Angiopoietin-1/Tie2 signaling pathway inhibits lipopolysaccharide-induced activation of RAW264.7 macrophage cells.
Angiopoietin-1 (Ang1) is a ligand for the endothelial-specific tyrosine kinase receptor Tie2 and has been shown to play an essential role in embryonic vasculature development. There have been many studies about the anti-inflammatory effects of Ang1, most of which focus on endothelium cells. In the present study, we explore the role of Ang1-Tie2 signaling in the activation of macrophages upon lipopolysaccharide (LPS) stimulation. We found that Tie2 receptor is expressed on macrophages and Ang1 could inhibit LPS-induced activation of macrophages, as evidenced by cell migration and TNF-alpha production, specifically through Tie2 receptor. We further investigated the mechanism and found that Ang1-Tie2 could block LPS-induced activation of NF-kappaB which has been shown to be necessary for macrophage activation with LPS treatment. Thus, we described, for the first time, the role of Ang1-Tie2 signaling in macrophage activation and the possible mechanisms in response to immune stimulation.
Gu
Huiping
H
Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Cui
Ming
M
Bai
Yun
Y
Chen
Fengrong
F
Ma
Kangtao
K
Zhou
Chunyan
C
Guo
Lijun
L
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D042683:Angiopoietin-1; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C434062:TNIP2 protein, human; D042787:Receptor, TIE-2