Epigenetic modulation of macrophage polarization- perspectives in diabetic wounds

Mallik, Sanchari Basu; Jayashree, B. S.; Shenoy, Rekha R

doi:10.1016/j.jdiacomp.2018.01.015

Cited by 69 publications

(55 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The process of wound healing is also associated with the plasticity of monocytes, as they are involved in homeostasis and tissue remodeling [30], since the regenerative potential is associated with monocyte secretion of anti-inflammatory cytokines and growth factors that stimulate the proliferation of fibroblasts. Dysregulation of activation of monocytes is one of the main reasons for delayed wound healing [31,32]. We studied the activation of blood-derived monocytes in patients with different wound healing durations.…”

Section: Discussionmentioning

confidence: 99%

Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

Galstyan

Недосугова

Мартиросян

et al. 2019

Biology

View full text Add to dashboard Cite

Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. Methods: A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-α (r = 0.726, p = 0.027) and CCL18 (r = –0.949, p = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (p = 0.033). Conclusions: Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.

show abstract

Section: Discussionmentioning

confidence: 99%

Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

Galstyan

Недосугова

Мартиросян

et al. 2019

Biology

View full text Add to dashboard Cite

show abstract

“…The effects of the glycolipid metabolic disorder on the macrophage phenotypic change may be distinct in different tissues. Macrophages exposed to the diabetic environment are also preferentially polarized toward M1, contributing to multiple pathologies in the target organs . M1 cells are the main macrophages in the adipose tissue of obese people .…”

Section: M2b Macrophages and Diseasesmentioning

confidence: 99%

“…Macrophages exposed to the diabetic environment are also preferentially polarized toward M1, contributing to multiple pathologies in the target organs. 154 M1 cells are the main macrophages in the adipose tissue of obese people. 153 Additionally, macrophages in the peritoneal cavity and the cecal tissue from high-fat fed mice present M2b polarization (IL-10 + , TNF-+ , MR + , Dectin-1 + ) at the site of infection that is associated with an increased susceptibility to gastrointestinal candidiasis.…”

Section: M2b Macrophages In Glycolipid Metabolic Disordersmentioning

confidence: 99%

M2b macrophage polarization and its roles in diseases

Wang

Zhang

et al. 2018

Journal of Leukocyte Biology

622

455

View full text Add to dashboard Cite

Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune‐regulated and anti‐inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization.

show abstract

“…Hypothetically, higher IRF4 expression level in differentiated macrophages from our study may be interpreted as a kind of compensatory immune mechanism generated under inflammatory state, to keep a balance between anti-and proinflammatory responses, but it is hard to speculate which condition leads to the IRF4 and IRF5 overexpression in DM1 patients. However, the epigenetic modification in gene expression may contribute to dysregulation of macrophage polarisation status [54]. For example, upregulation of the Irf4 may be induced by Jmjd3 via demethylation of H3K27 in normal condition [55], but it may be disturbed by hyperglycaemia.…”

Section: Discussionmentioning

confidence: 99%

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

et al. 2019

View full text Add to dashboard Cite

Alternatively activated macrophages (M2) exert anti-inflammatory effects and are crucial for keeping balance between protective and destructive cell-mediated immunity in healing phase of inflammation. Two members of the interferon regulatory factors family, IRF5 and IRF4, are known to promote M1 or M2 phenotype, respectively. Our study aimed to analyse the effectiveness of the M2 differentiation process in vitro (achieved by IL-4 stimulation) and its relationship to the stage of type 1 diabetes mellitus (DM1) in juvenile patients. To identify the basic changes in M2 phenotype, we examined the expression of the surface CD206, CD14, CD86 molecules, intracellular IRF4 and IRF5 transcription factors as well as IL-10 and TNFα intracellular production. Ten newly diagnosed (ND-DM1) and ten long-standing (LS-DM1) patients were enrolled into the study. The control group consisted of six children. We observed a significantly higher number of unpolarised CD206 + CD14 + cells in the M2 cultures of DM1 subjects when compared to healthy ones. Examined cells presented common features with M1 macrophages (high levels of the CD14/CD86/IRF5 markers); however, they were weak TNFα producers in ND-DM1 patients. For the first time, we have revealed dysregulated IRF4/IRF5 axis in the analysed subpopulation derived from diabetic patients. Additionally, monocytes of ND-DM1 children were still able to differentiate into regulatory IL-10 + M2 macrophages, while this process was highly limited in LS-DM1 patients. Summarising, we suggest that the M2 polarisation process is less effective in DM1 patients than in healthy subjects and it may vary depending on the stage of disease. It can be concluded that in vitro differentiated M2 macrophages may be used in the future as inflammatory inhibitors for adoptive therapy experiments in ND-DM1 subjects.

show abstract

Epigenetic modulation of macrophage polarization- perspectives in diabetic wounds

Cited by 69 publications

References 85 publications

Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

Modification of Tumor Necrosis Factor-α and C-C Motif Chemokine Ligand 18 Secretion by Monocytes Derived from Patients with Diabetic Foot Syndrome

M2b macrophage polarization and its roles in diseases

Monocytes of newly diagnosed juvenile DM1 patients are prone to differentiate into regulatory IL-10+ M2 macrophages

Contact Info

Product

Resources

About