Advanced glycation endproducts induce self- and cross-tolerance in monocytes
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. Neverthe...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
28 June 2017
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| In: |
Inflammation research
Year: 2017, Volume: 66, Issue: 11, Pages: 961-968 |
| ISSN: | 1420-908X |
| DOI: | 10.1007/s00011-017-1076-9 |
| Online Access: | Verlag, Pay-per-use, Volltext: http://dx.doi.org/10.1007/s00011-017-1076-9 Verlag, Pay-per-use, Volltext: https://doi.org/10.1007/s00011-017-1076-9 
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| Author Notes: | Florian Uhle, Sebastian Weiterer, Benedikt Hermann Siegler, Thorsten Brenner, Christoph Lichtenstern, Markus Alexander Weigand |
| Summary: | 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”. |
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| Item Description: | Gesehen am 27.09.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1420-908X |
| DOI: | 10.1007/s00011-017-1076-9 |