Paraoxonase 1 (PON1) reduces macrophage inflammatory responses.

摘要: Abstract Objectives 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 possible functional implications of such effects. Methods results Ex-vivo studies were performed with bone marrow-derived macrophages (BMDM) harvested from C57BL/6 human-PON1 transgenic (PON1-Tg) mice, for in vitro J774.A1 macrophage-like cell line used. Pro-inflammatory (M1) activation induced by LPS INFγ. The spontaneous M1-induced TNFα IL-6 secretion significantly reduced in BMDM derived PON1-Tg vs. mice. In vitro, dose-dependently attenuated both secretion, contributed activity HDL. Functionally, production reactive oxygen species (ROS), phagocytosis, necrotic death. mediated, at least part, via binding SR-BI, but independent enzyme catalytic or cholesterol efflux stimulation, did not involve ABCA1. Conclusions demonstrates, first time, that directly suppresses pro-inflammatory responses. These findings suggest decreases sustained reactions, which subsequently can attenuate plaque progression.