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

Front Immunol. 2023 Apr 12:14:1130662. doi: 10.3389/fimmu.2023.1130662. eCollection 2023.

Abstract

Introduction: Macrophages are central cells in mediating the inflammatory response.

Objective and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: autophagy; diabetes mellitus; hyperglycemia; inflammation; macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Beclin-1 / metabolism
  • Cytokines / metabolism
  • Glucose / metabolism
  • Interleukin-6* / metabolism
  • Lipopolysaccharides / pharmacology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nigericin / pharmacology
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Lipopolysaccharides
  • Beclin-1
  • Nigericin
  • Cytokines
  • Glucose

Grants and funding

The authors are supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP: 2017/11540-7; 2020/13215-9; 2020/03163-1, 2022/00482-4 and 2023/02989-1); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq: 310993/2020-2 and 304033/2021-9), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 88882.327675/2019-01).