Divergence of bacterial lipopolysaccharide pro-apoptotic signaling downstream of IRAK-1

被引:55
作者
Bannerman, DD
Tupper, JC
Erwert, RD
Winn, RK
Harlan, JM
机构
[1] Univ Washington, Sch Med, Div Hematol, Dept Surg, Seattle, WA 98104 USA
[2] Univ Washington, Sch Med, Dept Med, Seattle, WA 98104 USA
[3] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA
关键词
D O I
10.1074/jbc.M111249200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The vascular endothelium is a key target of circulating bacterial lipopolysaccharide (LPS). LPS elicits a wide array of endothelial responses, including the up-regulation of cytokines, adhesion molecules, and tissue factor, many of which are dependent on NF-kappaB activation. In addition, LPS has been demonstrated to induce endothelial apoptosis both in vitro and in vivo. Although the mechanism by which LPS activates NF-kappaB has been well elucidated, the signaling pathway(s) involved in LPS-induced apoptosis remains unknown. Using a variety of dominant negative constructs, we have identified a role for MyD88 and interleukin-1 receptor-associated kinase-1 (IRAK-1) in mediating LPS pro-apoptotic signaling in human endothelial cells. We also demonstrate that LPS-induced endothelial NF-kappaB activation and apoptosis occur independent of one another. Together, these data suggest that the proximal signaling molecules involved in LPS-induced NF-kappaB activation have a requisite involvement in LPS-induced apoptosis and that the pathways leading to NF-kappaB activation and apoptosis diverge downstream of IRAK-1.
引用
收藏
页码:8048 / 8053
页数:6
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