Arteriosclerosis, thrombosis, and vascular biology, 2007-05, Vol.27 (5), p.1101-1107
2007
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Details
- Autor(en) / Beteiligte
- Titel
- TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2007-05, Vol.27 (5), p.1101-1107
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2007
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Several lines of evidence implicate CD40 ligand (CD40L, CD154) as a mediator and marker of atherosclerosis. This study investigated the involvement of tumor necrosis factor receptor-associated factors (TRAFs) in CD40 signaling in endothelial cells (ECs) and their expression in atheromata and cells involved in atherogenesis. CD40L enhanced the basal expression of TRAF-1, -2, -3, and 6, but not TRAF-5 in ECs. TRAFs associated with CD40 on ligation by CD40L. Study of ECs from TRAF-1, -2, and -5-deficient mice demonstrated functional involvement of TRAFs in proinflammatory CD40 signaling. Whereas TRAF-1 deficiency enhanced CD40L-induced IL-6 and MCP-1 expression, TRAF-2 and TRAF-5 deficiency inhibited CD40L-inducible IL-6 but not MCP-1 expression. Gene silencing in human ECs further delineated functions of TRAFs in CD40 signaling. TRAF-3 silencing in ECs showed increased CD40L-induced IL-6, MCP-1, and IL-8 expression, whereas TRAF-6 silencing increased selectively CD40L-induced MCP-1 expression. Enhanced TRAF levels in atherosclerotic lesions further supports involvement of members of this family of signaling molecules in arterial disease. These results implicate endothelial TRAF-1, -2, -3, -5, and -6 in CD40 signaling in atherogenesis, identifying these molecules as potential targets for selective therapeutic intervention.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1079-5642eISSN: 1524-4636DOI: 10.1161/atvbaha.107.140566Titel-ID: cdi_pubmed_primary_17332487
- Format
- –
- Schlagworte
- Animals, Atherosclerosis - etiology, Atherosclerosis - metabolism, Atherosclerosis - pathology, Blotting, Western, CD40 Ligand - immunology, Disease Progression, Endothelial Cells - immunology, Endothelial Cells - metabolism, Endothelial Cells - pathology, Endothelium, Vascular - immunology, Endothelium, Vascular - metabolism, Endothelium, Vascular - pathology, Gene Expression, Humans, Inflammation - metabolism, Inflammation - pathology, Mice, Polymerase Chain Reaction, RNA, Small Interfering - genetics, Saphenous Vein - drug effects, Saphenous Vein - metabolism, Saphenous Vein - pathology, TNF Receptor-Associated Factor 1 - genetics, TNF Receptor-Associated Factor 1 - metabolism, TNF Receptor-Associated Factor 2 - genetics, TNF Receptor-Associated Factor 2 - metabolism, TNF Receptor-Associated Factor 3 - genetics, TNF Receptor-Associated Factor 3 - metabolism, TNF Receptor-Associated Factor 5 - genetics, TNF Receptor-Associated Factor 5 - metabolism, TNF Receptor-Associated Factor 6 - genetics, TNF Receptor-Associated Factor 6 - metabolism