Human β-Defensin 3 Reduces TNF-α-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells.
Human β-Defensin 3 Reduces TNF-α-Induced Inflammation and Monocyte Adhesion in Human Umbilical Vein Endothelial Cells.
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人 β-防御素 3 减少 TNF-α 诱导的人脐静脉内皮细胞炎症和单核细胞粘附
DOI：
10.1155/2017/8529542
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发表时间：
2017
影响因子：
4.6
通讯作者：
Yan F
中科院分区：
文献类型：
--
作者：
Bian T;Li H;Zhou Q;Ni C;Zhang Y;Yan F
本研究旨在探讨人β-防御素3（hBD 3）在肿瘤坏死因子-α（TNF-α）诱导的人脐静脉内皮细胞（HUVECs）动脉粥样硬化形成中的作用。观察hBD 3对TNF-α诱导的内皮损伤和炎症反应的影响。我们的数据显示，首先，hBD 3以剂量依赖性方式减少HUVECs中白细胞介素-6（IL-6）、IL-8、单核细胞趋化蛋白-1（MCP-1）和巨噬细胞移动抑制因子（MIF）的产生。此外，hBD 3显着阻止细胞内活性氧（ROS）的生产HUVEC。第二，western blot分析表明hBD 3剂量依赖性地抑制TNF-α诱导的HUVECs中细胞内粘附分子-1（ICAM-1）和血管细胞粘附分子-1（VCAM-1）的蛋白水平。结果表明，hBD 3抑制单核细胞与TNF-α处理的内皮细胞的粘附。此外，hBD 3抑制TNF-α诱导的HUVECs中的F-actin重组。第三，hBD 3在30 min内通过降低IKK-α/β、IκB和p65亚基的磷酸化水平，显著抑制NF-κB的活化。此外，hBD 3还抑制HUVEC中有丝分裂原活化蛋白激酶（MAPK）途径中p38和c-Jun N末端蛋白激酶（JNK）的磷酸化。结论：hBD 3通过抑制NF-κB和MAPK信号通路在TNF-α诱导的内皮细胞中发挥抗炎和抗氧化作用。
The aim of this study was to investigate the role of human β-defensin 3 (hBD3) in the initiation stage of atherosclerosis with human umbilical vein endothelial cells (HUVECs) triggered by tumor necrosis factor- (TNF-) α. The effects of hBD3 on TNF-α-induced endothelial injury and inflammatory response were evaluated. Our data revealed that first, hBD3 reduced the production of interleukin-6 (IL-6), IL-8, monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor (MIF) in HUVECs in a dose-dependent manner. In addition, hBD3 significantly prevented intracellular reactive oxygen species (ROS) production by HUVECs. Second, western blot analysis demonstrated that hBD3 dose-dependently suppressed the protein levels of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-induced HUVECs. As a result, hBD3 inhibited monocyte adhesion to TNF-α-treated endothelial cells. Additionally, hBD3 suppressed TNF-α-induced F-actin reorganization in HUVECs. Third, hBD3 markedly inhibited NF-κB activation by decreasing the phosphorylation of IKK-α/β, IκB, and p65 subunit within 30 min. Moreover, the phosphorylation of p38 and c-Jun N-terminal protein kinase (JNK) in the mitogen-activated protein kinase (MAPK) pathway were also inhibited by hBD3 in HUVECs. In conclusion, hBD3 exerts anti-inflammatory and antioxidative effects in endothelial cells in response to TNF-α by inhibiting NF-κB and MAPK signaling.