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

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

doi:10.18632/aging.102123

Cited by 36 publications

(29 citation statements)

References 65 publications

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“…The mutation of Nox2 or silenced p47 has been shown to inhibit NADPH oxidase to reduce the production of extracellular ROS, favoring the macrophage poise towards the M2 phenotype ( 117 ). An elevated MGO usually results in glycation and the increase of AGEs ( 118 ). Macrophages express M1 phenotype markers and secrete proinflammatory cytokines after treatment with AGE through activation of the MAPK pathway.…”

Section: Systemic and Local Factors Of Macrophage Dysfunction In Non-healing Woundsmentioning

confidence: 99%

Macrophage Related Chronic Inflammation in Non-Healing Wounds

et al. 2021

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Persistent hyper-inflammation is a distinguishing pathophysiological characteristic of chronic wounds, and macrophage malfunction is considered as a major contributor thereof. In this review, we describe the origin and heterogeneity of macrophages during wound healing, and compare macrophage function in healing and non-healing wounds. We consider extrinsic and intrinsic factors driving wound macrophage dysregulation, and review systemic and topical therapeutic approaches for the restoration of macrophage response. Multidimensional analysis is highlighted through the integration of various high-throughput technologies, used to assess the diversity and activation states as well as cellular communication of macrophages in healing and non-healing wound. This research fills the gaps in current literature and provides the promising therapeutic interventions for chronic wounds.

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Section: Systemic and Local Factors Of Macrophage Dysfunction In Non-healing Woundsmentioning

confidence: 99%

Macrophage Related Chronic Inflammation in Non-Healing Wounds

et al. 2021

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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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“… 28 Diabetic mouse models have implicated chronic hyperglycemia in reduced recruitment of neutrophils from the vascular compartment in to infected tissue. 28 , 29 Glycated macrophages have been shown to have reduced phagocytic capacity in the setting of chronically elevated blood glucose levels, 30 likely contributing to decreased clearance of viral infections. 31 Glycation of complement decreases fixation to IgG needed for antibody-mediated virus neutralization, 32 and presumably would be worse in patients with higher baseline HbA1c.…”

Section: Discussionmentioning

confidence: 99%

Elevated glycohemoglobin is linked to critical illness in COVID-19: a retrospective analysis

Windham

Wilson

Fling

et al. 2021

Therapeutic Advances in Infection

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Background: Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission. Methods: The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included. Demographics, comorbidities, and select medications were collected by chart abstraction. Missing height for calculating body mass index (BMI) was imputed using the median height for patients’ sex and race/ethnicity. Adjusted odds ratios (aOR) were estimated using multivariable logistic regression and a minimax concave penalty (MCP) regularized logistic regression explored prediction. Results: Participants had a mean [standard deviation (SD)] age 55 (17), BMI 30.9 (8.2), 55% were male and 80% were ethnic/racial minorities. Increasing age [aOR: 1.24 (1.07, 1.45) per 10 years], higher BMI (aOR 1.03 (1.00, 1.06), and poorly controlled diabetes [hemoglobin A1C (HbA1c) ⩾ 8] (aOR 2.26 (1.24, 4.12) were significantly ( p < 0.05) associated with greater odds of intubation or death. Female sex [aOR: 0.63, 95% CI (0.40, 0.98); p value = 0.043] was associated with lesser odds of intubation or death. The odds of death and/or intubation increased 19% for every 1 unit increase in HbA1c value [OR: 1.19 (1.01, 1.43); p = 0.04]. Our final MCP model included indicators of A1C ⩾ 8, age > 65, sex, and minority status, but predicted intubation/death only slightly better than random chance [area under the receiver operating characteristic curve (AUC) = 0.61 (0.56, 0.67)]. Conclusion: In a hospitalized patient cohort with COVID-19, worsening control of diabetes as evidenced by higher HbA1c was associated with increased risk of intubation or death within 7 days of admission. These results complement and help clarify previous associations found between diabetes and acute disease in COVID-19. Importantly, our analysis is missing some known predictors of severity in COVID-19. Our predictive model had limited success, suggesting unmeasured factors contribute to disease severity differences.

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

Cited by 36 publications

References 65 publications

Macrophage Related Chronic Inflammation in Non-Healing Wounds

Macrophage Related Chronic Inflammation in Non-Healing Wounds

Wnt Glycation Inhibits Canonical Signaling

Elevated glycohemoglobin is linked to critical illness in COVID-19: a retrospective analysis

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