Glycation interferes with natural killer cell function

Rosenstock, Philip; Bezold, Veronika; Bork, Kaya; Scheffler, Jonas; Horstkorte, Rüdiger

doi:10.1016/j.mad.2019.01.006

Cited by 13 publications

(7 citation statements)

References 39 publications

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“…Apoptosis assay was performed as described previously [41]. The percentage of Annexin V - / 7AAD - cells was used to determine the number of intact living cells (= non-apoptotic and non-necrotic).…”

Section: Methodsmentioning

confidence: 99%

“…Also, it has been demonstrated that MGO treatment induces activation of murine macrophages and ROS production in Sarcoma-180 bearing tumor mice [39,40], and therefore can even be beneficial for the immune system as immunomodulation against tumors. In recent studies, we could demonstrate that MGO treatment had a negative effect on the activation of human natural killer cells [41]. In the present study, we used MGO as a glycating agent and analyzed inflammatory and functional properties of human macrophages after glycation, in comparison to treatment with AGE-modified serum proteins.…”

Section: Introductionmentioning

confidence: 93%

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

Bezold

Rosenstock

Scheffler

et al. 2019

Aging

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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

Bezold

Rosenstock

Scheffler

et al. 2019

Aging

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“…In this context, glycation-induced modifications of extracellular matrix proteins resulting in intermolecular crosslinks lead to increased stiffness of tissues and vessels and affect cell migration [14]. Furthermore, there is clear evidence that glycation and AGEs lead to mitochondrial dysfunction [15,16] and impaired immune responses [17,18,19]. Glycation of growth factors such as platelet-derived growth factor (PDGF) [20] and insulin [21,22,23], as well as receptors such as nerve growth factor (NGF)-receptor [24], were reported to affect signaling functions.…”

Section: Introductionmentioning

confidence: 99%

Wnt Glycation Inhibits Canonical Signaling

Mittag

Schmidt

et al. 2019

Cells

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Glycation occurs as a non-enzymatic reaction between amino and thiol groups of proteins, lipids, and nucleotides with reducing sugars or α-dicarbonyl metabolites. The chemical reaction underlying is the Maillard reaction leading to the formation of a heterogeneous group of compounds named advanced glycation end products (AGEs). Deleterious effects have been observed to accompany glycation such as alterations of protein structure and function resulting in crosslinking and accumulation of insoluble protein aggregates. A substantial body of evidence associates glycation with aging. Wnt signaling plays a fundamental role in stem cell biology as well as in regeneration and repair mechanisms. Emerging evidence implicates that changes in Wnt/β-catenin pathway activity contribute to the aging process. Here, we investigated the effect of glycation of Wnt3a on its signaling activity. Methods: Glycation was induced by treatment of Wnt3a-conditioned medium (CM) with glyoxal (GO). Effects on Wnt3a signaling activity were analyzed by Topflash/Fopflash reporter gene assay, co-immunoprecipitation, and quantitative RT-PCR. Results: Our data show that GO-treatment results in glycation of Wnt3a. Glycated Wnt3a suppresses β-catenin transcriptional activity in reporter gene assays, reduced binding of β-catenin to T-cell factor 4 (TCF-4) and extenuated transcription of Wnt/β-catenin target genes. Conclusions: GO-induced glycation impairs Wnt3a signaling function.

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“…Recently, we could demonstrate that glycation of immune cells has a negative impact on their function [35,36]. For example, NK-cells are less active to kill tumor cells after being glycated.…”

Section: Discussionmentioning

confidence: 99%

Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells

Scheer

Bork

Simon

et al. 2020

Cells

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Neuroblastoma is the second most frequent extracranial tumor, affecting young children worldwide. One hallmark of tumors such as neuroblastomas, is the expression of polysialic acid, which interferes with adhesion and may promote invasion and metastasis. Since tumor cells use glycolysis for energy production, they thereby produce as side product methylglyoxal (MGO), which reacts with proteins to advanced glycation end products in a mechanism called glycation. Here we analyzed the expression of (poly) sialic acid and adhesion of Kelly neuroblastoma cells after glycation with MGO. We found that both sialylation and polysialylation is increased after glycation. Furthermore, glycated Kelly neuroblastoma cells had a much higher potential for migration and invasion compared with non-glycated cells.

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Glycation interferes with natural killer cell function

Cited by 13 publications

References 39 publications

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

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

Wnt Glycation Inhibits Canonical Signaling

Glycation Leads to Increased Polysialylation and Promotes the Metastatic Potential of Neuroblastoma Cells

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