Hu Hejing, Wu Jing, Li Qiuling, Asweto Collins, Feng Lin, Yang Xiaozhe, Duan Fengkui, Duan Junchao, Sun Zhiwei
Department of Toxicology and Sanitary Chemistry , School of Public Health , Capital Medical University , Beijing 100069 , P.R. China . Email:
Beijing Key Laboratory of Environmental Toxicology , Capital Medical University , Beijing 100069 , P.R. China.
Toxicol Res (Camb). 2016 Apr 4;5(3):946-953. doi: 10.1039/c5tx00351b. eCollection 2016 May 1.
Exposure to PM2.5 has been strongly linked to endothelial dysfunction. However, the underlying mechanism of PM2.5 on the vascular endothelial function is poorly understood. This study examined the toxic effect and underlying mechanism of PM2.5 on human umbilical vein endothelial cells (HUVECs). Decreased cell viability and increased LDH activity were observed in the PM2.5-treated HUVECs in a dose-dependent manner. The production of ROS, MDA, and the inhibition of SOD activity were also triggered by PM2.5 in HUVECs. In addition, PM2.5 increased the intracellular levels of proinflammatory cytokines (IL-6, TNF-a, IL-1β, IL-8 and CRP), cell adhesion molecules (ICAM-1, VCAM-1) and tissue factor (TF), resulted in endothelial activation. For an in-depth study, the protein levels of IL-6, JAK1 and STAT3 were up-regulated significantly, while the expression of JAK2 and SOCS1 were down-regulated gradually in PM2.5-treated HUVECs in a dose-dependent manner. These results show that PM2.5 triggered endothelial activation upregulation of the IL-6 dependent JAK1/STAT3 signaling pathway. This will provide new insights into the toxic effects and mechanisms of cardiovascular diseases triggered by ambient air pollution.
暴露于细颗粒物（PM2.5）已被证实与内皮功能障碍密切相关。然而，PM2.5影响血管内皮功能的潜在机制仍不清楚。本研究探讨了PM2.5对人脐静脉内皮细胞（HUVECs）的毒性作用及其潜在机制。结果显示，经PM2.5处理的HUVECs细胞活力下降，乳酸脱氢酶（LDH）活性增加，且呈剂量依赖性。PM2.5还可诱导HUVECs产生活性氧（ROS）、丙二醛（MDA），并抑制超氧化物歧化酶（SOD）的活性。此外，PM2.5可增加促炎细胞因子（IL-6、TNF-α、IL-1β、IL-8和C反应蛋白）、细胞黏附分子（ICAM-1、VCAM-1）和组织因子（TF）的细胞内水平，导致内皮细胞活化。进一步深入研究发现，在经PM2.5处理的HUVECs中，IL-6、JAK1和STAT3的蛋白水平显著上调，而JAK2和SOCS1的表达则呈剂量依赖性逐渐下调。这些结果表明，PM2.5可通过上调IL-6依赖的JAK1/STAT3信号通路引发内皮细胞活化。这将为环境空气污染引发心血管疾病的毒性作用和机制提供新的见解。
