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 TXA(2) 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 TXA(2) 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 kappa B (NF-kappa B) 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 TXA(2) receptors augments MCP-1 production by induction of the NF-kappa B and AP-1 binding activity through the PKC system.