TIRAP mediates endotoxin-induced NF-κB activation and apoptosis in endothelial cells
TIRAP mediates endotoxin-induced NF-κB activation and apoptosis in endothelial cells
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DOI：
10.1016/s0006-291x(02)00638-1
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发表时间：
2002-07-05
影响因子：
3.1
通讯作者：
Harlan, JM
中科院分区：
文献类型：
--
作者：
Bannerman, DD;Erwert, RD;Harlan, JM
细菌脂多糖 (LPS) 在血管内皮细胞中引发多种信号传导事件，从而导致激活和/或细胞死亡。 LPS 诱导的内皮细胞激活引发多种血管内皮反应，其中许多反应依赖于 NF-κB 激活。据报道，介导 LPS 诱导的 NF-κB 激活的几种信号分子，包括 Tlr-4、MyD88 和 IRAK-1，也可介导 LPS 促凋亡信号传导。最近，一种新的信号分子 TIRAP 被发现可以介导单核细胞和巨噬细胞中 LPS 诱导的 NF-κB 信号传导。使用 TIRAP 显性失活构建体，我们确定了 TIRAP 在介导 LPS 诱导的人内皮细胞 NF-κB 激活和凋亡中的作用。这些数据将 TIRAP 确定为双重功能信号分子，并表明人内皮细胞中存在不依赖于 MyD88 的 LPS 信号通路。 (C) 2002 年爱思唯尔科学（美国）。版权所有。
Bacterial lipopolysaccharide (LPS) initiates multiple signaling events in vascular endothelial cells that can result in activation and/or cell death. LPS-induced activation of endothelial cells elicits a wide array of vascular endothelial responses, many of which are dependent on NF-kappaB activation. Several of the signaling molecules that mediate LPS-induced NF-kappaB activation, including Tlr-4, MyD88, and IRAK-1, have been similarly reported to mediate LPS pro-apoptotic signaling. Recently, a new signaling molecule, TIRAP, has been identified that mediates LPS-induced NF-kappaB signaling in monocytes and macrophages. Using a TIRAP dominant negative construct, we have identified a role for TIRAP in mediating LPS-induced NF-kappaB activation and apoptosis in human endothelial cells. These data identify TIRAP as a dual functioning signaling molecule and suggest the presence of a MyD88-independent LPS signaling pathway in human endothelial cells. (C) 2002 Elsevier Science (USA). All rights reserved.