Cited by 24Advanced Glycation End Products researchNeuroinflammation and Neurodegeneration MechanismsAdipokines, Inflammation, and Metabolic Diseases

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?

Dhananjayan, Karthik, Gunawardena, Dhanushka, Hearn, Nerissa, Sonntag, Tanja, Moran, Chris, Gyengesi, Erika, Srikanth, Velandai, Münch, Gerald·2017·Journal of Alzheimer s Disease

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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Crossref · 10.3233/jad-161152

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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
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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