10.1016/j.bbrc.2009.10.027
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发表时间：
2009-12-18
影响因子：
3.1
通讯作者：
Stein, Donald G.
中科院分区：
文献类型：
--
作者：
Hua, Fang;Wang, Jun;Sayeed, Iqbal;Ishrat, Tauheed;Atif, Fahim;Stein, Donald G.
含有TIR结构域的衔接蛋白（TRIF）是Toll样受体（TLR）信号通路中的衔接蛋白。TRIF的活化导致干扰素调节因子3（IRF 3）和核因子κ B（NF-κB）的活化。尽管研究表明TLR参与脑缺血/再灌注（I/R）损伤和预处理提供的抗缺血的神经保护作用，但对TRIF在脑I/R后的病理过程中的作用知之甚少。本研究探讨TRIF在急性脑I/R损伤中的作用。在短暂性大脑中动脉闭塞诱导的小鼠脑I/R模型中，我们使用ELISA和Western印迹检测了缺血脑组织中NFκB和IRF-3信号的活化。在脑I/R后24小时评估神经功能和脑梗死面积。在缺血性脑中，NF-κB活性和κ B抑制剂（IκBα）的磷酸化增加，但在野生型（WT）小鼠脑I/R后，IRF 3、κB激酶复合物-ε抑制剂（IKKε）和TANK结合激酶1（TBK 1）未被激活。有趣的是，TRIF缺陷并不抑制脑I/R诱导的NF-κB活性或p-IκBα。此外，尽管脑I/R在WT小鼠中诱导神经和功能障碍以及脑梗死，但与WT小鼠相比，TRIF敲除小鼠的缺陷没有改善，脑梗死面积没有减少。我们的结果表明，急性脑I/R后NF-κB信号传导的激活和脑损伤并不需要TRIF依赖性信号通路。
TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of Interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-κB). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF’ role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NFκB and IRF-3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 hours after cerebral I/R. NF-κB activity and phosphorylation of the inhibitor of kappa B (IκBα) increased in ischemic brains, but IRF3, inhibitor of κB kinase complex-ε (IKKε), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-κB activity or p-IκBα induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-κB signaling and brain injury after acute cerebral I/R.
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影响因子：
8.3
作者：
GARCIA, JH;WAGNER, S;HU, XJ
通讯作者：
HU, XJ
DOI：
10.1016/j.jtcvs.2006.12.056
发表时间：
2007-06-01
影响因子：
6
作者：
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通讯作者：
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
5.3
作者：
Kaushal, Vikas;Schlichter, Lyanne C.
通讯作者：
Schlichter, Lyanne C.
影响因子：
12.3
作者：
De Simoni, MG;Milia, P;Gallai, V
通讯作者：
Gallai, V