Published online before print November 13, 2003, doi: 10.1161/01.ATV.0000106321.63667.24
© 2004 American Heart Association, Inc.
Vascular Biology |
Shear Stress Increases ICAM-1 and Decreases VCAM-1 and E-selectin Expressions Induced by Tumor Necrosis Factor-
in Endothelial Cells
From the Division of Medical Engineering Research (J.-J.C., P.-L.L., C.-N.C., C.-I.L., S.-F.C., L.-J.C., S.-C.L., Y.-C.K.) National Health Research Institutes, Taiwan, R.O.C. Institute of Biomedical Engineering (J.-J.C.), National Yang-Ming University, Taiwan, R.O.C. Department of Radiological Technology (Y.-C.K.), Yuanpei University of Science and Technology, Taiwan, R.O.C. Department of Bioengineering and Whitaker Institute of Biomedical Engineering (S.U., S.C.), University of California, San Diego, Calif.
Correspondence to Jeng-Jiann Chiu, Ph.D., Division of Medical Engineering Research, National Health Research Institutes, Taipei 114, Taiwan, R.O.C. E-mail jjchiu{at}nhri.org.tw
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)-
. Shear stress increased the TNF-–induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-–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-–induced ICAM-1 mRNA expression vanished. The recovery of the TNF-–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-
B-DNA binding activity induced by TNF- in the EC nucleus.
Conclusions— Our findings suggest that shear stress plays differential roles in modulating the TNF-–induced expressions of ICAM-1 versus VCAM-1 and E-selectin genes in ECs.
Key Words: cytokine • E-selectin • endothelial cell • intercellular adhesion molecule-1 • shear stress • vascular adhesion molecule-1
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