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Cells Apr 2020Interleukin 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...
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.
Topics: Animals; Cell Differentiation; Cell Polarity; Humans; Interleukins; Macrophage Activation; Macrophages; Mice; NF-kappa B; Phenotype; Proto-Oncogene Proteins c-jun; RAW 264.7 Cells
PubMed: 32290250
DOI: 10.3390/cells9040938 -
Advanced Materials (Deerfield Beach,... Nov 2020Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating...
Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.
Topics: Animals; Cell Line, Tumor; Genetic Engineering; Humans; Immunotherapy; Macrophages; Mice; Nanomedicine; Nanoparticles; Neoplasms
PubMed: 33089578
DOI: 10.1002/adma.202004853 -
Journal of the American College of... Dec 2019Macrophages and fibroblasts are 2 major cell types involved in healing after myocardial infarction (MI), contributing to myocardial remodeling and fibrosis. Post-MI...
BACKGROUND
Macrophages and fibroblasts are 2 major cell types involved in healing after myocardial infarction (MI), contributing to myocardial remodeling and fibrosis. Post-MI fibrosis progression is characterized by a decrease in cardiac macrophage content.
OBJECTIVES
This study explores the potential of macrophages to express fibroblast genes and the direct role of these cells in post-MI cardiac fibrosis.
METHODS
Prolonged in vitro culture of human macrophages was used to evaluate the capacity to express fibroblast markers. Infiltrating cardiac macrophages was tracked in vivo after experimental MI of LysM(Cre);ROSA26(EYFP) transgenic mice. The expression of Yellow Fluorescent Protein (YFP) in these animals is restricted to myeloid lineage allowing the identification of macrophage-derived fibroblasts. The expression in YFP-positive cells of fibroblast markers was determined in myocardial tissue sections of hearts from these mice after MI.
RESULTS
Expression of the fibroblast markers type I collagen, prolyl-4-hydroxylase, fibroblast specific protein-1, and fibroblast activation protein was evidenced in YFP-positive cells in the heart after MI. The presence of fibroblasts after MI was evaluated in the hearts of animals after depletion of macrophages with clodronate liposomes. This macrophage depletion significantly reduced the number of Mac3Col1A1 cells in the heart after MI.
CONCLUSIONS
The data provide both in vitro and in vivo evidence for the ability of macrophages to transition and adopt a fibroblast-like phenotype. Therapeutic manipulation of this macrophage-fibroblast transition may hold promise for favorably modulating the fibrotic response after MI and after other cardiovascular pathological processes.
Topics: Animals; Biomarkers; Cell Transdifferentiation; Fibroblasts; Humans; Macrophages; Mice, Transgenic; Myocardial Infarction
PubMed: 31856969
DOI: 10.1016/j.jacc.2019.10.036 -
Journal of Immunology Research 2019Atherosclerosis is the main pathological basis for the occurrence of most cardiovascular diseases, the leading global health threat, and a great burden for society. It... (Review)
Review
Atherosclerosis is the main pathological basis for the occurrence of most cardiovascular diseases, the leading global health threat, and a great burden for society. It has been well established that atherosclerosis is not only a metabolic disorder but also a chronic, sterile, and maladaptive inflammatory process encompassing both innate and adaptive immunity. Macrophages, the major immune cell population in atherosclerotic lesions, have been shown to play critical roles in all stages of atherosclerosis, including the initiation and progression of advanced atherosclerosis. Macrophages have emerged as a novel potential target for antiatherosclerosis therapy. In addition, the macrophage phenotype is greatly influenced by microenvironmental stimuli in the plaques and presents complex heterogeneity. This article reviews the functions of macrophages in different stages of atherosclerosis, as well as the phenotypes and functions of macrophage subsets. New treatment strategies based on macrophage-related inflammation are also discussed.
Topics: Animals; Atherosclerosis; Biomarkers; Cytokines; Disease Susceptibility; Drug Discovery; Humans; Inflammation Mediators; Macrophage Activation; Macrophages; Molecular Targeted Therapy; Monocytes; Plaque, Atherosclerotic
PubMed: 31886303
DOI: 10.1155/2019/4354786 -
Trends in Immunology Apr 2024Macrophages are vital tissue components involved in organogenesis, maintaining homeostasis, and responses to disease. Mouse models have significantly improved our... (Review)
Review
Macrophages are vital tissue components involved in organogenesis, maintaining homeostasis, and responses to disease. Mouse models have significantly improved our understanding of macrophages. Further investigations into the characteristics and development of human macrophages are crucial, considering the substantial anatomical and physiological distinctions between mice and humans. Despite challenges in human macrophage research, recent studies are shedding light on the ontogeny and function of human macrophages. In this opinion, we propose combinations of cutting-edge approaches to examine the diversity, development, niche, and function of human tissue-resident macrophages. These methodologies can facilitate our exploration of human macrophages more efficiently, ideally providing new therapeutic avenues for macrophage-relevant disorders.
Topics: Humans; Mice; Animals; Macrophages; Organogenesis; Homeostasis; Disease Models, Animal
PubMed: 38580575
DOI: 10.1016/j.it.2024.02.007 -
Journal of Immunology Research 2020Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term... (Review)
Review
Atherosclerosis (AS), a typical chronic inflammatory vascular disease, is the main pathological basis of ischemic cardio/cerebrovascular disease (CVD). Long-term administration was characterized with low efficacy and serious side effects, while the macrophages with attractive intrinsic homing target have great potential in the efficient and safe management of AS. In this review, we focused on the systematical summary of the macrophage-based therapies in AS management, including macrophage autophagy, polarization, targeted delivery, microenvironment-triggered drug release, and macrophage- or macrophage membrane-based drug carrier. In conclusion, macrophage-based therapies have great promise to effectively manage AS in future research and clinic translation.
