scholarly journals Silver Nanoparticles Can Relieve Progressive Necrosis by Regulating Macrophage Activation in Burn Wounds

2021 ◽  
Author(s):  
Chuangang You ◽  
Shuangshuang Wang ◽  
Qiong Li ◽  
Songxue Guo ◽  
Abidullah Khan ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Macrophage Activation ◽  
Positive Influence ◽  
Histological Evaluation ◽  
M2 Macrophage ◽  
Burn Wound ◽  
M1 Macrophage ◽  
Progressive Necrosis ◽  
Very High ◽  
Made In

Abstract Purpose: To investigat the positive influence of AgNP on preventing early burn-wound progression.Patients and methods: After a deep burn, progression of burns may occur in the initial or surrounding area，even after thermal factors have been removed. Due to the influence of many factors such as residual heat, the risk of burn stagnant area deterioration is very high which is considered to be salvable. Silver nanoparticles (AgNP), which has been wide used in burns, is a strong antibacterial agent that has been reported to regulate inflammation. Hence, to investigat the positive influence of AgNP on avoid early burn wound progressive deterioration, a isomorphic “comb” burn animal model was made in this study which were treated with silver nanoparticles. The wound tissues were taken for molecular biological and histological evaluation, which revealed that AgNP alleviated histological deterioration in burn stagnant area. Results: Furthermore, AgNP can alleviate the early progressive necrosis and inflammatory response of burn wound, which was accociated with excitation in M2 macrophage and a suppression of M1 macrophage.Conclusion: In conclusion, we demonstrate that AgNP has a protective effect on acute burn wound deterioration in a rat model. It might be regulated by the macrophage activation-induced inflammation and apoptosis.

scholarly journals Macrophage activation in obese type 2 diabetes: an enhanced risk for COVID-19 and Acute Respiratory Distress Syndrome?

2020 ◽  
Author(s):  
Abu Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen Atkin ◽  
Alexandra Butler
Keyword(s):  
Type 2 Diabetes ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Serum Glucose ◽  
M2 Macrophage ◽  
Activation Markers ◽  
M1 Macrophage

Abstract Objective Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS), the hallmark of severe COVID-19 disease. Objectives: to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects.Methods A case-controlled interventional pilot study in OT2D (n=23) and control subjects (n=23). Subjects underwent hyperinsulinemic clamp normalizing serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-hour of insulin clamp (OT2D subjects only).Results. Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers CXCL9 and CXCL10 were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia.Conclusion In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences may predispose the diabetic individuals to ARDS reflecting in increased COVID-19 disease severity.

scholarly journals 1,25-Dihydroxyvitamin D3Promotes High Glucose-Induced M1 Macrophage Switching to M2 via the VDR-PPARγSignaling Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaoliang Zhang ◽  
Min Zhou ◽  
Yinfeng Guo ◽  
Zhixia Song ◽  
Bicheng Liu
Keyword(s):  
High Glucose ◽  
Macrophage Activation ◽  
M2 Macrophage ◽  
Activated Macrophages ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Raw264.7 Macrophages ◽  
M1 Macrophage ◽  
M1 Phenotype ◽  
Anti Inflammatory

Macrophages, especially their activation state, are closely related to the progression of diabetic nephropathy. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. 1,25-Dihydroxyvitamin D3has renoprotective roles that extend beyond the regulation of mineral metabolism, and PPARγ, a nuclear receptor, is essential for macrophage polarization. The present study investigates the effect of 1,25-dihydroxyvitamin D3on macrophage activation state and its underlying mechanism in RAW264.7 cells. We find that, under high glucose conditions, RAW264.7 macrophages tend to switch to the M1 phenotype, expressing higher iNOS and proinflammatory cytokines, including TNFαand IL-12. While 1,25-dihydroxyvitamin D3significantly inhibited M1 activation, it enhanced M2 macrophage activation; namely, it upregulated the expression of MR, Arg-1, and the anti-inflammatory cytokine IL-10 but downregulated the M1 markers. However, the above effects of 1,25-dihydroxyvitamin D3were abolished when the expression of VDR and PPARγwas inhibited by VDR siRNA and a PPARγantagonist. In addition, PPARγwas also decreased upon treatment with VDR siRNA. The above results demonstrate that active vitamin D promoted M1 phenotype switching to M2 via the VDR-PPARγpathway.

