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Thromboxane A2 (TXA2) receptor blockade suppresses monocyte chemoattractant protein-1 (MCP-1) expression by
T Ishizuka1, S Sawada, K Sugama
1Division of Biomedical Engineering, National Defence Medical College Research Institute, Tokorozawa, Saitama, and Bayer Yakuhin Ltd, Osaka, Japan.
Abstract:
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.