Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2013, Article ID 574029, 12 pages http://dx.doi.org/10.1155/2013/574029 Research Article Resveratrol Prevents Dendritic Cell Maturation in Response to Advanced Glycation End Products Brigitta Buttari, 1 Elisabetta Profumo, 1 Francesco Facchiano, 2 Elif Inci Ozturk, 1,3 Luca Segoni, 1 Luciano Saso, 4 and Rachele Riganò 1 1 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanit` a, 299 Viale Regina Elena, 00161 Rome, Italy 2 Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanit` a, 00161 Rome, Italy 3 Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey 4 Department of Physiology and Pharmacology “Vittorio Erspamer”, La Sapienza University of Rome, 00185 Rome, Italy Correspondence should be addressed to Rachele Rigan` o; rachele.rigano@iss.it Received 1 March 2013; Revised 6 June 2013; Accepted 7 June 2013 Academic Editor: Mahesh hirunavukkarasu Copyright © 2013 Brigitta Buttari et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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 indings suggest that AGE and its receptor RAGE may be involved in the pathogenesis of autoimmune reactions through dendritic cell (DC) activation. he aim of this study was to investigate whether resveratrol, a polyphenolic antioxidant compound with tolerogenic efects on DCs, was able to counteract the mechanisms triggered by AGE/RAGE interaction on DCs. By immunochemical and cytoluorimetric 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 efect on DC surface maturation marker and RAGE up- regulation in response to AGE-albumin. It also inhibited proinlammatory cytokine expression, allostimulatory ability upregulation, mitogen-activated protein (MAP) kinases, and NF-B 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. 1. Introduction Advanced glycation end products (AGEs) are a heterogenous group of molecules that are generated through nonenzymatic glycosylation (glycation) and oxidation of proteins, lipids, and nucleic acids [1]. Even though glycation is physiologi- cally present and is modulated by several factors, disorders of glucose metabolism and systemic autoimmune diseases associated with inlammation and oxidative stress may favour the formation and accumulation of these products [2–6]. It is noteworthy that AGEs are normally produced in the body and they accumulate by age thus being considered as biomarkers of senescence [7]. Further, AGE adverse efects on cellular and tissue functions arise from their potential to cross-link intracellular and extracellular proteins thus altering their structure and function and triggering the development of diferent age-associated diseases, such as neurodegenerative and cardiovascular diseases [8, 9]. Pro- teins modiied by glycation have been shown to become antigenic thus inducing activation of immune responses [10– 12]. Six receptors that recognize and bind AGEs have been identiied [13, 14], among which the best characterized and most extensively studied receptor being RAGE, a 46-kDa protein, mainly expressed on the surface of endothelial cells, smooth muscle cells, and monocyte-derived dendritic cells (DCs) [15, 16]. Although there is accumulating evidence that AGEs are involved in senescence [9], nevertheless further investigations are needed to clarify the role of glycation in aging and aging-related diseases. It is known that the immune system undergoes continuous morphological and functional changes throughout the lifetime and gradually declines with age [17]. he decline in protective immune responses to