Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-[alpha] in endothelial cells.
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.


RESULTS
Shear stress (20 dynes/cm2) was applied to ECs prior to and/or following the addition of tumor necrosis factor (TNF)-alpha. Shear stress increased the TNF-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) at both mRNA and surface protein levels, but decreased the TNF-alpha-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-alpha-induced ICAM-1 mRNA expression vanished. The recovery of the TNF-alpha-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-kappaB-DNA binding activity induced by TNF-alpha in the EC nucleus.


CONCLUSIONS
Our findings suggest that shear stress plays differential roles in modulating the TNF-alpha-induced expressions of ICAM-1 versus VCAM-1 and E-selectin genes in ECs.
Chiu
Jeng-Jiann
JJ
Division of Medical Engineering Research, National Health Research Institutes, Taipei 114, Taiwan, ROC. jjchiu@nhri.org.tw
Lee
Pei-Ling
PL
Chen
Cheng-Nan
CN
Lee
Chih-I
CI
Chang
Shun-Fu
SF
Chen
Li-Jing
LJ
Lien
Sheng-Chieh
SC
Ko
Ya-Chen
YC
Usami
Shunichi
S
Chien
Shu
S
D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
D019040:E-Selectin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004247:DNA