Thromboxane A2 (TXA2) receptor blockade suppresses monocyte chemoattractant protein-1 (MCP-1) expression by stimulated vascular endothelial cells.
In a previous study, it was reported that stimulation with a TXA2 receptor agonist, U46619, augments the expression of adhesion molecules by human umbilical vein endothelial cells (HUVEC). In the present study we showed that U46619 augments the expression of MCP-1 in HUVEC, both at the protein and mRNA levels. Pretreatment with TXA2 receptor antagonists greatly diminishes the extent of tumour necrosis factor-alpha (TNF-alpha)-, platelet-activating factor (PAF)-, or U46619-induced mRNA accumulation and production of MCP-1. Protein kinase C (PKC) inhibitors diminish U46619-induced mRNA accumulation and production of MCP-1. NAC, which inhibits nuclear factor kappaB (NF-kappaB) activation and activating protein 1 (AP-1) binding activity, inhibits the expression of MCP-1 at the protein and mRNA levels. These results indicate that in HUVEC stimulation via the TXA2 receptors augments MCP-1 production by induction of the NF-kappaB and AP-1 binding activity through the PKC system.
Ishizuka
T
T
Division of Biomedical Engineering, National Defence Medical College Research Institute, Tokorozawa, Saitama, and Bayer Yakuhin Ltd, Osaka, Japan.
Sawada
S
S
Sugama
K
K
Kurita
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013928:Thromboxane A2 / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014471:Umbilical Veins; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D017482:Receptors, Thromboxane; D014157:Transcription Factors; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011493:Protein Kinase C