Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zirlik, A; Bavendiek, U; Libby, P; MacFarlane, L; Gerdes, N; Jagielska, J; Ernst, S; Aikawa, M; Nakano, H; Tsitsikov, E; Schönbeck, U.
TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells.
ARTERIOSCL THROM VAS. 2007; 27(5): 1101-1107.
Doi: 10.1161/ATVBAHA.107.140566
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- Führende Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 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
- Find related publications in this database (Keywords)
- atherosclerosis
- CD40L
- inflammation
- signaling
- TRAF