Phosphatidylethanolamines glycation, oxidation, and glycoxidation: effects on monocyte and dendritic cell stimulation

Lipid glycation is a non-enzymatic reaction between glucose and the free amino group of aminophospholipids, particularly in chronic hyperglycemia. Glycated phosphatidylethanolamine have been found in plasma and atherosclerotic plaques of diabetic patients and was correlated with increased oxidative and inflammatory stress in diabetes. However, the biological roles of glycated lipids are not fully understood. In this study, we evaluated the effect of palmitoyl-oleoyl-phosphatidylethanolamine (POPE) oxidation, glycation, and glycoxidation products on monocyte and myeloid dendritic cell stimulation. Flow cytometry analysis was used to evaluate the capability of each modified PE to induce the expression of different cytokines (IL-1β, IL-6, IL-8, MIP-1β, and TNF-α) in monocytes or myeloid dendritic cells (mDC). Our results showed that PE modifications induced different effect on the stimulation of cells producing cytokines. All PE modifications induced higher frequencies of cytokine-producing cells than basal state. Higher stimulation levels were obtained with glycated POPE, followed by glycoxidized POPE. In contrast, oxidized POPE negatively regulated the frequency of monocytes and mDC producing cytokines, when compared with non-modified POPE. In conclusion, we verified that PE glycation, compared with oxidation and glycation plus oxidation, had higher ability to stimulate monocytes and mDC. Thus detection of increased levels of PE glycation in diabetes could be considered a predictor of a inflammatory state.