Stimulation with thromboxane A2 (TXA2) receptor agonist enhances ICAM-1, VCAM-1 or ELAM-1 expression by human vascular endothelial cells.
A previous study reported that intercellular adhesion molecule-1 (ICAM-1) expression by human vascular endothelial cells (HUVEC) is augmented by intracellular signal transmission mainly through the protein kinase C (PKC) system stimulated by TXA2 receptors. In the present study, we show that a TXA2 receptor agonist, U46619, augments the expression of not only ICAM-1, but also vascular cell adhesion molecule-1 (VCAM-1) or endothelial leucocyte adhesion molecule-1 (ELAM-1) in HUVEC both at protein and mRNA levels. Pretreatment with SQ29,548 (a TXA2 receptor antagonist) or PKC inhibitors greatly diminished the extent of U46619-induced mRNA accumulation and surface expression of the adhesion molecules. An inhibitor of nuclear factor kappaB (NF-kappaB) activation, PDTC, diminishes U46619-induced VCAM-1 mRNA accumulation. NAC, which inhibits NF-kappaB and activation protein 1 (AP-1) binding activity, inhibits the expression of ICAM-1 or ELAM-1 at protein and mRNA levels. These findings suggest that ICAM-1 or ELAM-1 expression of HUVEC stimulated via TXA2 receptors is augmented by induction of NF-kappaB and AP-1 binding activity through the PKC system, and that VCAM-1 expression is augmented by induction of NF-kappaB binding activity.
Ishizuka
T
T
Division of Biomedical Engineering, National Defense Medical College Research Institute, National Defense Medical College, Tokorozawa, Saitama, Japan.
Kawakami
M
M
Hidaka
T
T
Matsuki
Y
Y
Takamizawa
M
M
Suzuki
K
K
Kurita
A
A
Nakamura
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis* / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D017482:Receptors, Thromboxane / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000276:immunology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D019040:E-Selectin; D016328:NF-kappa B; D012333:RNA, Messenger; D017482:Receptors, Thromboxane; D019010:Vascular Cell Adhesion Molecule-1; D014662:Vasoconstrictor Agents; D018799:Intercellular Adhesion Molecule-1; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid