The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.

The anti-inflammatory cytokine interleukin 19 is expressed by and angiogenic for human endothelial cells.
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DOI:
10.1161/atvbaha.110.214916
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发表时间:
2011-01
期刊:
Arteriosclerosis, thrombosis, and vascular biology
影响因子:
--
通讯作者:
Autieri MV
Autieri MV
中科院分区:
其他
文献类型:
--
作者:
Jain S;Gabunia K;Kelemen SE;Panetti TS;Autieri MV

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抗炎细胞因子在血管内皮细胞(EC)激活和血管生成过程中的表达和作用尚不清楚。本研究旨在探讨新近发现的Th2型抗炎细胞因子白细胞介素19(IL-19)在EC病理生理机制中的表达及功能。我们用免疫组织化学和免疫印迹法证明IL-19在炎症的人冠状动脉内皮细胞中表达,但在正常人冠状动脉内皮细胞中不表达,并能在培养的人血管内皮细胞中被血清和碱性成纤维细胞生长因子诱导。IL-19具有促有丝分裂、趋化和促进细胞内皮细胞扩散的作用。IL-19激活信号蛋白STAT3、P44/42和rac1。在功能性体外研究中,IL-19促进培养的EC形成索状结构,并在小鼠主动脉环实验中促进微血管萌发。IL-19可在体内诱导Matrigel栓形成管状结构。这些结果首次报道了抗炎IL-19在EC中的表达,并首次表明IL-19对EC具有促有丝分裂和趋化作用,并能诱导EC的血管生成潜能。
The expression and effects of anti-inflammatory interleukins on endothelial cell (EC) activation and development of angiogenesis is uncharacterized. The purpose of this study is to characterize the expression and function of Interleukin-19 (IL-19), a recently described Th2 anti-inflammatory interleukin on EC pathophysiology. We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal human coronary endothelium, and can be induced in cultured human EC by serum and bFGF. IL-19 is mitogenic, chemotactic, and promotes cell EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cord-like structure formation of cultured EC and also enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in matrigel plugs in vivo. These data are the first to report expression of the anti-inflammatory interleukin IL-19 in EC, and the first to indicate that IL-19 is mitogenic and chemotactic for EC, and can induce the angiogenic potential of EC.