OxLDL inhibits LPS-induced IFNβ expression by Pellino3- and IRAK1/4-dependent modification of TANK
In: Cellular Signalling, Jg. 24 (2012-06-01), Heft 6, S. 1141-1149
Online
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Zugriff:
Abstract: In atherosclerosis macrophages contribute to disease progression. After infiltrating atherosclerotic lesions they accumulate oxLDL (oxidized low density lipoproteins) and differentiate into foam cells. During this process inhibition of TLR4 (Toll-like receptor 4)-dependent IFNβ expression occurs. To understand molecular mechanisms how oxLDL inhibits LPS-induced IFNβ expression in macrophage-derived foam cells, we analyzed the impact of oxLDL on signaling pathways upstream of IFNβ expression. We identified mono-ubiquitination of TANK (TRAF family member-associated NFκB activator), a scaffold protein of the TRIF (TIR-domain-containing adapter-inducing IFNβ)-dependent TLR4-signaling cascade. Modified TANK inhibits recruitment of TBK1 (TANK-binding kinase 1) to TRAF3 (TNF receptor associated factor 3) and the subsequent activation of the transcription factor IRF3 (interferon regulatory factor 3). OxLDL stimulates TANK mono-ubiquitination by subsequent activation of IRAK1/4 (interleukin-1 receptor-associated kinases 1 and 4) and Pellino3 downstream of SR-A1 (scavenger receptor-A1). Our observations highlight the regulatory impact of IRAK1/4 and Pellino3 on the TRIF-dependent TLR4-signaling cascade, which might be of general importance for disease conditions associated with macrophage pathologies such as atherosclerosis. [Copyright &y& Elsevier]
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OxLDL inhibits LPS-induced IFNβ expression by Pellino3- and IRAK1/4-dependent modification of TANK
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Autor/in / Beteiligte Person: | Tzieply, Nico ; Kuhn, Anne-Marie ; Morbitzer, Daniel ; Namgaladze, Dmitry ; Heeg, Annika ; Schaefer, Liliana ; von Knethen, Andreas ; Jensen, Liselotte E. ; Brüne, Bernhard |
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Zeitschrift: | Cellular Signalling, Jg. 24 (2012-06-01), Heft 6, S. 1141-1149 |
Veröffentlichung: | 2012 |
Medientyp: | academicJournal |
ISSN: | 0898-6568 (print) |
DOI: | 10.1016/j.cellsig.2012.01.021 |
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