Activation of Macrophages and Microglia by Interferon-γ and Lipopolysaccharide Increases Methylglyoxal Production: A New Mechanism in the Development of Vascular Complications and Cognitive Decline in Type 2 Diabetes Mellitus?
Abstract
Methylglyoxal (MGO), a dicarbonyl compound derived from glucose, is elevated in diabetes mellitus and contributes to vascular complications by crosslinking collagen and increasing arterial stiffness. It is known that MGO contributes to inflammation as it forms advanced glycation end products (AGEs), which activate macrophages via the receptor RAGE. The aim of study was to investigate whether inflammatory activation can increase MGO levels, thereby completing a vicious cycle. In order to validate this, macrophage (RAW264.7, J774A.1) and microglial (N11) cells were stimulated with IFN-γ and LPS (5 + 5 and 10 + 10 IFN-γ U/ml or μg/ml LPS), and extracellular MGO concentration was determined after derivatization with 5,6-Diamino-2,4-dihydroxypyrimidine sulfate by HPLC. MGO levels in activated macrophage cells (RAW264.7) peaked at 48 h, increasing 2.86-fold (3.14±0.4 μM) at 5 U/ml IFN-γ+5 μg/ml LPS, and 4.74-fold (5.46±0.30 μM) at 10 U/ml IFN-γ+10 μg/ml LPS compared to the non-activated controls (1.15±0.02 μM). The other two cell lines, J774A.1 macrophages and N11 microglia, showed a similar response. We suggest that inflammation increases MGO production, possibly exacerbating arterial stiffness, cardiovascular complications, and diabetes-related cognitive decline.
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- Authors
- Dhananjayan, K., Gunawardena, D., Hearn, N., Sonntag, T., Moran, C., Gyengesi, E., Srikanth, V., & Münch, G.
- Affiliations
- Western Sydney University (AU)
- Peninsula Health (AU)
- Department of Pharmacology, School of Medicine, Western Sydney University, Penrith, NSW, Australia
- Corresponding author
- Münch, Gerald
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2017-07-17
- Volume
- 59
- Issue
- 2
- Pages
- 467-479
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2617741929
- Cited by
- 24
- References
- 174
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 1
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- methylglyoxal, type 2 diabetes
- MeSH terms
- Analysis of Variance, Animals, Antiviral Agents, Cell Line, Transformed, Cell Survival, Dose-Response Relationship, Drug, Interferon-gamma, Lipopolysaccharides, Macrophages, Nitrites, Pyruvaldehyde, Time Factors, Microglia, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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