The effect of 5,8,11,14-eicosatetraynoic acid on endothelial cell gene expression.
The endothelium plays a key role in inflammation, hemostasis and organ rejection. We report here that a synthetic polyunsaturated fatty acid, 5,8,11,14-eicosatetraynoic acid (ETYA), selectively inhibits the up-regulation of several genes on endothelial cells. ETYA suppresses endothelial cell activation by inhibiting the up-regulation of adhesion molecules like E-selectin. A runoff assay for E-selectin demonstrated that the suppression is at the level of transcription. The fact that ETYA inhibits E-selectin upon stimulation with a diverse group of stimuli like lipopolysaccharide, tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate, suggests that ETYA does not exert its effect by modifying membrane-bound receptors. The messenger RNA for interleukin-8 and glyceraldehyde phosphate dehydrogenase are not affected. Pre-treatment of endothelial cells with ETYA also prevents the adherence of monocytes to tumor necrosis factor-alpha-stimulated cells.
Stuhlmeier
K M
KM
Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. kstuhlm@bidmc.harvard.edu
Tarn
C
C
Bach
F H
FH
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D015342:DNA Probes / Q000235:genetics; D019040:E-Selectin / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D015342:DNA Probes; D019040:E-Selectin; D016209:Interleukin-8; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D015117:5,8,11,14-Eicosatetraynoic Acid; D018799:Intercellular Adhesion Molecule-1