Aurintricarboxylic acid inhibits the nuclear factor-κB-dependent expression of intercellular cell adhesion molecule-1 and endothelial cell selectin on activated human endothelial cells.
Activation of the vascular endothelium and increased adhesion of circulating leukocytes to the activated endothelium are important events in inflammation and coagulation. Aurintricarboxylic acid (ATA), a triphenylmethyl dye compound, is known to inhibit platelet adhesion by interfering with the binding of von Willebrand factor to platelet glycoprotein Ib. However, the effect of ATA on the inflammatory response of endothelial cells has not yet been investigated. Here, we investigated the functional role and molecular mechanism of ATA on the activation of human endothelial cells. ATA inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), and endothelial cell selectin (E-selectin) was upregulated on human umbilical vein endothelial cells (HUVECs) in response to tumor necrosis factor-α or lipopolysaccharide (LPS). We also observed the inhibitory effect of ATA on LPS-induced mRNA expression of ICAM-1 and E-selectin. Furthermore, ATA inhibited the binding of leukocytes to activated HUVECs. ATA significantly inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and degradation of IκB on activated HUVECs, suggesting that ATA inhibits NF-κB signaling. Finally, three NF-κB inhibitors effectively inhibited the expressions of ICAM-1 and E-selectin on activated endothelial cells. The present data suggest that ATA exerts beneficial effect in various inflammation conditions through inhibition of adhesion molecule expression in activated endothelial cells and the resulting inhibition of leukocytes tissue accumulation.
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ji-Eun
JE
Kim
Sukmook
S
Lee
Kyou-Sup
KS
Han
Hyun Kyung
HK
Kim
D001312:Aurintricarboxylic Acid / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000378:metabolism
D019040:E-Selectin; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D001312:Aurintricarboxylic Acid