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High glucose increases RAW 264.7 macrophages activation by lipoteichoic acid from Staphylococcus aureus
Luiz Fernando de Souza1, Fernanda Rafaela Jardim, Ismael Pretto Sauter
1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 anexo, 90035-003 Porto Alegre, RS, Brazil. lzfsouza@yahoo.com.br
Background:
Type 2 diabetes mellitus is associated with an increased risk of cardiovascular diseases and accelerated atherosclerosis, which has been associated to hyperglycemia and chronic inflammation. Activated macrophages are described to participate in atherosclerosis due to foam cell formation and pro-inflammatory mediators production. Bacterial infections are described to accelerate atherosclerosis, moreover, gram-positive and negative bacterial DNA was described in atherosclerotic plaques.
Methods:
We studied the glucose modulation of RAW 264.7 macrophages activation by the gram-positive bacterial antigen lipoteichoic acid (LTA), evaluating nitrite production, tumor necrosis factor alpha secretion and matrix metalloproteinase 9 activity.
Results:
High glucose increased macrophages activation by LTA, evidenced by exacerbated nitric oxide and tumor necrosis factor alpha production, as well matrix metalloproteinase 9 secretion.
Conclusions:
These effects could contribute to atherosclerotic risk parameters, like atherome plaque instability, and participate in chronic inflammation present in type 2 diabetes.
Insights
High glucose exacerbates macrophage activation by bacterial components, increasing inflammation and potentially worsening atherosclerosis in type 2 diabetes patients.
Area of Science:
- Immunology
- Endocrinology
- Cardiovascular Research
Background:
- Type 2 diabetes mellitus (T2DM) is linked to cardiovascular disease and atherosclerosis, driven by hyperglycemia and chronic inflammation.
- Macrophages play a key role in atherosclerosis via foam cell formation and pro-inflammatory mediator release.
- Bacterial infections can accelerate atherosclerosis, with bacterial DNA found in plaques.
Purpose of the Study:
- To investigate how glucose levels modulate macrophage activation by bacterial antigens.
- To assess the impact of high glucose on macrophage inflammatory responses to lipoteichoic acid (LTA).
Main Methods:
- Utilized RAW 264.7 macrophages stimulated with lipoteichoic acid (LTA), a gram-positive bacterial antigen.
- Quantified nitrite production, tumor necrosis factor alpha (TNF-α) secretion, and matrix metalloproteinase 9 (MMP-9) activity under varying glucose conditions.
Main Results:
- High glucose significantly amplified LTA-induced macrophage activation.
- Exacerbated nitric oxide (NO) and TNF-α production were observed in high glucose conditions.
- Increased matrix metalloproteinase 9 (MMP-9) secretion was noted with high glucose and LTA stimulation.
Conclusions:
- Elevated glucose levels enhance bacterial antigen-driven macrophage activation.
- These findings suggest a mechanism contributing to atherosclerotic plaque instability and chronic inflammation in T2DM.
- The results highlight the interplay between hyperglycemia, bacterial components, and macrophage-mediated inflammation in diabetes-related cardiovascular risk.
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