Triggering of inflammatory response by myeloperoxidase-oxidized LDL.
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.
Boudjeltia
Karim Zouaoui
KZ
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
Legssyer
Ilham
I
Van Antwerpen
Pierre
P
Kisoka
Roger Lema
RL
Babar
Sajida
S
Moguilevsky
Nicole
N
Delree
Paul
P
Ducobu
Jean
J
Remacle
Claude
C
Vanhaeverbeek
Michel
M
Brohee
Dany
D
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
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