Resveratrol prevents dendritic cell maturation in response to advanced glycation end products.
Advanced glycation end products (AGEs), generated through nonenzymatic glycosylation of proteins, lipids, and nucleic acids, accumulate in the body by age thus being considered as biomarkers of senescence. Senescence is characterized by a breakdown of immunological self-tolerance, resulting in increased reactivity to self-antigens. Previous findings suggest that AGE and its receptor RAGE may be involved in the pathogenesis of autoimmune reactions through dendritic cell (DC) activation. The aim of this study was to investigate whether resveratrol, a polyphenolic antioxidant compound with tolerogenic effects on DCs, was able to counteract the mechanisms triggered by AGE/RAGE interaction on DCs. By immunochemical and cytofluorimetric assays, we demonstrated that in vitro pretreatment of human monocyte-derived DCs with resveratrol prevents DC activation in response to glucose-treated albumin (AGE-albumin). We found that resveratrol exerts an inhibitory effect on DC surface maturation marker and RAGE up-regulation in response to AGE-albumin. It also inhibited proinflammatory cytokine expression, allostimulatory ability upregulation, mitogen-activated protein (MAP) kinases, and NF-κB activation in AGE-albumin-stimulated DCs. We suggest that resveratrol, by dismantling AGE/RAGE signaling on DCs may prevent or reduce increased reactivity to self-molecules in aging.
Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, 299 Viale Regina Elena, 00161 Rome, Italy.
Brigitta
B
Buttari
Elisabetta
E
Profumo
Francesco
F
Facchiano
Elif Inci
EI
Ozturk
Luca
L
Segoni
Luciano
L
Saso
Rachele
R
Riganò
D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D002850:Chromatography, Gel; D019295:Computational Biology; D003713:Dendritic Cells / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D017127:Glycation End Products, Advanced; D013267:Stilbenes; D005947:Glucose; D000077185:Resveratrol