HUVECs were pretreated with 50 ¦ÌM CORM-2 for 3 hours, and stimulated with tumor necrosis factor-¦Á (TNF-¦Á, 10 ng/ml) for an additional 0-5 hours. PBMCs were pretreated with 50-100 ¦ÌM CORM-2 for 1hour followed by stimulating with lipopolysaccharid (LPS, 10 ng/ml) for additional 0-9 hours. The mRNA and protein levels were determined by RT-PCR and western blotting, respectively.
Pretreatment with CORM-2 significantly inhibited TNF-¦Á-induced TF and PAI-1 up-regulation in HUVECs, and LPS-induced TF expression in PBMCs. CORM-2 inhibited TNF-¦Á-induced activation of p38 MAPK, ERK1/2, JNK, and NF-¦ÊB signaling pathways in HUVECs.
CORM-2 suppresses TNF-¦Á-induced TF and PAI-1 up-regulation, and MAPKs and NF-¦ÊB signaling pathways activation by TNF-¦Á in HUVECs. CORM-2 suppresses LPS-induced TF up-regulation in PBMCs. Therefore, we envision that the antithrombotic activity of CORM-2 might be used as a pharmaceutical agent for the treatment of various inflammatory conditions.