Hydrogen peroxide stimulates macrophage vascular endothelial growth factor release
Hydrogen peroxide stimulates macrophage vascular endothelial growth factor release
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DOI：
10.1152/ajpheart.2001.280.5.h2357
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发表时间：
2001-05-01
影响因子：
4.8
通讯作者：
Hussain, MZ
中科院分区：
文献类型：
--
作者：
Cho, M;Hunt, TK;Hussain, MZ
中性粒细胞在创伤后不久聚集在伤口部位并释放杀菌活性氧（ROS）和H2 O2以杀死细菌并防止感染。巨噬细胞响应环境刺激到达伤口，吞噬外来颗粒，并释放血管内皮生长因子（VEGF），一种对伤口愈合至关重要的血管生成因子。由于氧化剂在炎症早期释放，并已被发现调节转录因子，我们研究了H2 O2在VEGF刺激中的可能作用。人U937巨噬细胞暴露于H2 O2，并允许在无H2 O2的培养基中迅速恢复，显示VEGF mRNA的增加。H2 O2介导的mRNA增加是剂量依赖性的，被过氧化氢酶阻断，并与条件培养基中VEGF升高相关。在原代大鼠腹腔巨噬细胞和RAW 264.7鼠巨噬细胞系中也发现VEGF增加。放线菌素D的转录抑制显示mRNA半衰期没有显着差异。用1.6-kb VEGF启动子-荧光素酶构建体（Shima DT，Kuroki M，多伊奇U，Ng YS，Adamis AP，和D 'Amore PA. J Biol Chem 271：3877-3883，1996）显示VEGF基因启动子活性的九倍刺激。我们的结论是，过氧化氢增加巨噬细胞VEGF通过氧化剂诱导的VEGF启动子。这种氧化剂刺激可以由活化的中性粒细胞介导。
Neutrophils gather at the wound site shortly after trauma and release bactericidal reactive oxygen species (ROS) and H2O2 to kill bacteria and prevent infection. Macrophages arrive at the wound in response to environmental stimuli, phagocytose foreign particles, and release vascular endothelial growth factor (VEGF), an angiogenic factor crucial for wound healing. Because oxidants are released early in inflammation and have been found to regulate transcription factors, we investigated a possible role of H2O2 in VEGF stimulation. Human U937 macrophages exposed to H2O2 and allowed to recover in H2O2-free medium rapidly showed an increase in VEGF mRNA. The H2O2-mediated mRNA increase was dose dependent, blocked by catalase, and associated with elevated VEGF in conditioned media. The increase in VEGF was also found in primary rat peritoneal macrophages and the RAW 264.7 murine macrophage cell line. Transcriptional inhibition with actinomycin D revealed no significant difference in mRNA half-life. Transient transfections with a 1.6-kb VEGF promoter-luciferase construct (Shima DT, Kuroki M, Deutsch U, Ng YS, Adamis AP, and D'Amore PA. J Biol Chem 271: 3877-3883, 1996) showed a ninefold stimulation of VEGF gene promoter activity. We concluded that H2O2 increases macrophage VEGF through an oxidant induction of VEGF promoter. This oxidant stimulation can be mediated by activated neutrophils.