Shear Stress Attenuates Tumor Necrosis Factor-α-Induced Monocyte Chemotactic Protein-1 Expressions in Endothelial Cells

Jeng-Jiann Chiu ； Pei-Ling Lee ； Chih-I Lee ； Li-Jing Chen ； Cheng-Nan Chen ； Ya-Chen Ko ； Sheng-Chieh Lien

《The Chinese Journal of Physiology》 45卷4期 (2002/12) Pp. 169-176

並列摘要

The interplay between shear stress and cytokines in regulating vascular endothelial function remains largely unexplored. In the present study, the potential role of shear stress in regulating tumor necrosis factor-α (TNF-α)-induced gene expression in endothelial cells(ECs)was investigated. The TNF-α-induced monocyte chemotactic protein-1(MCP-1)mRNA expressions were significantly attenuated in ECs subjected to a high level of shear stress(20 dynes/cm^2) for 4 or 24 h prior to the addition of TNF-α in the presence of flow. Less inhibition of TNF-α-induced MCP-1 mRNA expression was found in ECs pre-exposed to a low level of shear stress(1.2 dynes/cm^2) for 24 h as compared with the cells presheared(pre-exposed to shear stress) for 4 h. Simultaneous exposure of ECs to TNF-α and a high or low level of shear stress down-regulated TNF-α-induced MCP-1 gene expressions, suggesting that the post-flow condition modulates endothelial responses to cytokine stimulation. Individually or combined, an endothelial nitric oxide synthase (eNOS) inhibitor and a glutathione(GSH) biosynthesis inhibitor had no effect on this shear stress-mediated inhibition. Moreover, in ECs either presheared or remained in a static condition prior to stimulation by TNF-α while under shear flow, the ability of TNF-α to induce AP-1-DNA binding activity in the nucleus was reduced. Our findings suggest that shear stress plays a protective role in vascular homeostasis by inhibiting endothelial responses to cytokine stimulation.

參考文獻

Noon G.P.,Hwang NHC,Normann NA, (eds.)(1976).Cardiovascular Flow Dynamics and Measurements.Baltimore, M.D.:University Park Press.

Gimbrone M.A.,Bevilacqua M.P.,Cybulsky M.I.(1990).Endothelial-dependent mechanisms of leukocyte adhesion in inflammation and atherosclerosis.Aon. N. Y. Acad. Sci..598,77-85.

Ross R.(1993).The pathogenesis of atherosclerosis: a perspective for the l990s.Nature.362,801.

Ku D.N.,Giddens D.P.,Zarins C.K.,Glagov S.(1985).Pulsatile flow and atherosclerosis in the human carotid bifurcation.Arteriosclerosis.5,293-302.

Lee D.,Chiu J.J.(1996).Intimal thickening under shear in a carotid bifurcation-a numerical study.J. Biomech.29,1-11.