Research Paper Volume 11, Issue 14 pp 5258—5275

Glycation of macrophages induces expression of pro-inflammatory cytokines and reduces phagocytic efficiency

Veronika Bezold 1, , Philip Rosenstock 1, , Jonas Scheffler 1, , Henriette Geyer 2, , Rüdiger Horstkorte 1, , Kaya Bork 1, ,

  • 1 Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
  • 2 Octapharma Biopharmaceuticals GmbH, Molecular Biochemistry, Berlin, Germany

received: March 14, 2019 ; accepted: July 21, 2019 ; published: July 29, 2019 ;

https://doi.org/10.18632/aging.102123
How to Cite

Copyright © 2019 Bezold et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Glycation and the accumulation of advanced glycation end products (AGEs) are known to occur during normal aging but also in the progression of several diseases, such as diabetes. Diabetes type II and aging both lead to impaired wound healing. It has been demonstrated that macrophages play an important role in impaired wound healing, however, the underlying causes remain unknown. Elevated blood glucose levels as well as elevated methylglyoxal (MGO) levels in diabetic patients result in glycation and increase of AGEs. We used MGO to investigate the influence of glycation and AGEs on macrophages. We could show that glycation, but not treatment with AGE-modified serum proteins, increased expression of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-8 but also affected IL-10 and TNF-α expression, resulting in increased inflammation. At the same time, glycation reduced phagocytic efficiency and led to impaired clearance rates of invading microbes and cellular debris. Our data suggest that glycation contributes to changes of macrophage activity and cytokine expression and therefore could support the understanding of disturbed wound healing during aging and diabetes.

Abbreviations

AGEs: advanced glycation end products; DMSO: dimethyl sulfoxide; FCS: fetal calf serum; AGE-FCS: glycated FCS; H2O2: hydrogen peroxide; IFN: interferon; IL: interleukin; LCIS: live cell imaging solution; LPS: lipopolysaccharide; MGO: methylglyoxal; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NF-κB: nuclear transcription factor κB; PMA: 12-myristate 13-acetate; qPCR: quantitative real-time PCR; RAGE: receptor for advanced glycation end products; ROS: reactive oxygen species; RPL32: ribosomal protein L32; SD: standard deviation; β-ME: β-mercaptoethanol; H2DCFDA: 2',7'-dichlorodihydrofluorescein diacetate; 7AAD: 7-aminoactinomycin.