title: Angiopoietin-1 elicits pro-inflammatory responses in monocytes and differentiating macrophages.
abstract: The angiopoietin/Tie2 system is an important regulator of angiogenesis and inflammation. In addition to its functions in endothelial cells, Tie2 expression on non-endothelial cells allows for angiopoietin ligands to stimulate the cells. Although Ang1 is a strong Tie2 receptor agonist, little is known regarding the effect of Ang1 on non-endothelial cells, such as monocytes and macrophages. In this study, we found that Ang1 functionally binds to and stimulates monocytes via p38 and Erk1/2 phosphorylation. Ang1-mediated monocyte stimulation is associated with proinflammatory cytokine TNF-α expression. We also determined that Ang1 switched macrophage differentiation toward a pro-inflammatory phenotype, even in the presence of an anti-inflammatory mediator. These findings suggest that Ang1 plays a role in stimulating pro-inflammatory responses and could provide a new strategy by which to manage inflammatory responses.
authors.affiliation: Department of Microbiology and Immunology and Institute of Endemic Disease, The Catholic University of Korea, Seoul 137-701, Korea.
authors.forename: Seung Hyeok
authors.initials: SH
authors.lastname: Seok
authors.forename: Jong-Ik
authors.initials: JI
authors.lastname: Heo
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Hwang
authors.forename: Yi-Rang
authors.initials: YR
authors.lastname: Na
authors.forename: Jang-Hyuk
authors.initials: JH
authors.lastname: Yun
authors.forename: Eun Hui
authors.initials: EH
authors.lastname: Lee
authors.forename: Jong-Wan
authors.initials: JW
authors.lastname: Park
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D018919:Neovascularization, Physiologic; D010766:Phosphorylation; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D042683:Angiopoietin-1; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D042787:Receptor, TIE-2; D048051:p38 Mitogen-Activated Protein Kinases