Paraoxonase 1 (PON1) reduces macrophage inflammatory responses

  • Saar Aharoni
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa 31096, Israel
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  • Michael Aviram
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa 31096, Israel
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  • Bianca Fuhrman
    Corresponding author. Tel.: +972 4 8295278; fax: +972 4 8520076.
    The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa 31096, Israel
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      • Paraoxonase 1 (PON1) directly suppresses macrophage pro-inflammatory responses in vitro and in vivo.
      • Functionally, PON1 attenuates M1-induced ROS (radical oxygen species) production, phagocytosis, and necrotic macrophage death.
      • PON1 contributes to the anti-inflammatory effect of high-density lipoprotein (HDL).
      • PON1 anti-inflammatory activity is mediated via interaction with the scavenger receptor class BI (SR-BI) independently of cholesterol efflux.



      Paraoxonase 1 (PON1) was suggested to play an anti-inflammatory role. In the present study we questioned whether PON1 has a direct impact on macrophage inflammatory responses, and the possible functional implications of such effects.

      Methods and results

      Ex-vivo studies were performed with bone marrow-derived macrophages (BMDM) harvested from C57BL/6 and human-PON1 transgenic (PON1-Tg) mice, and for the in vitro studies the J774.A1 macrophage-like cell line was used. Pro-inflammatory (M1) activation was induced by LPS and INFγ. The spontaneous and M1-induced TNFα and IL-6 secretion were significantly reduced in BMDM derived from PON1-Tg vs. C57BL/6 mice. In vitro, PON1 dose-dependently attenuated both the spontaneous and M1-induced TNFα and IL-6 secretion, and contributed to the anti-inflammatory activity of HDL. Functionally, PON1 attenuated M1-induced production of reactive oxygen species (ROS), phagocytosis, and necrotic macrophage death. PON1 anti-inflammatory activity was mediated, at least in part, via binding to SR-BI, but was independent of the enzyme catalytic activity or of cholesterol efflux stimulation, and did not involve binding to ABCA1.


      The present study demonstrates, for the first time, that PON1 directly suppresses macrophage pro-inflammatory responses. These findings suggest that PON1 decreases sustained pro-inflammatory reactions, which subsequently can attenuate plaque progression.


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