流体切应力作用时间对内皮细胞IL-8生成的影响

Time-dependent Increase of Interleukin-8 Production in Endothelial Cells Exposed to Fluid Shear Stress

内皮细胞对力学刺激反应敏感 ,流体切应力可以直接调节内皮细胞生物活性物质的产生。为阐明内皮细胞白细胞介素 - 8(IL- 8)蛋白质的生成受力学因素的影响 ,本文用流体切应力 (2 .0 9、4 .6 1、6 .19dyne/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 1h,IL- 8蛋白质生成增加 ,处理 5 hIL- 8蛋白质生成量至最高值 ,处理 8h IL- 8蛋白质生成量下降 ,10 h后 IL- 8蛋白质维持在一个较高的水平 ;各实验组 (2 .0 9、4 .6 1、6 .19dyne/cm2 )均表现出相同的 IL- 8蛋白质随力学刺激时间的变化规律。提示流体切应力确实可以诱导内皮细胞生成 IL- 8,并且 IL- 8的生成量与切应力的作用时间有关 ,呈双相性变化。流体切应力诱导内皮细胞生成 IL- 8,可能在急性炎症或动脉粥样硬化的发生。

Fluid shear stress plays an important role in many physiological and pathological processes of the cardiovascular system. Being constantly exposed to mechanical shear stress, vascular endothelial cells can sense the changes of blood flow forces and regulate vascular structure and function. Previous studies demonstrated that IL-8 mRNA expression in endothelial cells was modulated by fluid shear stress. To identify the effect of fluid shear stress on IL-8 protein production of human umbilical vein endothelial cells (HUVECs), we employed quantitative sandwich enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 protein. It was found that the HUVECs not treated with fluid shear stress secreted very little IL-8 in culture media. Howerer, after 1 hour of exposure to shear stress, the secretion of IL-8 increased; at 5 hours of exposure, the seceretion reached the summit; at 8 hours of exposure, the secretion of IL-8 decreased and then remained at a constant level till the end (12 hours) of the experiment. The increase of IL-8 secretion induced by shear stress was time-dependent. The biphasic response of IL-8 protein production was found in experiments in which the shear stress applied was 2.09 dyne/cm 2, 4.61 dyne/cm 2, and 6.19dyne/cm 2. The IL-8 protein production in response to shear stress was very similar to the IL-8 gene expression in response to shear stress,and had the obvious delay. The induction of IL-8 protein production by fluid shear stress is probably due to the gene expression. This in vitro study demonstrates that the production of IL-8 can be regulated by fluid shear stress. Fluid shear stress induces a biphasic response of human HUVECs' production of IL-8 protein. These observations suggest that the process of the fluid shear stress induced HUVECs' production of IL-8 may play an important role in the genesis and development of both inflammation and atherosclerosis.