title: Triggering of inflammatory response by myeloperoxidase-oxidized LDL.
abstract: The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-alpha by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 microg/mL and 200 microg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 microg/mL) increased the production of TNF-alpha 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.
authors.affiliation: Experimental Medicine Laboratory. Université de Bruxelles, Unit 222, ISPPC, CHU André Vésale, 706, route de Gozée, 6110 Montigny-Le-Tilleul, Belgium. karim.zouaoui@chu.charleroi.be
authors.forename: Karim Zouaoui
authors.initials: KZ
authors.lastname: Boudjeltia
authors.forename: Ilham
authors.initials: I
authors.lastname: Legssyer
authors.forename: Pierre
authors.initials: P
authors.lastname: Van Antwerpen
authors.forename: Roger Lema
authors.initials: RL
authors.lastname: Kisoka
authors.forename: Sajida
authors.initials: S
authors.lastname: Babar
authors.forename: Nicole
authors.initials: N
authors.lastname: Moguilevsky
authors.forename: Paul
authors.initials: P
authors.lastname: Delree
authors.forename: Jean
authors.initials: J
authors.lastname: Ducobu
authors.forename: Claude
authors.initials: C
authors.lastname: Remacle
authors.forename: Michel
authors.initials: M
authors.lastname: Vanhaeverbeek
authors.forename: Dany
authors.initials: D
authors.lastname: Brohee
mesh_terms: D000418:Albumins / Q000378:metabolism; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology*; D016209:Interleukin-8 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000502:physiology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism* / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000418:Albumins; D018836:Inflammation Mediators; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D003300:Copper; D009195:Peroxidase