Macrophage Activation and M2 Polarization in Wound Bed of Diabetic Patients Treated by Dermal/Epidermal Substitute Nevelia

2020 ◽  
pp. 153473462094555 ◽  
Author(s):  
Manuela Montanaro ◽  
Marco Meloni ◽  
Lucia Anemona ◽  
Laura Giurato ◽  
Manuel Scimeca ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Macrophage Activation ◽  
Test Group ◽  
Inflammatory Cells ◽  
Foot Ulcers ◽  
Control Group ◽  
Diabetic Patients ◽  
M2 Macrophage ◽  
Diabetic Foot Ulcers ◽  
M1 Macrophage

Clinical evidences have shown good results using dermal/epidermal substitutes (DESs) to treat diabetic foot ulcers. Recent studies suggest that, in addition to their scaffold action, DESs may favor wound healing by influencing wound bed inflammatory cells. This study aims to investigate whether DES may influence the inflammatory infiltrate and macrophages polarization toward a reparative phenotype. Fifteen diabetic patients with chronic foot ulcers have been randomly enrolled: 5 treated only by standard of care, served as control group (CG), and 10 treated with DES composed of type 1 bovin collagen (Nevelia, SYMATESE) considered as test group (TG). A biopsy was taken at baseline (T0) and after 30 days (T1). From bioptic paraffin specimen histological, immunohistochemical, and immunofluorescence analysis was performed. Immunohistochemistry reactions evaluated the number of M1 macrophage (CD38+) and M2 macrophage (CD163+). TG patients displayed general macrophage activation and their greater polarization toward M2 subpopulation 30 days after DES implant, compared with CG. From T0 to T1 there was a significant decrease of CD38+ (230 ± 42 and 135 ± 48 mm2, respectively; P < .001) and significant increase of CD163+ (102 ± 21 positive cells/mm2 and 366 ± 42 positive cells/mm2, respectively; P < .001). Confocal microscopy confirmed an increase of M2 cells as expressed by the reduced CD68+/CD163+ ratio. After 6 months of observation 6 patients (60%) of the TG completely healed, while only 1 patient (20%) healed in the CG ( P < .01). The tested DES makes possible to treat diabetic foot ulcers inducing tissue reparative processes through macrophage activation and M2 reparative polarization.

scholarly journals Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Abu Saleh Md Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen L. Atkin ◽  
Alexandra E. Butler
Keyword(s):  
Type 2 Diabetes ◽  
Macrophage Activation ◽  
Serum Glucose ◽  
Surface Proteins ◽  
M2 Macrophage ◽  
Activation Markers ◽  
Obesity And Diabetes ◽  
M1 Macrophage ◽  
Glucose Plasma

AbstractHyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS. Clinical trial reg. no: NCT03102801; registration date April 6, 2017.

scholarly journals Distinct Redox Signalling following Macrophage Activation Influences Profibrotic Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Caitlin V. Lewis ◽  
Antony Vinh ◽  
Henry Diep ◽  
Chrishan S. Samuel ◽  
Grant R. Drummond ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Macrophage Activation ◽  
M2 Macrophage ◽  
Superoxide Generation ◽  
Amplex Red ◽  
Enhanced Chemiluminescence ◽  
M1 Macrophage ◽  
Adventitial Fibroblasts ◽  
Hydrogen Peroxide Generation ◽  
M1 And M2 Macrophages

Aims. To date, the ROS-generating capacities of macrophages in different activation states have not been thoroughly compared. This study is aimed at determining the nature and levels of ROS generated following stimulation with common activators of M1 and M2 macrophages and investigating the potential for this to impact fibrosis. Results. Human primary and THP-1 macrophages were treated with IFN-γ+LPS or IL-4-activating stimuli, and mRNA expression of established M1 (CXCL11, CCR7, IL-1β) and M2 (MRC-1, CCL18, CCL22) markers was used to confirm activation. Superoxide generation was assessed by L-012-enhanced chemiluminescence and was increased in both M(IFN-γ+LPS) and M(IL-4) macrophages, as compared to unpolarised macrophages (MΦ). This signal was attenuated with NOX2 siRNA. Increased expression of the p47phox and p67phox subunits of the NOX2 oxidase complex was evident in M(IFN-γ+LPS) and M(IL-4) macrophages, respectively. Amplex Red and DCF fluorescence assays detected increased hydrogen peroxide generation following stimulation with IL-4, but not IFN-γ+LPS. Coculture with human aortic adventitial fibroblasts revealed that M(IL-4), but not M(IFN-γ+LPS), enhanced fibroblast collagen 1 protein expression. Macrophage pretreatment with the hydrogen peroxide scavenger, PEG-catalase, attenuated this effect. Conclusion. We show that superoxide generation is not only enhanced with stimuli associated with M1 macrophage activation but also with the M2 stimulus IL-4. Macrophages activated with IL-4 also exhibited enhanced hydrogen peroxide generation which in turn increased aortic fibroblast collagen production. Thus, M2 macrophage-derived ROS is identified as a potentially important contributor to aortic fibrosis.

scholarly journals Saponin from Periploca forrestii Schltr Mitigates Oxazolone-Induced Atopic Dermatitis via Modulating Macrophage Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Luting Zeng ◽  
Yingqin Liu ◽  
Congcong Xing ◽  
Yijie Huang ◽  
Xin Sun ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Macrophage Activation ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Mouse Bone Marrow ◽  
Inflammatory Skin Diseases ◽  
M1 Macrophage

