scholarly journals Macrophage Differentiation from Monocytes Is Influenced by the Lipid Oxidation Degree of Low Density Lipoprotein

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Won Seo ◽  
Eun-Jeong Yang ◽  
Kyung-Hwa Yoo ◽  
In-Hong Choi
Keyword(s):  
Lipid Oxidation ◽  
Oxidized Ldl ◽  
Mannose Receptor ◽  
Receptor Expression ◽  
Supporting Evidence ◽  
M2 Macrophages ◽  
Macrophage Phenotype ◽  
Macrophage Differentiation ◽  
Oxidation Degree ◽  
M1 Macrophage

LDL plays an important role in atherosclerotic plaque formation and macrophage differentiation. However, there is no report regarding the oxidation degree of LDL and macrophage differentiation. Our study has shown that the differentiation into M1 or M2 macrophages is related to the lipid oxidation level of LDL. Based on the level of lipid peroxidation, LDL is classified into high-oxidized LDL (hi-oxLDL) and low-oxidized LDL (low-oxLDL). The differentiation profiles of macrophages were determined by surface receptor expression and cytokine secretion profiles. Low-oxLDL induced CD86 expression and production of TNF-αand IL-12p40 in THP-1 cells, indicating an M1 macrophage phenotype. Hi-oxLDL induced mannose receptor expression and production of IL-6 and monocyte chemoattractant protein-1, which mostly match the phenotype of M2 macrophages. Further supporting evidence for an M2 polarization by hi-oxLDL was the induction of LOX-1 in THP-1 cells treated with hi-oxLDL but not with low-oxLDL. Similar results were obtained in primary human monocytes. Therefore, our results strongly suggest that the oxidation degree of LDL influences the differentiation of monocytes into M1 or M2 macrophages and determines the inflammatory fate in early stages of atherosclerosis.

scholarly journals Oxidized LDL Induces Alternative Macrophage Phenotype through Activation of CD36 and PAFR

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Francisco J. Rios ◽  
Marianna M. Koga ◽  
Mateus Pecenin ◽  
Matheus Ferracini ◽  
Magnus Gidlund ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Macrophage Activation ◽  
Oxidized Ldl ◽  
Platelet Activating Factor ◽  
Mannose Receptor ◽  
Mrna Levels ◽  
Macrophage Phenotype ◽  
Macrophage Differentiation ◽  
Arginase 1 ◽  
Pre Treatment

OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR) is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARγand arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-βsignificantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-β, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV) or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR.

Abstract 94: Deficiency of Epsins in Macrophages Ameliorates Atherosclerosis by Attenuating Inflammation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Megan L Brophy ◽  
Yunzhou Dong ◽  
Hao Wu ◽  
Kai Song ◽  
Ashiqur Rahman ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Cell ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

Background: Atherosclerosis is caused by the immune and inflammatory cell infiltration of the vascular wall, leading to enhanced inflammation and lipid accumulation. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Our recently studies demonstrate that endothelial epsins, a family of ubiquitin-binding endocytic adaptors are critical regulators of atherosclerosis. However, whether epsins in macrophages play a role in regulating vascular inflammation is unknown. We hypothesize that epsins in macrophages promote inflammation to facilitate atherogenesis. Methods and Results: We engineered myeloid cell-specific epsins double knockout mice (MΦ-DKO) on an ApoE-/- background fed western diet. Strikingly, these mice exhibited reduced atherosclerotic lesion formation, diminished immune and inflammatory cell recruitment to aortas and reduced cleaved caspase 3 staining but increased α-SMA staining within aortic root sections. Epsin deficiency hindered foam cell formation, suppressed the pro-inflammatory M1 macrophage phenotype but increased the anti-inflammatory macrophage phenotype, and enhanced efferocytosis in primary macrophages. Mechanistically, we show that epsin loss specifically increases total and surface levels of LRP-1, a protein with anti-inflammatory properties without altering levels of LDL scavenger receptors. We further show that epsin and LRP-1 interact via epsin’s UIM domain. Oxidized LDL treatment increased LRP-1 ubiquitination and subsequent binding to epsin while mutation of cytoplasmic lysine residues attenuated LRP-1 ubiquitination, suggesting that epsin promotes the ubiquitin-dependent internalization and degradation of LRP-1. Importantly, MΦ-DKO/ApoE null mice on LRP-1 heterozygous background restored atherosclerosis, suggesting that epsin-mediated LRP-1 downregulation in macrophages plays a pivotal role in propelling atherogenesis. Conclusions: Macrophage epsins promote atherogenesis, in part, by facilitating pro-inflammatory macrophage recruitment and potentiating foam cell formation by downregulating LRP-1, implicating that targeting epsin in macrophages may serve as a novel therapeutic strategy to treat atheroma.

