Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung
Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung
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DOI：
10.1038/nm1105
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发表时间：
2004-10-01
期刊：
影响因子：
82.9
通讯作者：
Elias, JA
中科院分区：
文献类型：
--
作者：
Lee, CG;Link, H;Elias, JA
在哮喘患者中存在VEGF（血管内皮生长因子）水平升高，但VEGF在正常和哮喘肺中的作用尚未确定。我们建立了肺靶向VEGF（165）转基因小鼠，并评估了VEGF在T辅助细胞2型（T（H）2）介导的炎症中的作用。在这些小鼠中，VEGF通过IL-13依赖性和非依赖性途径诱导哮喘样表型，伴有炎症、实质和血管重塑、水肿、粘液化生、肌细胞增生和气道高反应性。VEGF还增强了呼吸道抗原致敏和T（H）2炎症，并增加了活化的DC 2树突状细胞的数量。在抗原诱导的炎症中，VEGF由上皮细胞产生，并且优先由T（H）2细胞而不是T（H）1细胞产生。在这种情况下，它在T（H）2炎症、细胞因子产生和生理失调中起关键作用。因此，VEGF是血管和血管外重塑和炎症的介质，其增强抗原致敏，并且在适应性T（H）2炎症中至关重要。调节VEGF可能对哮喘和其他T（H）2紊乱有治疗作用。
Exaggerated levels of VEGF (vascular endothelial growth factor) are present in persons with asthma, but the role(s) of VEGF in normal and asthmatic lungs has not been defined. We generated lung-targeted VEGF(165) transgenic mice and evaluated the role of VEGF in T-helper type 2 cell (T(H)2)-mediated inflammation. In these mice, VEGF induced, through IL-13-dependent and -independent pathways, an asthma-like phenotype with inflammation, parenchymal and vascular remodeling, edema, mucus metaplasia, myocyte hyperplasia and airway hyper-responsiveness. VEGF also enhanced respiratory antigen sensitization and T(H)2 inflammation and increased the number of activated DC2 dendritic cells. In antigen-induced inflammation, VEGF was produced by epithelial cells and preferentially by T(H)2 versus T(H)1 cells. In this setting, it had a critical role in T(H)2 inflammation, cytokine production and physiologic dysregulation. Thus, VEGF is a mediator of vascular and extravascular remodeling and inflammation that enhances antigen sensitization and is crucial in adaptive T(H)2 inflammation. VEGF regulation may be therapeutic in asthma and other T(H)2 disorders.