The influence of high glucose conditions on macrophages and its effect on the autophagy pathway

Macrophages are central cells in mediating the inflammatory response. We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6...

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Published in:Frontiers in immunology 2023-04, Vol.14, p.1130662-1130662
Main Authors: Sousa, Emanuella S A, Queiroz, Luiz A D, Guimarães, João P T, Pantoja, Kamilla C, Barros, Rafael S, Epiphanio, Sabrina, Martins, Joilson O
Format: Article
Language:English
Subjects:
Animals
Autophagy
Beclin-1 - metabolism
Cytokines - metabolism
diabetes mellitus
Glucose - metabolism
hyperglycemia
Immunology
inflammation
Interleukin-6 - metabolism
Lipopolysaccharides - pharmacology
macrophages
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Nigericin - pharmacology
Tumor Necrosis Factor-alpha - metabolism
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Summary:Macrophages are central cells in mediating the inflammatory response. We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6 mice. BMDM were cultured in medium with normal glucose (5.5 mM), or high glucose (25 mM) concentration and were primed with Nigericin (20µM) stimulated with LPS (100 ng/mL) at times of 30 minutes; 2; 4; 6 and 24 hours, with the measurement of IL-6, IL-1β and TNF-α cytokines. We have further identified changes in the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α, where BMDM showed increased secretion of these cytokines after LPS + Nigericin stimulation. In addition, changes were observed in the autophagy pathway, where the increase in the autophagic protein LC3b and Beclin-1 occurred by macrophages of non-diabetic animals in hyperglycemic medium, without LPS stimulation. D-BMDM showed a reduction on the expression of LC3b and Beclin-1, suggesting an impaired autophagic process in these cells. The results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1130662