title: The anti-inflammatory effect of paraoxonase 1 against oxidized lipids depends on its association with high density lipoproteins.
abstract: OBJECTIVE
  The aims of this study were to investigate whether purified PON1 can reduce the pro-inflammatory effect of oxidized phospholipids and whether the effect depended on its association with HDL.
  
  
  METHODS
  Lipid peroxidation was induced by copper ions and was measured using the conjugated diene method. Lysophosphatidylcholine (lyso-PC) formation was measured by HPLC with evaporative light scattering detection (ELSD) and ICAM-1 expression on Ea.hy926 endothelial cells was analyzed by flow cytometry.
  
  
  RESULTS
  Purified PON1 significantly inhibited copper-induced oxidation of LDL and HDL, causing a 60.5% and 77.7% decrease in conjugated diene formation, respectively. Incubating PON1 with oxLDL caused a significant increase in lyso-PC levels, while oxHDL caused a significant decrease. PON1 (12.5 to 50 μg/mL) had a pro-inflammatory effect in the presence of oxLDL, increasing ICAM-1 levels in Ea.hy926 cells by 33.0% and 40.6% (p<0.001) respectively, and had an anti-inflammatory effect in the presence of oxHDL, causing a 3-fold reduction in ICAM-1 levels. PON1 also caused a significant decrease in TNFα and purified lyso-PC-induced ICAM-1 expression. The results obtained with reconstituted HDL as well as LCAT and PAF-AH inhibitors suggested that the anti-inflammatory effect of PON1 against oxidized lipids is dependent on its association with HDL.
  
  
  CONCLUSIONS
  Our results clearly showed that PON1 is involved in the anti-inflammatory effect of HDL and that the effect appears to depend on its association with HDL.
authors: Research Center on Aging, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors: Soumaya
authors: S
authors: Loued
authors: Maxim
authors: M
authors: Isabelle
authors: Hicham
authors: H
authors: Berrougui
authors: Abdelouahed
authors: A
authors: Khalil
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D043303:Aryldialkylphosphatase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015227:Lipid Peroxidation / Q000502:physiology*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D018799:Intercellular Adhesion Molecule-1; D043303:Aryldialkylphosphatase