Chen H, Wu L, Chen Y, Wang B
Research Unit of Biomedical Engineering, West China University of Medical Sciences, Chengdu 610041.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2001 Mar;18(1):64-7.
This study sought to demonstrate that IL-8 expression in endothelial cells is regulated by not only chemical factors but also mechanical factors. After pretreating cultured human umbilical vein endothelial cells (HUVECs) with shear stress for different periods of time, we employed RT-PCR to assay IL-8 mRNA expression and immunocytochemical staining to detect NF-kappa B activation in HUVECs. The results showed: 1. IL-8 mRNA expressed little in HUVECs untreated or pretreated with low laiminar shear stress for 0.5 h; IL-8 mRNA expression increased when HUVECs were pretreated with low laminar shear stress for 1 h, and it increased further when HUVECs were pretreated for 2 h; 2. The immunoreactivity of NF-kappa B p65 in the nuclei of HUVECs untreated or pretreated with low laminar shear stress for 0.5 h was negative, while it became weak positive in the nuclei of HUVECs pretreated with shear stress for 1 h and positive in the nuclei of HUVECs pretreated for 2 h. The findings implied that low laminar shear stress was capable of inducing IL-8 gene expression and activating NF-kappa B, which were both time-dependent. The induction of IL-8 gene expression by laminar shear stress is probably due to the activation of NF-kappa B. On these grounds we come to the conclusion that IL-8 expression induced in endothelial cells by low shear stress may play an important role in the genesis and development of both inflammation and arterioatherosclerosis.
本研究旨在证明内皮细胞中白细胞介素-8(IL-8)的表达不仅受化学因素调控,还受机械因素调控。在用不同时长的剪切应力预处理培养的人脐静脉内皮细胞(HUVECs)后,我们采用逆转录聚合酶链反应(RT-PCR)检测HUVECs中IL-8信使核糖核酸(mRNA)的表达,并通过免疫细胞化学染色检测核因子κB(NF-κB)的激活情况。结果显示:1. 未处理的HUVECs或用低切变应力预处理0.5小时的HUVECs中IL-8 mRNA表达较少;当HUVECs用低切变应力预处理1小时时,IL-8 mRNA表达增加,预处理2小时时进一步增加;2. 未处理的HUVECs或用低切变应力预处理0.5小时的HUVECs细胞核中NF-κB p65的免疫反应性为阴性,而在用剪切应力预处理1小时的HUVECs细胞核中变为弱阳性,预处理2小时的HUVECs细胞核中为阳性。这些发现表明低切变应力能够诱导IL-8基因表达并激活NF-κB,且两者均呈时间依赖性。层流切应力对IL-8基因表达的诱导可能是由于NF-κB的激活。基于这些结果我们得出结论,低切应力在内皮细胞中诱导的IL-8表达可能在炎症和动脉粥样硬化的发生发展中起重要作用。