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Pharmacological Research Nov 2018The activation or polarization of macrophages to pro- or anti-inflammatory states evolved as an adaptation to protect against a spectrum of biological threats. Such an... (Review)
Review
The activation or polarization of macrophages to pro- or anti-inflammatory states evolved as an adaptation to protect against a spectrum of biological threats. Such an adaptation engages pro-oxidative mechanisms and enables macrophages to neutralize and kill threatening organisms (e.g., viruses, bacteria, mold), limit cancerous growths, and enhance recovery and repair processes. The present study demonstrates that (1) many diverse pharmacological, chemical and physical agents can mediate a dose/concentration-dependent shift between pro- and anti-inflammatory activation states, and (2) these shifts in activation states display biphasic dose-response relationships that are characteristic of hormesis. This study also reveals that preconditioning-another form of hormesis-similarly mediates tissue protection by the polarization of macrophages, but in this case, towards an anti-inflammatory phenotype. This assessment supports the generalizability and significance of hormesis in biology, medicine, and public health and further extends it to encompass the hormetic activation of macrophages.
Topics: Animals; Hormesis; Humans; Macrophage Activation; Phenotype
PubMed: 30326267
DOI: 10.1016/j.phrs.2018.10.010 -
JCI Insight Oct 2021Macrophage proinflammatory activation is an important etiologic component of the development of insulin resistance and metabolic dysfunction in obesity. However, the...
Macrophage proinflammatory activation is an important etiologic component of the development of insulin resistance and metabolic dysfunction in obesity. However, the underlying mechanisms are not clearly understood. Here, we demonstrate that a mitochondrial inner membrane protein, adenine nucleotide translocase 2 (ANT2), mediates proinflammatory activation of adipose tissue macrophages (ATMs) in obesity. Ant2 expression was increased in ATMs of obese mice compared with lean mice. Myeloid-specific ANT2-knockout (ANT2-MKO) mice showed decreased adipose tissue inflammation and improved insulin sensitivity and glucose tolerance in HFD/obesity. At the molecular level, we found that ANT2 mediates free fatty acid-induced mitochondrial permeability transition, leading to increased mitochondrial reactive oxygen species production and damage. In turn, this increased HIF-1α expression and NF-κB activation, leading to proinflammatory macrophage activation. Our results provide a previously unknown mechanism for how obesity induces proinflammatory activation of macrophages with propagation of low-grade chronic inflammation (metaflammation).
Topics: Adenine Nucleotide Translocator 2; Animals; Disease Models, Animal; Female; Humans; Inflammation; Macrophage Activation; Male; Mice; Obesity
PubMed: 34676827
DOI: 10.1172/jci.insight.147033 -
Nature Immunology Jul 2019Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system... (Review)
Review
Unlike other cells in the body, immune cells have to be able to enter and adapt to life within diverse tissues. Immune cells develop within dedicated immune system organs, such as the bone marrow, thymus and lymphoid tissues, but also inhabit other tissues, wherein they not only provide defense against infection and malignancies but also contribute to homeostatic tissue function. Because different tissues have widely divergent metabolic rates and fuel requirements, this raises interesting questions about the adaptation of immune cells in specific tissues. When immune cells take up residence in different tissues, they develop a transcriptional signature that reflects adaptation to life and function within that tissue. Genes encoding metabolic-pathway proteins are strongly represented within these signatures, reflective of the importance of metabolic adaptation to tissue residence. In this Review, we discuss the available data on the metabolic adaptation of immune cells to life in different tissue sites, within the broader framework of how functional adaptation versus maladaptation in the niche can affect tissue homeostasis.
Topics: Adaptation, Biological; Animals; Biomarkers; Energy Metabolism; Homeostasis; Host-Pathogen Interactions; Humans; Immune System; Lymphocyte Activation; Macrophage Activation; Macrophages; Organ Specificity; Signal Transduction
PubMed: 31213715
DOI: 10.1038/s41590-019-0407-0 -
International Journal of Molecular... Dec 2023The aim of this Special Issue is to investigate macrophages' high plasticity and ability to differentiate/polarize in response to numerous stimuli in the context of...
The aim of this Special Issue is to investigate macrophages' high plasticity and ability to differentiate/polarize in response to numerous stimuli in the context of diseases, infections, and biomolecules exposition (immunomodulators) [...].
