High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression
LUO Wei
WANG Yuhang
LIU Yansong
WANG Yuanyuan
AI Lei
Abstract：Objective 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-1 β 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-1βsecretion,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.Conclusion 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.
Keywords：macrophagesM1 polarizationinflammatory cytokineshigh glucose conditionimmune-responsive gene 1
Publication Date：2025-01-19
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：9( 1-9 )