Lipoxin A4: Anti-Inflammatory and Anti-Angiogenic Impact on Endothelial Cells

被引:81
作者
Baker, Nicole [1 ]
O'Meara, Sarah J. [1 ]
Scannell, Michael [1 ]
Maderna, Paola [1 ]
Godson, Catherine [1 ]
机构
[1] Univ Coll Dublin, Sch Med & Med Sci, Diabet Res Ctr, Conway Inst, Dublin 4, Ireland
基金
爱尔兰科学基金会;
关键词
VASCULAR-PERMEABILITY FACTOR; GROWTH-FACTOR; APOPTOTIC NEUTROPHILS; LEUKOTRIENE D-4; MESANGIAL CELLS; STABLE ANALOGS; NITRIC-OXIDE; MAP KINASES; CROSS-TALK; INFLAMMATION;
D O I
10.4049/jimmunol.0803175
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Lipoxins (LX) are a class of eicosanoid that possesses a wide spectrum of antiinflammatory and proresolution bioactions. Here we have investigated the impact of the endogenously produced eicosanoid LXA(4) on endothelial cell inflammatory, proliferative, and antigenic responses. Using HUVECs we demonstrate that LXA(4) inhibits vascular endothelial growth factor (VEGF)-stimulated inflammatory responses including IL-6, TNF-alpha, IFN-gamma and IL-8 secretion, as well as endothelial ICAM-1 expression. Interestingly, LXA(4) up-regulated IL-10 production from HUVECs. Consistent with these antiinflammatory and proresolution responses to LXA(4), we demonstrate that LXA(4) inhibited leukotriene D-4 and VEGF-stimulated proliferation and angiogenesis as determined by tube formation of HUVECs. We have explored the underlying molecular mechanisms and demonstrate that LXA(4) pretreatment is associated with the decrease of VEGF-stimulated VEGF receptor 2 (KDR/FLK-1) phosphorylation and downstream signaling events including activation of phospholipase C-gamma, ERK1/2, and Akt. The Journal of Immunology, 2009, 182: 3819-3826.
引用
收藏
页码:3819 / 3826
页数:8
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