High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression.
10.12122/j.issn.1673-4254.2025.01.01
- Author:
Wei LUO
1
;
Yuhang WANG
1
;
Yansong LIU
1
;
Yuanyuan WANG
1
;
Lei AI
2
Author Information
1. School of Sport and Health, Nanjing Sport Institute, Nanjing 210014, China.
2. Jiangsu Research Institute of Sports Science, Nanjing 210033, China.
- Publication Type:Journal Article
- Keywords:
M1 polarization;
high glucose condition;
immune-responsive gene 1;
inflammatory cytokines;
macrophages
- MeSH:
Animals;
Mice;
Macrophages/drug effects*;
Glucose/pharmacology*;
Interleukin-10/metabolism*;
Nitric Oxide Synthase Type II/metabolism*;
RAW 264.7 Cells;
Interleukin-1beta/metabolism*;
Arginase/metabolism*;
RNA, Small Interfering/genetics*;
Transfection;
Inflammation
- From:
Journal of Southern Medical University
2025;45(1):1-9
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect.
METHODS:RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy. The protein levels of IRG1, iNOS, Arg-1, IL-1β and IL-10 in the treated cells were detected with Western blotting, and the fluorescence intensities of iNOS and Arg-1 were detected using immunofluorescence assay. The protein levels of IL-1β and IL-10 in the culture medium were determined with ELISA.
RESULTS:High glucose exposure significantly reduced IRG1 and Arg-1 expressions, increased iNOS and IL-1β expressions and IL-1β secretion, and decreased IL-10 level in RAW264.7 cells. Transfection with the IRG1-overexpressing plasmid provided the cells with obvious resistance to high glucose-induced changes in iNOS, Arg-1, IL-1β and IL-10, whereas IRG1 knockdown further enhanced the effects of high glucose exposure on Arg-1 expression and the expression and secretion of IL-10.
CONCLUSIONS:High glucose promotes M1 polarization of the macrophages possibly through a mechanism to inhibit the expression of IRG1 protein, thus leading to chronic inflammatory response.
