Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Biochem Biophys Res Commun. 2010 Feb 5;392(2):178-82. doi: 10.1016/j.bbrc.2010.01.009. Epub 2010 Jan 7.
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.
血管生成素-1（Ang1）是内皮细胞特异性酪氨酸激酶受体 Tie2 的配体，已被证明在胚胎血管发育中发挥重要作用。关于 Ang1 的抗炎作用已有很多研究，其中大多数都集中在内皮细胞上。在本研究中，我们探讨了 Ang1-Tie2 信号在脂多糖（LPS）刺激下巨噬细胞激活中的作用。我们发现 Tie2 受体在巨噬细胞上表达，Ang1 可以抑制 LPS 诱导的巨噬细胞激活，这表现在细胞迁移和 TNF-α产生方面，具体是通过 Tie2 受体。我们进一步研究了机制，发现 Ang1-Tie2 可以阻断 LPS 诱导的 NF-κB 激活，该激活对于 LPS 处理诱导的巨噬细胞激活是必需的。因此，我们首次描述了 Ang1-Tie2 信号在免疫刺激下的巨噬细胞激活中的作用及其可能的机制。
