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

Abstract

IntroductionMacrophages are central cells in mediating the inflammatory response.Objective and MethodsWe 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.ResultsWe 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.ConclusionThe results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.

M1-derived extracellular vesicles polarize recipient macrophages into M2-like macrophages and alter skeletal muscle homeostasis in a hyper-glucose environment

“…The effect of hyperglycemia on the differentiation and activation of subpopulations of macrophages has previously been investigated. It was found that HG-treatment on M1 macrophages pre-stimulated with LPS led to increased secretion of pro-inflammatory cytokines [ 20 , 53 ], associated with an increase in ROS production and autophagy in macrophages. An HG environment also induced the secretion of pro-inflammatory cytokines during the differentiation of primary human macrophages [ 54 ].…”

“…; diabetes) are associated with the development of low-grade inflammation and macrophage infiltration and polarization inside metabolic tissues [ 19 ]. Indeed, it was shown that under high-glucose (HG) conditions M1 macrophages exhibited an amplified pro-inflammatory response and had decreased production of anti-inflammatory mediators leading to sustained inflammation [ 20 ]. During diabetes onset and progression, hyperglycemia increased ROS production in macrophages, which favor induction of M1 pro-inflammatory macrophages [ 20 ].…”

“…Indeed, it was shown that under high-glucose (HG) conditions M1 macrophages exhibited an amplified pro-inflammatory response and had decreased production of anti-inflammatory mediators leading to sustained inflammation [ 20 ]. During diabetes onset and progression, hyperglycemia increased ROS production in macrophages, which favor induction of M1 pro-inflammatory macrophages [ 20 ]. Therefore, understanding the contribution of macrophages in chronic inflammation under HG concentrations is vital for developing targeted therapeutic strategies that can modulate macrophage function and mitigate the detrimental effects of hyperglycemia on inflammatory processes.…”

M1-derived extracellular vesicles polarize recipient macrophages into M2 and alter skeletal muscle homeostasis in a hyper-glucose environment

“…The effect of hyperglycemia on the differentiation and activation of subpopulations of macrophages has previously been investigated. It was found that HG-treatment on M1 macrophages pre-stimulated with LPS led to increased secretion of pro-inflammatory cytokines [46, 47], associated with an increase in ROS production and autophagy in macrophages. An HG environment also induced the secretion of pro-inflammatory cytokines during the differentiation of primary human macrophages [48].…”