血管紧张素Ⅱ通过上调白细胞介素-8受体表达增加单核细胞黏附

Angiotensin Ⅱ Increasing the Monocyte Adhesion Via Up-regulating IL-8 Receptor CXCR2 Expression

目的:探讨血管紧张素II(Ang II)对单核细胞黏附的影响及机制研究。方法:Ang II(10-6 M)培养人单核细胞株4 h或24 h,并加入氯沙坦(1,3,10μM)或抗氧化剂吡咯烷二硫代氨基甲酸盐(PDTC,10μM),检测单核细胞内活性氧(ROS)水平、单核内皮细胞黏附、上清液中白细胞介素-8(IL-8)、肿瘤坏死因子α(TNF-α)水平、单核细胞的白细胞介素-8受体(CXCR2)mRNA表达以及核转录因子κB(NF-κB)和活化蛋白(AP-1)的活性。结果:Ang II(10-6M)孵育单核细胞后显著增加细胞内ROS水平、上清液中白细胞介素-8和肿瘤坏死因子α水平,单核细胞内核转录因子κB和AP-1的活性以及上调CXCR2 mRNA表达,促进单核细胞黏附到内皮细胞。预先给予氯沙坦呈浓度依赖性的抑制Ang II诱导的上述反应,抗氧化剂PDTC同样抑制Ang II诱导的氧化应激和单核细胞黏附。结论:Ang II通过上调CXCR2表达,增加单核细胞黏附,活化单核细胞促进动脉粥样硬化的发生,这一过程涉及ROS-NF-κB/AP-1通路。

Objective： To explore the effect of angiotensin Ⅱ （Ang Ⅱ） increasing the monocyte adhesion with the possible molecular mechanism. Methods： The experimental human monocytoid cells （THP-1） were cultured in 4 groups, each group contained 1×10^6 cells. ① Blank control group, the cells were cultured for 4h or 24 h. ② Ang II treated group, the cells were cultured with Ang II （10-6 M） for 4h or 24 h. ③ Losartan treated group, the cells were cultured with losartan （1, 3, 10）μM for 1 hour and followed-by Ang II （10.6 M） for 4h or 24 h. ④ PDTC group, cells were cultured with the anti oxidative agent PDTC 10 μM for 1.5 h and followed by Ang Ⅱ（10^-6 M） for 4h or 24 h. The intracellular reactive oxygen species （ROS）, the levels of interleukin-8 （IL-8）, tumor necrosis factor （TNF-α in the medium and the adhesion of monocyte to endothelial cells were examined. The expression of CXCR2 mRNA, nuclear factor kappaB （NF-κB） activity and activated protein （AP-1） were determined and compared among different groups. Results： Compared with Blank control group, the Ang II treated group had significantly elevated intracellular ROS, IL-8 and TNF-α, more monocyte adhesion to endothelial cells, higher expression of CXCR2 mRNA, increased activity of NF-κB and AP-1. The above Ang Ⅱ induced up-regulations were inhibited by losartan in a dose-dependent manner. PDTC may also inhibit the Ang Ⅱ induced oxidative stress and monocyte adhesion. Conclusion： Ang Ⅱ activates monocyte for developing atherosclerosis via up-regulating IL-8 receptor CXCR2expression, which might be involved in ROS-NF-κB/AP-1 pathway.