TIRAP mediates endotoxin-induced NF-kappaB activation and apoptosis in endothelial cells |
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Authors: | Bannerman Douglas D Erwert Ryan D Winn Robert K Harlan John M |
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Institution: | Department of Surgery, University of Washington School of Medicine, Seattle, WA 98104, USA. dbannerm@u.washington.edu |
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Abstract: | 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. |
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Keywords: | Endothelium Endotoxin Apoptosis NF-κB Toll-like receptor-4 |
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