M1/M2 macrophages and their overlaps – myth or reality?

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1067 - 1093

Published: Aug. 1, 2023

Abstract Macrophages represent heterogeneous cell population with important roles in defence mechanisms and homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 M2 are two polarized forms of mononuclear phagocyte vitro differentiation phenotypic patterns functional properties, but vivo, there is a wide range different macrophage phenotypes between depending on the microenvironment natural signals they receive. In human infections, pathogens use strategies to combat these include shaping polarization towards one or another phenotype. infiltrating tumours can affect patient’s prognosis. have been shown promote tumour growth, while provide both tumour-promoting anti-tumour properties. autoimmune diseases, prolonged activation, as well altered function contribute their onset activity. atherosclerotic lesions, expressing profiles detected potential factors affecting occurrence cardiovascular diseases. allergic inflammation, T2 cytokines drive profiles, which airway inflammation remodelling. transplantations seem acute rejection, fibrosis graft. The view pro-inflammatory suppressing seems be an oversimplification because cells exploit very high level plasticity large scale immunophenotypes overlapping this respect, it would more precise describe M1-like M2-like.

Language: Английский

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Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: Aug. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Language: Английский

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Function and inhibition of P38 MAP kinase signaling: Targeting multiple inflammation diseases

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 220, P. 115973 - 115973

Published: Dec. 14, 2023

Language: Английский

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Enhancer of zeste homolog 2 promotes renal fibrosis after acute kidney injury by inducing epithelial-mesenchymal transition and activation of M2 macrophage polarization

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 7, 2023

Abstract Long-term follow-up data indicates that 1/4 patients with acute kidney injury (AKI) will develop to chronic disease (CKD). Our previous studies have demonstrated enhancer of zeste homolog 2 (EZH2) played an important role in AKI and CKD. However, the mechanisms EZH2 AKI-to-CKD transition are still unclear. Here, we H3K27me3 highly upregulated from ANCA-associated glomerulonephritis, expressed positively fibrotic lesion negatively renal function. Conditional deletion or pharmacological inhibition 3-DZNeP significantly improved function attenuated pathological ischemia/reperfusion (I/R) folic acid (FA) mice models (two transition). Mechanistically, used CUT & Tag technology verify binding PTEN promoter regulating its transcription, thus downstream signaling pathways. Genetic depletion expression suppressed phosphorylation EGFR ERK1/2 STAT3, consequently alleviating partial epithelial-mesenchymal (EMT), G2/M arrest, aberrant secretion profibrogenic proinflammatory factors vivo vitro experiments. In addition, promoted EMT program induced loss tubular epithelial cell transporters (OAT1, ATPase, AQP1), blockade prevented it. We further co-cultured macrophages medium human cells treated H O found transferred M2 phenotype, could regulate macrophage polarization through STAT6 PI3K/AKT These results were verified two models. Thus, targeted might be a novel therapy for ameliorating fibrosis after by counteracting polarization.

Language: Английский

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6-Gingerol microneedle promotes diabetic wound healing by regulating macrophage polarization

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 151, P. 114288 - 114288

Published: Feb. 24, 2025

Language: Английский

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Plant‐derived exosomes extracted from Lycium barbarum L. loaded with isoliquiritigenin to promote spinal cord injury repair based on 3D printed bionic scaffold

Bioengineering & Translational Medicine, Journal Year: 2024, Volume and Issue: 9(4)

Published: Jan. 30, 2024

Abstract Plant‐derived exosomes (PEs) possess an array of therapeutic properties, including antitumor, antiviral, and anti‐inflammatory capabilities. They are also implicated in defensive responses to pathogenic attacks. Spinal cord injuries (SCIs) regeneration represents a global medical challenge, with appropriate research concentration on three pivotal domains: neural promotion, inflammation inhibition, innovation application regenerative scaffolds. Unfortunately, the utilization PE SCI therapy remains unexplored. Herein, we isolated from traditional Chinese medicinal herb, Lycium barbarum L. discovered their inflammatory inhibition neuronal differentiation promotion Compared derived ectomesenchymal stem cells (EMSCs), demonstrated substantial enhancement differentiation. We encapsulated isoliquiritigenin (ISL)‐loaded plant‐derived (ISL@PE) within 3D‐printed bionic scaffold. The intricate construct modulated response following SCI, facilitating restoration damaged axons culminating ameliorated neurological function. This pioneering investigation proposes novel potential route for insoluble drug delivery via plant exosomes, as well repair. institutional animal care use committee number is UJS‐IACUC‐2020121602.

