流体切应力作用强度对内皮细胞IL-8生成的影响

Force-dependent Effects of Interleukin-8 Production in Endothelial Cells Exposed to Fluid Shear Stress

血管内皮细胞衬于血管腔的表面 ,是血流机械应力的主要感受者。切应力可以直接调节内皮细胞生物活性物质的合成和分泌 ,其中包括诱导内皮细胞生成 IL- 8,而且 IL- 8的生成量与切应力作用时间有关。为阐明内皮细胞 IL- 8的生成除了与切应力的作用时间有关外还与切应力的强度有关 ,我们用不同强度的流体切应力 (2 .0 9、4 .6 1、6 .19、8.5 1、10 .5 0、12 .5 9、14 .4 1、17.2 2、18.32 dyne/ cm2 )处理培养的人脐静脉内皮细胞 ,然后采用双抗体夹心 ABC- EL ISA技术检测内皮细胞 IL - 8蛋白质的生成。结果显示 :未用切应力处理的内皮细胞只有极少量的 IL - 8蛋白质生成 ;切应力处理内皮细胞后 ,低切应力 (2 .0 9dyne/ cm2 )时 IL - 8蛋白质生成量明显增加 ,约为高切应力(18.32 dyne/ cm2 )时 IL - 8蛋白质生成量的 6 (作用 5 h)或 7倍 (作用 6 h)。 IL - 8蛋白质生成量与内皮细胞所施加的切应力强度呈反变关系 ;直线回归方程 :5 h时为 y=76 0 .12 - 36 .0 6 x,相关系数 γ=- 0 .978;6 h时为 y=781.87-36 .6 6 x,相关系数 γ=- 0 .980。式中 :y为切应力作用下内皮细胞 IL- 8的生成量 ;x为施加于内皮细胞的切应力强度 (dyne/ cm2 )。不同的切应力作用时间 (5 h、6 h)均表现出相同的 IL- 8蛋白质生成量随切?

Fluid shear stress plays a key role in many physiological activities and pathological processes of the cardiovascular diseases. In vivo, endothelial cells (ECs) are constantly exposed to hemodynamic force which can modulate structure and function of ECs. Previous studies have demonstrated that IL-8 protein production in endothelial cells was modulated by fluid shear stress, and IL-8 protein production induced by fluid shear stress was time-dependent. In order to identify the role of intensity of fluid shear stress on IL-8 protein production of human umbilical vein endothelial cells (HUVECs), we had HUVECs exposed to shear stress 2.09,4.61,6.19,8.51,10.50,12.59,14.41,17.22,18.32 dyne/cm 2 respectively and employed quantitative sandwich enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 protein. Here we show that HUVECs untreated with fluid shear stress secreted very little IL-8 in culture media. The IL-8 protein production induced by shear stress was force intensity-dependent. After HUVECs being subjected to low fluid shear stress (2.09 dyne/cm 2)for 5h or 6h, IL-8 protein production increased and was nearly 6 times or 7 times over that of HUVECs subjected to high fluid shear stress (18.32 dyne/cm 2). The linear regression equations between IL-8 protein production (y) and shear stress (dyne/cm 2, x) are y=760.12-36.06x, γ=-0.978(for 5 h); y=781.87-36.66x, γ=-0.980(for 6 h). This in vitro study demonstrates that the production of IL-8 can be regulated by fluid shear stress, and the production of IL-8 induced by shear stress is not only time-dependent but also force intensity-dependent. These observations suggest that the low fluid shear stress induces much more IL-8 secretion, which may play an important role in the pathogenesis and development of both inflammation and atherosclerosis.