Shear Stress Increases ICAM-1 and Decreases VCAM-1 and E-selectin Expressions Induced by Tumor Necrosis Factor-α in Endothelial Cells

Jeng Jiann Chiu, Pei Ling Lee, Cheng Nan Chen, Chih I. Lee, Shun Fu Chang, Li Jing Chen, Sheng Chieh Lien, Ya Chen Ko, Shunichi Usami, Shu Chien

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

Objective-Vascular endothelial cells (ECs) are subjected to shear stress and cytokine stimulation. We studied the interplay between shear stress and cytokine in modulating the expression of adhesion molecule genes in ECs. Methods and Results-Shear stress (20 dynes/cm2) was applied to ECs prior to and/or following the addition of tumor necrosis factor (TNF)-α. Shear stress increased the TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-α-induced expression of vascular adhesion molecule-1 (VCAM-1) and E-selectin. Transfection studies using promoter reporter gene constructs of ICAM-1, VCAM-1, and E-selectin demonstrated that these shear stress modulations of gene expression occur at the transcriptional levels. After 24-hour preshearing followed by 1 hour of static incubation, the effect of preshearing on TNF-α-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-α-induced VCAM-1 and E-selectin mRNA expressions following preshearing, however, required a static incubation time of >6 hours (complete recovery at 24 hours). Pre- and postshearing caused a reduction in the nuclear factor-κB-DNA binding activity induced by TNF-α in the EC nucleus. Conclusions-Our findings suggest that shear stress plays differential roles in modulating the TNF-α-induced expressions of ICAM-1 versus VCAM-1 and E-selectin genes in ECs.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2004
Externally publishedYes

Keywords

  • Cytokine
  • E-selectin
  • Endothelial cell
  • Intercellular adhesion molecule-1
  • Shear stress
  • Vascular adhesion molecule-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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