Atopic dermatitis (AD) is a relapsing, acute, and chronic skin disease featured by intractable itching, eczematous skin. Conventional therapies based on immunosuppression such as corticosteroids are associated with multiple adverse reactions. Periploca forrestii Schltr saponin (PFS) was shown to potently inhibit murine arthritis by protecting bone and cartilage injury and suppressing NF-κB activation. However, its therapeutic effect on oxazolone-induced atopic dermatitis (AD) and the underlying mechanisms on macrophage are still unclear. The AD-like dermatitis was induced by repeated oxazolone challenge to the skin of BALB/c mice in vivo. Blood and ears were biochemically or histologically processed. RT-PCR, western blotting, and ELISA were conducted to evaluate the expression of macrophage factors. Mouse bone marrow-derived macrophages (BMDMs) stimulated with lipopolysaccharide (LPS) were used as a model in vitro. PFS treatment inhibited AD-like dermatitis development. PFS downregulated epidermis thickness and cell infiltration, with histological analysis of the skin lesion. PFS alleviated plasma immunoglobulin (Ig) E, IgG2a, and IgG1 levels. PFS downregulated the expression of M1 macrophage factors, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, monocyte chemotactic protein-1 (MCP-1), and nitric oxide synthase2 (NOS2), and M2 macrophage factors, IL-4, arginase1 (Arg1) and CD163 in AD-like skin, which were confirmed by western blot and ELISA analysis. In addition, PFS inhibited LPS-induced macrophage polarization via the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and nuclear translocation of NF-κB p65. These results suggest that PFS exerted an antidermatitis effect against oxazolone by modulating macrophage activation. PFS administration might be useful in the treatment of AD and inflammatory skin diseases.

scholarly journals PAK1 Silencing Attenuated Proinflammatory Macrophage Activation and Foam Cell Formation by Increasing PPARγ Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Wen-Lin Cheng ◽  
Quan Zhang ◽  
Bo Li ◽  
Jian-Lei Cao ◽  
Lin Jiao ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Foam Cell ◽  
Macrophage Polarization ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
M2 Macrophage ◽  
Macrophage Phenotype ◽  
Loss Of Function ◽  
M1 Macrophage ◽  
Pparγ Expression

Macrophage polarization in response to environmental cues has emerged as an important event in the development of atherosclerosis. Compelling evidences suggest that P21-activated kinases 1 (PAK1) is involved in a wide variety of diseases. However, the potential role and mechanism of PAK1 in regulation of macrophage polarization remains to be elucidated. Here, we observed that PAK1 showed a dramatically increased expression in M1 macrophages but decreased expression in M2 macrophages by using a well-established in vitro model to study heterogeneity of macrophage polarization. Adenovirus-mediated loss-of-function approach demonstrated that PAK1 silencing induced an M2 macrophage phenotype-associated gene profiles but repressed the phenotypic markers related to M1 macrophage polarization. Additionally, dramatically decreased foam cell formation was found in PAK1 silencing-induced M2 macrophage activation which was accompanied with alternation of marker account for cholesterol efflux or influx from macrophage foam cells. Moderate results in lipid metabolism and foam cell formation were found in M1 macrophage activation mediated by AdshPAK1. Importantly, we presented mechanistic evidence that PAK1 knockdown promoted the expression of PPARγ, and the effect of macrophage activation regulated by PAK1 silencing was largely reversed when a PPARγ antagonist was utilized. Collectively, these findings reveal that PAK1 is an independent effector of macrophage polarization at least partially attributed to regulation of PPARγ expression, which suggested PAK1-PPARγ axis as a novel therapeutic strategy in atherosclerosis management.

scholarly journals Macrophage activation in obese type 2 diabetes: an enhanced risk for COVID-19 and Acute Respiratory Distress Syndrome?

2020 ◽  
Author(s):  
Abu Moin ◽  
Thozhukat Sathyapalan ◽  
Ilhame Diboun ◽  
Stephen Atkin ◽  
Alexandra Butler
Keyword(s):  
Type 2 Diabetes ◽  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Macrophage Activation ◽  
Distress Syndrome ◽  
Serum Glucose ◽  
M2 Macrophage ◽  
Activation Markers ◽  
M1 Macrophage

Abstract Objective Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS), the hallmark of severe COVID-19 disease. Objectives: to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects.Methods A case-controlled interventional pilot study in OT2D (n=23) and control subjects (n=23). Subjects underwent hyperinsulinemic clamp normalizing serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-hour of insulin clamp (OT2D subjects only).Results. Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers CXCL9 and CXCL10 were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia.Conclusion In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences may predispose the diabetic individuals to ARDS reflecting in increased COVID-19 disease severity.

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