Topics: Animals; Atherosclerosis; Autophagy; Cardiovascular Agents; Cell Membrane; Disease Models, Animal; Drug Carriers; Humans; Inflammasomes; Macrophage Activation; Macrophages
PubMed: 32411803
DOI: 10.1155/2020/8131754 -
Cold Spring Harbor Perspectives in... Dec 2022Monocytes/macrophages are key components of the body's innate ability to restore tissue function after injury. In most tissues, both embryo-derived tissue-resident... (Review)
Review
Monocytes/macrophages are key components of the body's innate ability to restore tissue function after injury. In most tissues, both embryo-derived tissue-resident macrophages and recruited blood monocyte-derived macrophages contribute to the injury response. The developmental origin of injury-associated macrophages has a major impact on the outcome of the healing process. Macrophages are abundant at all stages of repair and coordinate the progression through the different phases of healing. They are highly plastic cells that continuously adapt to their environment and acquire phase-specific activation phenotypes. Advanced omics methodologies have revealed a vast heterogeneity of macrophage activation phenotypes and metabolic status at injury sites in different organs. In this review, we highlight the role of the developmental origin, the link between the wound phase-specific activation state and metabolic reprogramming as well as the fate of macrophages during the resolution of the wounding response.
Topics: Macrophages; Macrophage Activation; Wound Healing
PubMed: 36041784
DOI: 10.1101/cshperspect.a041216 -
Experimental & Molecular Medicine Sep 2023Macrophages are essential innate immune cells found throughout the body that have protective and pathogenic functions in many diseases. When activated, macrophages can... (Review)
Review
Macrophages are essential innate immune cells found throughout the body that have protective and pathogenic functions in many diseases. When activated, macrophages can mediate the phagocytosis of dangerous cells or materials and participate in effective tissue regeneration by providing growth factors and anti-inflammatory molecules. Ex vivo-generated macrophages have thus been used in clinical trials as cell-based therapies, and based on their intrinsic characteristics, they outperformed stem cells within specific target diseases. In addition to the old methods of generating naïve or M2 primed macrophages, the recently developed chimeric antigen receptor-macrophages revealed the potential of genetically engineered macrophages for cell therapy. Here, we review the current developmental status of macrophage-based cell therapy. The findings of important clinical and preclinical trials are updated, and patent status is investigated. Additionally, we discuss the limitations and future directions of macrophage-based cell therapy, which will help broaden the potential utility and clinical applications of macrophages.
Topics: Macrophages; Phagocytosis; Cell- and Tissue-Based Therapy; Anti-Inflammatory Agents
PubMed: 37653035
DOI: 10.1038/s12276-023-01068-z -
European Journal of Immunology Aug 2021The term 'macrophage' encompasses tissue cells that typically share dependence on the same transcriptional regulatory pathways (e.g. the transcription factor PU.1) and... (Review)
Review
The term 'macrophage' encompasses tissue cells that typically share dependence on the same transcriptional regulatory pathways (e.g. the transcription factor PU.1) and growth factors (e.g. CSF1/IL-34). They share a core set of functions that largely arise from a uniquely high phagocytic capacity manifest in their ability to clear dying cells, pathogens and scavenge damaged, toxic or modified host molecules. However, macrophages demonstrate a remarkable degree of tissue-specific functionality and have diverse origins that vary by tissue site and inflammation status. With our understanding of this diversity has come an appreciation of the longevity and replicative capacity of tissue-resident macrophages and thus the realisation that macrophages may persist through tissue perturbations and inflammatory events with important consequences for cell function. Here, we discuss our current understanding of the parameters that regulate macrophage survival and function, focusing on the relative importance of the tissue environment versus cell-intrinsic factors, such as origin, how long a cell has been resident within a tissue and prior history of activation. Thus, we reconsider the view of macrophages as wholly plastic cells and raise many unanswered questions about the relative importance of cell life-history versus environment in macrophage programming and function.
Topics: Animals; Humans; Macrophages
PubMed: 34107057
DOI: 10.1002/eji.202048881 -
Advances in Experimental Medicine and... 2020Macrophages represent one of the most diverse immunocyte populations, constantly shifting between various phenotypes/functional states. In addition to execution of vital... (Review)
Review
Macrophages represent one of the most diverse immunocyte populations, constantly shifting between various phenotypes/functional states. In addition to execution of vital functions in normal physiological conditions, macrophages represent a key contributing factor in the pathogenesis of some of the most challenging diseases, such as chronic inflammatory disorders, diabetes and its complications, and cancer. Macrophage polarization studies focus primarily on cytokine-mediated mechanisms. However, to explore the full spectrum of macrophage action, additional, non-cytokine pathways responsible for altering macrophage phenotype have to be taken into consideration as well. Heparanase, the only known mammalian endoglycosidase that cleaves heparan sulfate glycosaminoglycans, has been shown to contribute to the altered macrophage phenotypes in vitro and in numerous animal models of inflammatory conditions, occurring either in the presence of microbial products or in the setting of non-infectious "aseptic" inflammation. Here we discuss the involvement of heparanase in shaping macrophage responses and provide information that may help to establish the rationale for heparanase-targeting interventions aimed at preventing abnormal macrophage activation in various disorders.
Topics: Animals; Glucuronidase; Heparitin Sulfate; Humans; Macrophage Activation; Macrophages
PubMed: 32274721
DOI: 10.1007/978-3-030-34521-1_17