Language: Английский

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Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 375, P. 300 - 315

Published: Sept. 17, 2024

Language: Английский

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α-Aminobutyric Acid Constrains Macrophage-Associated Inflammatory Diseases through Metabolic Reprogramming and Epigenetic Modification

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(13), P. 10444 - 10444

Published: June 21, 2023

Metabolites play critical roles in macrophage polarization and their function response to infection inflammation. α-aminobutyric acid (AABA), a non-proteinogenic amino which can be generated from methionine, threonine, serine, glycine, has not been studied extensively relation function. In this study, we aimed investigate the immunomodulatory of AABA regulating M1 vitro vivo. We stimulated bone-marrow-derived macrophages with lipopolysaccharide (LPS) generate macrophages. Subsequently, induced sepsis colitis mice, followed by treatment AABA. then analyzed samples using ELISA, real-time PCR, Western blotting, flow cytometry, histopathological analysis evaluate cytokine secretion, inflammatory gene expression, activation, disease progression, inflammation severity. Additionally, metabolomic chromatin immunoprecipitation-qPCR were conducted on metabolic reprogramming epigenetic modifications Our results revealed that inhibited function, led prolonged survival septic mice reduced severity mice. Mechanically, promoted oxidative phosphorylation (OXPHOS) glutamine arginine metabolism while inhibiting glycolysis. Moreover, could increase occupancy trimethylation histone H3K27 at promoter regions macrophage-associated genes, contributed inhibition polarization. These findings suggest may have therapeutic potential for diseases through pathways.

Language: Английский

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Thermoresponsive M1 macrophage-derived hybrid nanovesicles for improved in vivo tumor targeting

Drug Delivery and Translational Research, Journal Year: 2023, Volume and Issue: 13(12), P. 3154 - 3168

Published: June 26, 2023

Despite the efforts and advances done in last few decades, cancer still remains one of main leading causes death worldwide. Nanomedicine particular extracellular vesicles are most potent tools to improve effectiveness anticancer therapies. In these attempts, aim this work is realize a hybrid nanosystem through fusion between M1 macrophages-derived (EVs-M1) thermoresponsive liposomes, order obtain drug delivery system able exploit intrinsic tumor targeting capability immune cells reflected on EVs thermoresponsiveness synthetic nanovesicles. The obtained nanocarrier has been physicochemically characterized, hybridization process validated by cytofluorimetric analysis, while was vitro confirmed use fluorescent probe. Tumor features nanovesicles were vivo investigated melanoma-induced mice model monitoring accumulation site live imaging showing higher properties compared both liposomes native EVs. These promising results ability combine advantages nanotechnologies, also highlighting their potential as effective safe personalized nanomedicine.

Language: Английский

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Smart Hydrogel Dressing Enhances the Healing of Chronic Infectious Diabetic Wounds through Dual-Barrier Drug Delivery Action

Biomacromolecules, Journal Year: 2024, Volume and Issue: 25(10), P. 6814 - 6829

Published: Sept. 5, 2024

Chronic diabetic wounds struggle to heal due drug-resistant bacterial infections, oxidative stress microenvironment, and immune dysfunction. At present, the disease has become a huge clinical challenge. Multifunctional hydrogels with antibacterial, antioxidant, anti-inflammatory properties are becoming an emerging trend in treatment of chronic wounds. However, matching different bioactive functions wound healing process sequentially exert anti-inflammatory, immunomodulatory remains significant In this research, hydrogel dressing bactericidal was synthesized by crafting pH/ROS-responsive scaffold from phenylboronic acid-grafted hyaluronic acid (HA-PBA) 4-arm-PEG-dopamine (4A-PEG-Dopa), employing dynamic borate ester bonds. This structure then infused antimicrobial peptide (AMP) ROS-sensitive micelle mPEG-TK-PLGA loaded quercetin (QC). embodied dual-barrier drug delivery mechanism, engineered for prolonged consistent liberation QC. experiment, dissociated within acidic microenvironment wounds, thereby liberating encapsulated micelles AMP. Upon further dissociation, release QC ROS-abundant which could relieve encourage M2 polarization macrophage via Akt/STAT6 signaling pathway. Therefore, smart system, developed through our innovative approach, holds promise treating infectious

Language: Английский

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