scholarly journals IRF5 Is a Specific Marker of Inflammatory MacrophagesIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Miriam Weiss ◽  
Katrina Blazek ◽  
Adam J. Byrne ◽  
Dany P. Perocheau ◽  
Irina A. Udalova
Keyword(s):  
Specific Marker ◽  
M2 Macrophages ◽  
Macrophage Phenotype ◽  
Tissue Remodelling ◽  
Murine Bone Marrow ◽  
Macrophage Polarisation ◽  
M1 Macrophage ◽  
Anti Inflammatory

Macrophages are an integral part of the innate immune system and key players in pathogen clearance and tissue remodelling. Both functions are accomplished by a pivotal network of different macrophage subtypes, including proinflammatory M1 and anti-inflammatory M2 macrophages. Previously, our laboratory identified the transcription factor interferon regulatory factor 5 (IRF5) as the master regulator of the M1 macrophage polarisation. IRF5 was found to be highly expressed in human M1 compared to M2 macrophages. Furthermore, IRF5 dictates the expression of proinflammatory genes such asIL12bandIL23awhilst repressing anti-inflammatory genes likeIL10. Here we show that murine bone marrow derived macrophages differentiatedin vitrowith GM-CSF are also characterised by high levels of IRF5 mRNA and protein and express proinflammatory cytokines upon LPS stimulation. These macrophages display characteristic expression of M1-marker MHC II but lack the M2-marker CD206. Significantly, we develop intracellular staining of IRF5- expressing macrophages and utilise it to recapitulate thein vitroresults in anin vivomodel of antigen-induced arthritis, emphasising their physiological relevance. Thus, we establish the species-invariant role of IRF5 in controlling the inflammatory macrophage phenotype bothin vitroand inin vivo.

Reprogrammed M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 extends lifespan of mice with experimental carcinoma

2017 ◽  
pp. 4-9
Author(s):  
С.В. Калиш ◽  
С.В. Лямина ◽  
А.А. Раецкая ◽  
И.Ю. Малышев
Keyword(s):  
Tumor Growth ◽  
Culture Medium ◽  
Ehrlich Carcinoma ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Ec Cells ◽  
Experimental Carcinoma

Цель исследования. Репрограммирование М1 фенотипа макрофагов с ингибированными факторами транскрипции М2 фенотипа STAT3, STAТ6 и SMAD и оценка их влияния на развитие карциномы Эрлиха (КЭ) in vitro и in vivo. Методика. Рост опухоли иницировали in vitro путем добавления клеток КЭ в среду культивирования RPMI-1640 и in vivo путем внутрибрюшинной инъекции клеток КЭ мышам. Результаты. Установлено, что M1макрофаги и in vitro, и in vivo оказывают выраженный противоопухолевый эффект, который превосходит антиопухолевые эффекты М1, M1, M1 макрофагов и цисплатина. Заключение. М1 макрофаги с ингибированными STAT3, STAT6 и/или SMAD3 эффективно ограничивают рост опухоли. Полученные данные обосновывают разработку новой технологии противоопухолевой клеточной терапии. Objective. Reprogramming of M1 macrophage phenotype with inhibited M2 phenotype transcription factors, such as STAT3, STAT6 and SMAD and assess their impact on the development of Ehrlich carcinoma (EC) in vitro and in vivo . Methods. Tumor growth in vitro was initiated by addition of EC cells in RPMI-1640 culture medium and in vivo by intraperitoneal of EC cell injection into mice. Results. It was found that M1 macrophages have a pronounced anti-tumor effect in vitro , and in vivo , which was greater than anti-tumor effects of M1, M1, M1 macrophages and cisplatin. Conclusion. M1 macrophages with inhibited STAT3, STAT6 and/or SMAD3 effectively restrict tumor growth. The findings justify the development of new anti-tumor cell therapy technology.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

