title: Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells.
abstract: The upregulation of endothelial cell MCP-1 production by ox-LDL is a major initiating event in atherogenesis. HDL and PON1 retard the oxidation of LDL and therefore may retard endothelial cell MCP-1 production. The endothelial cell line EAhy926 was incubated with ox-LDL in the presence and absence of HDL and PON1 and the production of MCP-1 was measured by ELISA. Human HDL and PON1 significantly inhibited the in vitro oxidation of LDL and completely prevented the ox-LDL induced increase in MCP-1 production by endothelial cells. Ostrich HDL that does not contain PON1 was unable to prevent LDL-oxidation or the production of MCP-1 by endothelial cells. PON1 attenuates the ox-LDL induced MCP-1 production by endothelial cells. This is one, early, mechanism by which PON1 may be anti-atherogenic.
authors.affiliation: Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK. bharti.mackness@cmmc.nhs.uk
authors.forename: Bharti
authors.initials: B
authors.lastname: Mackness
authors.forename: David
authors.initials: D
authors.lastname: Hine
authors.forename: Yifen
authors.initials: Y
authors.lastname: Liu
authors.forename: Maria
authors.initials: M
authors.lastname: Mastorikou
authors.forename: Mike
authors.initials: M
authors.lastname: Mackness
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D004347:Drug Interactions; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D008054:Lipid Peroxides; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D043303:Aryldialkylphosphatase