Oxidized LDL-mediated monocyte adhesion to endothelial cells does not involve NFkappaB.
Oxidised LDL (oxLDL) is a key pathogenic mediator of atherogenesis, exhibiting many proatherogenic properties. We have examined the effect of oxLDL on monocyte adhesion in the endothelial cell line, EA.hy 926. This has included the role of endothelial cell adhesion molecule expression (ICAM-1 and VCAM-1), monocyte chemoattractant protein-1 (MCP-1), and the transcription factor NFkappaB in this interaction. In response to oxLDL (10-100 microg/ml), monocyte adhesion to cells increased dose-dependently. Adhesion of oxLDL at 100 microg/ml was equivalent to that seen with TNFalpha (10 ng/ml). Unmodified LDL (nLDL, 100 microg/ml) had no effect. Both oxLDL and nLDL increased MCP-1 mRNA levels. Interestingly, oxLDL had no effect on the expression of ICAM-1 and VCAM-1. In addition NFkappaB was not activated as shown by western blots of IkappaB-alpha degradation and electrophoretic mobility shift assay. In summary these data show that increased monocyte adhesion to EA.hy 926 cells occurs independently of ICAM-1, VCAM-1, and NFkappaB activation and may involve novel adhesive mechanisms.
Dwivedi
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Department of Experimental Therapeutics, William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry School, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Anggård
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Carrier
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MJ
D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D018932:Chemokine CCL2; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha