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

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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.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalChinese Journal of Physiology
Issue number4
Publication statusPublished - Dec 31 2002
Externally publishedYes



  • Cytokine
  • Endothelial cell
  • Monocyte chemotactic protein
  • Shear stress

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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