The effect of myeloperoxidase-oxidized LDL on THP-1 macrophage polarization and repolarization

Macrophages (M phi s) play a crucial role in the development of atherosclerosis by engulfing modified LDL particles and forming foam cells, the hallmark of atherosclerosis. Many studies suggest that myeloperoxidase-oxidized LDL (Mox-LDL) is an important pathophysiological model for LDL modification in vivo. Classically (M1) and alternatively activated (M2) M phi s are both implicated in the process of atherogenesis. M phi s are highly plastic cells whereby they undergo repolarization from M1 to M2 and vice versa. Since little is known about the effects of Mox-LDL on M phi polarization and repolarization, our study aimed at evaluating the in vitro effects of Mox-LDL at this level through making use of the well-established model of human THP-1-derived M phi s. Resting M0-M phi s were polarized toward M1- and M2-M phi s, then M0-, M1- and M2-M phi s were all treated with physiological concentrations of Mox-LDL to assess the effect of Mox-LDL treatment on M phi polarization and repolarization. Treatment of M0-M phi s with a physiological concentration of Mox-LDL had no significant effects at the level of their polarization. However, treatment of M1-M phi s with Mox-LDL resulted in a significant reduction in their IL-10 cytokine secretion. Our results point to a potential role of Mox-LDL in increasing the pro-inflammatory state in M phi s through reducing the release of the anti-inflammatory cytokine, IL-10.