Advanced glycation endproducts induce self- and cross-tolerance in monocytes

• Verfasst von: Uhle, Florian [VerfasserIn]
• Verfasst von: Weiterer, Sebastian [VerfasserIn]
• Verfasst von: Siegler, Benedikt Hermann [VerfasserIn]
• Verfasst von: Brenner, Thorsten [VerfasserIn]
• Verfasst von: Lichtenstern, Christoph [VerfasserIn]
• Verfasst von: Weigand, Markus A. [VerfasserIn]
• Titel: Advanced glycation endproducts induce self- and cross-tolerance in monocytes
• Verf.angabe: Florian Uhle, Sebastian Weiterer, Benedikt Hermann Siegler, Thorsten Brenner, Christoph Lichtenstern, Markus Alexander Weigand
• E-Jahr: 2017
• Jahr: 28 June 2017
• Umfang: 8 S.
• Fussnoten: Gesehen am 27.09.2018
• Titel Quelle: Enthalten in: Inflammation research
• Ort Quelle: Cham : Springer International Publishing AG, 1969
• Jahr Quelle: 2017
• Band/Heft Quelle: 66(2017), 11, Seite 961-968
• ISSN Quelle: 1420-908X
• DOI: doi:10.1007/s00011-017-1076-9
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: AGE
• Sach-SW: Inflammation
• Sach-SW: Methylglyoxal
• Sach-SW: Sepsis
• Sach-SW: SIRS
• K10plus-PPN: 1581372159

Abstract

Introduction: Advanced glycation endproducts (AGEs) are well-known inflammatory mediators, which are recognized by immune cells through their corresponding receptor RAGE and have been shown to participate in the pathophysiology of a variety of acute as well as chronic inflammatory diseases. Nevertheless, no data are available on the aftermath of AGE recognition on immune cells. Materials and methods: We used the monocytic cell line MonoMac6 as well as primary human monocytes for double stimulation experiments. We measured secreted as well as intracellular levels of TNF-α using ELISA and flow cytometry. In addition, gene expression of surface receptors (RAGE and TLR4) and TNF were measured by qPCR. Results: Stimulation with AGE leads to a dose-dependent induction of self- and cross-tolerance in both primary monocytes as well as the MonoMac6 cell line. The AGE tolerance depended neither on a decreased expression of RAGE or TLR4, nor on a decrease of TNF-α expression. Nevertheless, intracellular TNF-α was decreased, hinting towards a posttranscriptional regulation. Conclusion: High levels of AGEs are capable to activate immune cells at first, but induce a secondary state of hypo-responsiveness in these cells. Based on the origin of its causal agent, we propose this phenomenon to be “metabolic tolerance”.