The in vitro effect of myeloperoxidase modified LDL on THP-1 derived macrophages

Abstract

Background and Aims: Atherosclerosis is a chronic inflammatory disorder characterized by the accumulation of lipids and inflammatory cells inside the intima of arteries. Macrophages (Mφs) play a crucial role in the development of the disease by engulfing modified LDL particles and forming foam cells which constitute the hallmark of atherosclerosis. Many studies suggest that myeloperoxidase oxidized LDL (Mox-LDL) is an important patho-physiological model for LDL modification in vivo. Classically activated (M1) and alternatively activated (M2) Mφs are both implicated in the process of atherogenesis. Since little is known about the effects of Mox-LDL on Mφ biology and pathobiology, 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 Mφs.

Methods: THP-1 monocytes were differentiated into M0-Mφs by treatment with phorbol12-myristate-13-acetate. Resting M0-Mφs were polarized toward M1- and M2-Mφs, then M0-, M1- and M2-Mφs were all treated with physiological concentrations of Mox-LDL in order to assess the effect of Mox-LDL treatment on Mφ polarization and repolarization as well as on the level of ROS generation and cholesterol uptake.

Results: Treatment of M0-Mφs with a physiological concentration of Mox-LDL had no significant effects at the level of their polarization. However, treatment of M1-Mφs with Mox-LDL resulted in a significant reduction in their IL-10 cytokine secretion with no significant effects at the level of ROS generation and cholesterol uptake.

Conclusions: Our results point to a potential role of Mox-LDL in increasing the pro-inflammatory state in Mφs through reducing the release of the anti-inflammatory cytokine IL-10.