AGE-BSA induces immunological tolerance in the monocytic Mono Mac 6 cell line

Abstract

Event Abstract Back to Event AGE-BSA induces immunological tolerance in the monocytic Mono Mac 6 cell line Florian Uhle1*, Ilona Magel1 and Markus A. Weigand1 1 Justus-Liebig-University Giessen, Department of Anaesthesiology and Critical Care Medicine, Germany The induction of immunological tolerance is an important negative feedback mechanism to control activated innate immune cells and thereby prevents excessive inflammation. The phenomenon of self- and cross-tolerance induction has been described so far for a variety of ligands and their corresponding pattern recocgnition receptors. We were interested to assess the capability of different ligands of the Receptor for Advanced Glycation Endproducts (RAGE) to induce tolerance. An initial screening of the monocytic cell line MonoMac-6 using a variety of immune receptor agonists revealed a tolerance induction, beside others, by the RAGE ligand advanced glycation endproduct-modified bovine serum albumin (AGE-BSA), measurable by a diminished TNF-alpha secretion in response to a second stimulation. The effect was specific for AGE-modified BSA, as unmodified BSA did not mediate the effect. In contrast to AGE-BSA, the RAGE ligand HMGB-1, neither in its chemokine nor in its oxidated cytokine conformation, lead to an induction of tolerance. The tolerance induction was not accompanied by a decrease, but rather with a slight increase of receptor expression as assessed by quantitative RT-PCR. To exclude the possibility, that induction of apoptosis or modulation of the cell cycle might be the reason for the altered response, we assessed both using flow cytometry and found no agonist-induced changes. Interestingly, while LPS was capable to induce tolerance in minute amounts (0,1ng/ml), higher levels of AGE-BSA (≥10µg/ml) were necessary. Furthermore, a comprehensive gene expression analysis using qPCR arrays targeting signaling molecules did not bring any evidence for a downregulation of any of the possible signaling cascades involved. Additional gene expression analysis for the TNF gene revealed a diminished expression of the transcipt after an initial treatment with both, LPS or AGE-BSA. In conclusion, we have evidence for an AGE-BSA-mediated tolerance induction in monocytic cells, which seems to be independent of expression changes of RAGE and downstream signaling molecules. Nevertheless, the regulation seems to happen on the level of expression and further work is necessary to reveal, which mechanisms are involved and how this findings translate into the in vivo-situation. Keywords: RAGE receptor, Advanced glycation end products, tolerance, Monocytes, Inflammation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Uhle F, Magel I and Weigand MA (2013). AGE-BSA induces immunological tolerance in the monocytic Mono Mac 6 cell line. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01097 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Mr. Florian Uhle, Justus-Liebig-University Giessen, Department of Anaesthesiology and Critical Care Medicine, Giessen, Germany, florian.uhle@chiru.med.uni-giessen.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Florian Uhle Ilona Magel Markus A Weigand Google Florian Uhle Ilona Magel Markus A Weigand Google Scholar Florian Uhle Ilona Magel Markus A Weigand PubMed Florian Uhle Ilona Magel Markus A Weigand Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.