Abstract 190: Epigenetic Modifications of Pro-inflammatory Gene Expression in Macrophages by a Demethylase Enzyme, JMJD3, May Promote Chronic Inflammation in Type 2 Diabetic (T2D) Wounds

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Katherine A Gallagher ◽  
Amrita Joshi ◽  
William Carson ◽  
Dawn Coleman ◽  
Peter Henke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Chronic Inflammation ◽  
Histone Methylation ◽  
Gene Promoter ◽  
Epigenetic Modifications ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Type 2 Diabetic

Introduction Type 2 diabetic(T2D) wounds are characterized by chronic inflammation, maintained by an exaggerated M1(pro-inflammatory) macrophage phenotype response. We seek to define a link between epigenetic modifications of bone marrow(BM) cells in T2D and dysregulated macrophages in wounds. We hypothesized that a chromatin modifying demethylase enzyme, JMJD3, is responsible for the decrease in H3K27me3 repressive methylation at the IL-12 gene promoter and thus drives an M1 macrophage phenotype in T2D wounds. Methods BM/adipose tissue(AT)/wounds were harvested from 30 diet-induced obese mice(DIO)(MG= 350g/DL) and 30 matched(WT) controls. For chromatin immunoprecipitation(ChIP) analysis, cells were isolated via ferromagnetic columns(CD34+,CD11b+). ChIP to detect histone methylation at the promoter regions of JMJD3 and IL-12(key M1 macrophage gene) was performed and RNA analysis was done with standard primers. Results JMJD3 mRNA in the BM is significantly increased in the DIO versus WT. ChIP showed increased H3K4me3(gene expression mark) in CD34+ progenitor cells and a corresponding decrease in H3K27me3(repressive mark) in monocytes at the promoter region of JMJD3. These changes correspond with the decrease in H3K27me3 seen at the IL-12 promoter in macrophages(CD11b+) from AT/T2D wounds. Conclusions Epigenetic changes initiated by JMJD3 in BM progenitor cells result in changes in histone methylation at the IL-12 promoter favoring an M1 phenotype in macrophages and thus contributes to the chronic inflammation seen in T2D wounds and AT. Whether manipulation of epigenetic enzymes could reduce chronic inflammation in T2D wounds requires further work.

scholarly journals The Role of Toll-Like Receptors in the Production of Cytokines by Human Lung Macrophages

2018 ◽  
Vol 12 (1) ◽  
pp. 63-73 ◽  
Author(s):  
Stanislas Grassin-Delyle ◽  
Charlotte Abrial ◽  
Hélène Salvator ◽  
Marion Brollo ◽  
Emmanuel Naline ◽  
...  
Keyword(s):  
Human Lung ◽  
Macrophage Phenotype ◽  
Chemokine Production ◽  
Lung Macrophages ◽  
Cytokines And Chemokines ◽  
M1 Macrophage ◽  
Microbial Infections ◽  
Selective Agonists ◽  
And Function ◽  
Subtype Selective

Background: The Toll-like receptor (TLR) family is involved in the recognition of and response to microbial infections. These receptors are expressed in leukocytes. TLR stimulation induces the production of proinflammatory cytokines and chemokines. Given that human lung macrophages (LMs) constitute the first line of defense against inhaled pathogens, the objective of this study was to investigate the expression and function of TLR subtypes in this cell population. Methods: Human primary LMs were obtained from patients undergoing surgical resection. The RNA and protein expression levels of TLRs, chemokines, and cytokines were assessed after incubation with subtype-selective agonists. Results: In human LMs, the TLR expression level varied from one subtype to another. Stimulation with subtype-selective agonists induced an intense, concentration- and time-dependent increase in the production of chemokines and cytokines. TLR4 stimulation induced the strongest effect, whereas TLR9 stimulation induced a much weaker response. Conclusions: The stimulation of TLRs in human LMs induces intense cytokine and chemokine production, a characteristic of the proinflammatory M1 macrophage phenotype.

scholarly journals Acid Sphingomyelinase Controls Early Phases of Skeletal Muscle Regeneration by Shaping the Macrophage Phenotype

