Food-derived advanced glycation end products induce an inflammatory response in human macrophages in vitro

Abstract

Introduction and objectiveAdvanced glycation end products (AGEs) are found in processed food products. It is yet unclear whether the consumption of food-derived AGEs poses a risk for human health. Experimental studies suggest that dietary AGEs elicit inflammation. However, a clear cause-effect relationship could not be established yet and results are questioned for being caused by endotoxin. Here we investigated the effects of food-derived AGEs on the inflammatory response of human macrophages. Methodology Casein, glucose and lactose, in the proportions of milk powder, were heated at 100° up to 120 minutes. AGE-formation was monitored by fluoroscopy. Presence of endotoxin was assessed by the PYROGENT Gel Clot LAL assay. THP-1 monocytes (ATCC, TIB-202) were differentiated into macrophages and exposed to different concentrations of glycated casein with or without anti-carboxymethyl lysine (CML) antibody. Tumor necrosis factor (TNF)-alpha release was assessed by ELISA. ResultsIncrease in AGE-specific fluorescence during cooking revealed the formation of AGEs. All glycated casein and control samples did not contain endotoxin concentrations > 0.06 EU/ml. Glycated casein dose-dependently induced TNF-alpha secretion of macrophage-like cells. This effect was decreased by addition of CML-antibodies. ConclusionThese findings indicate that food-derived AGEs directly stimulate the inflammatory response of human innate immune cells.