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3028
Author(s):  
Paulina Roux-Biejat ◽  
Marco Coazzoli ◽  
Pasquale Marrazzo ◽  
Silvia Zecchini ◽  
Ilaria Di Renzo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Acid Sphingomyelinase ◽  
Skeletal Muscle Regeneration ◽  
Sphingolipid Metabolism ◽  
M2 Macrophages ◽  
Macrophage Phenotype ◽  
M1 Macrophages ◽  
Early Phases

Skeletal muscle regeneration is a complex process involving crosstalk between immune cells and myogenic precursor cells, i.e., satellite cells. In this scenario, macrophage recruitment in damaged muscles is a mandatory step for tissue repair since pro-inflammatory M1 macrophages promote the activation of satellite cells, stimulating their proliferation and then, after switching into anti-inflammatory M2 macrophages, they prompt satellite cells’ differentiation into myotubes and resolve inflammation. Here, we show that acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, is activated after skeletal muscle injury induced in vivo by the injection of cardiotoxin. ASMase ablation shortens the early phases of skeletal muscle regeneration without affecting satellite cell behavior. Of interest, ASMase regulates the balance between M1 and M2 macrophages in the injured muscles so that the absence of the enzyme reduces inflammation. The analysis of macrophage populations indicates that these events depend on the altered polarization of M1 macrophages towards an M2 phenotype. Our results unravel a novel role of ASMase in regulating immune response during muscle regeneration/repair and suggest ASMase as a supplemental therapeutic target in conditions of redundant inflammation that impairs muscle recovery.

scholarly journals Experimental Trichinellosis in rats: Peritoneal macrophage activity

2010 ◽  
Vol 62 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Alisa Gruden-Movsesijan ◽  
Ljiljana Sofronic-Milosavljevic
Keyword(s):  
Immune Status ◽  
Trichinella Spiralis ◽  
Mannose Receptor ◽  
Peritoneal Macrophages ◽  
Receptor Expression ◽  
No Production ◽  
Parasitic Disease ◽  
Macrophage Activity ◽  
Life Cycle Stages ◽  
Dynamic Shift

The influence of Trichinella spiralis infection on macrophage activity in rats during the first 28 days of infection was examined by measuring the production of NO and IL-6, as well as the expression of mannose receptor on the surface of peritoneal macrophages. During the course of a dynamic shift in the 3 life-cycle stages of the parasite, intermittent variations in NO production were observed but ended with increased values that coincided with the highest values for IL-6 release in the final, muscle phase of infection. No change in mannose receptor expression was observed during the course of infection. These results confirm that the Trichinella spiralis infection provokes changes in macrophage activity that could influence not only the course of the parasitic disease but also the overall immune status of the host.

scholarly journals Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 938
Author(s):  
Yi-Hsuan Lin ◽  
Yi-Hsun Wang ◽  
Yi-Jen Peng ◽  
Feng-Cheng Liu ◽  
Gu-Jiun Lin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Macrophage Polarization ◽  
Enzyme Linked Immunosorbent Assay ◽  
M2 Macrophage ◽  
Macrophage Differentiation ◽  
Macrophage Cells ◽  
M1 Macrophage ◽  
Interleukin 26

Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Human or mouse macrophage cells were treated with lipopolysaccharides (LPS), interferon gamma (IFNγ), or IL-4 alone or concurrently treated with IL-26 to monitor M1 or M2 macrophage subtypes. The expression level of M1 or M2 macrophage genes was evaluated by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanisms of downstream signaling activation during differentiation were investigated by immunoblotting assay. Our results found that IL-26 promoted macrophage cells from CD80+ M1 macrophage differentiation, not from the CD206+ M2 phenotype. The messenger RNA of M1-type macrophage markers tumor necrosis factor alpha (TNFα) and inducible nitric oxide synthase (iNOS) was up-regulated in the IL-26-treated group. Also, the M1-related proinflammatory cytokines TNFα and IL-6 were induced after IL-26 stimulation. Interestingly, IL-10, a cytokine marker of M2 macrophage, was also elevated after IL-26 stimulation. Moreover, the M1-like macrophage stimulated by IL-26 underwent cJUN, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 1 (STAT1) activation. Our findings suggested the role of IL-26 in synovial macrophages of active rheumatoid arthritis and provided a new insight into IL-26 as a candidate therapeutic target in rheumatoid arthritis.

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