Topics: Macrophages; Immunologic Factors; Macrophage Activation; Adjuvants, Immunologic
PubMed: 38139238
DOI: 10.3390/ijms242417409 -
Frontiers in Endocrinology 2020Type-2 diabetes (T2D) is a disease of two etiologies: metabolic and inflammatory. At the cross-section of these etiologies lays the phenomenon of metabolic inflammation.... (Review)
Review
Type-2 diabetes (T2D) is a disease of two etiologies: metabolic and inflammatory. At the cross-section of these etiologies lays the phenomenon of metabolic inflammation. Whilst metabolic inflammation is characterized as systemic, a common starting point is the tissue-resident macrophage, who's successful physiological or aberrant pathological adaptation to its microenvironment determines disease course and severity. This review will highlight the key mechanisms in macrophage polarization, inflammatory and non-inflammatory signaling that dictates the development and progression of insulin resistance and T2D. We first describe the known homeostatic functions of tissue macrophages in insulin secreting and major insulin sensitive tissues. Importantly we highlight the known mechanisms of aberrant macrophage activation in these tissues and the ways in which this leads to impairment of insulin sensitivity/secretion and the development of T2D. We next describe the cellular mechanisms that are known to dictate macrophage polarization. We review recent progress in macrophage bio-energetics, an emerging field of research that places cellular metabolism at the center of immune-effector function. Importantly, following the advent of the metabolically-activated macrophage, we cover the known transcriptional and epigenetic factors that canonically and non-canonically dictate macrophage differentiation and inflammatory polarization. In closing perspectives, we discuss emerging research themes and highlight novel non-inflammatory or non-immune roles that tissue macrophages have in maintaining microenvironmental and systemic homeostasis.
Topics: Animals; Diabetes Mellitus, Type 2; Homeostasis; Humans; Insulin; Insulin Resistance; Macrophage Activation; Signal Transduction
PubMed: 32140136
DOI: 10.3389/fendo.2020.00062 -
Frontiers in Immunology 2024Macrophages are crucial cells in the human body's innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when... (Review)
Review
Macrophages are crucial cells in the human body's innate immunity and are engaged in a variety of non-inflammatory reactions. Macrophages can develop into two kinds when stimulated by distinct internal environments: pro-inflammatory M1-like macrophages and anti-inflammatory M2-type macrophages. During inflammation, the two kinds of macrophages are activated alternatively, and maintaining a reasonably steady ratio is critical for maintaining homeostasis . M1 macrophages can induce inflammation, but M2 macrophages suppress it. The imbalance between the two kinds of macrophages will have a significant impact on the illness process. As a result, there are an increasing number of research being conducted on relieving or curing illnesses by altering the amount of macrophages. This review summarizes the role of macrophage polarization in various inflammatory diseases, including autoimmune diseases (RA, EAE, MS, AIH, IBD, CD), allergic diseases (allergic rhinitis, allergic dermatitis, allergic asthma), atherosclerosis, obesity and type 2 diabetes, metabolic homeostasis, and the compounds or drugs that have been discovered or applied to the treatment of these diseases by targeting macrophage polarization.
Topics: Humans; Macrophages; Inflammation; Animals; Macrophage Activation; Hypersensitivity; Autoimmune Diseases
PubMed: 38660308
DOI: 10.3389/fimmu.2024.1352946 -
Methods (San Diego, Calif.) Jul 2024Long noncoding RNAs (lncRNA) are emerging players in regulation of gene expression and cell signaling and their dysregulation has been implicated in a multitude of human... (Review)
Review
Long noncoding RNAs (lncRNA) are emerging players in regulation of gene expression and cell signaling and their dysregulation has been implicated in a multitude of human diseases. Recent studies from our laboratory revealed that lncRNAs play critical roles in cytokine regulation, inflammation, and metabolism. We demonstrated that lncRNA HOTAIR, which is a well-known regulator of gene silencing, plays critical roles in modulation of cytokines and proinflammatory genes, and glucose metabolism in macrophages during inflammation. In addition, we recently discovered a series of novel lncRNAs that are closely associated with inflammation and macrophage activation. We termed these as long-noncoding inflammation associated RNAs (LinfRNAs). We are currently engaged in the functional characterization of these hLinfRNAs (human LinfRNAs) with a focus on their roles in inflammation, and we are investigating their potential implications in chronic inflammatory human diseases. Here, we have summarized experimental methods that have been utilized for the discovery and functional characterization of lncRNAs in inflammation and macrophage activation.
Topics: RNA, Long Noncoding; Humans; Macrophage Activation; Inflammation; Macrophages; Animals; Gene Expression Regulation; Cytokines
PubMed: 38703879
DOI: 10.1016/j.ymeth.2024.05.001 -
Journal of Molecular and Cellular... Dec 2015During the past decade, the crucial role of microRNAs (miRs) controlling tissue homeostasis and disease in the cardiovascular system has become widely recognized. By... (Review)
Review
During the past decade, the crucial role of microRNAs (miRs) controlling tissue homeostasis and disease in the cardiovascular system has become widely recognized. By controlling the expression levels of their targets, several miRs have been shown to modulate the function of endothelial cells, vascular smooth muscle cells, and macrophages, thereby regulating the development and progression of atherosclerosis. For instance, miR-155 can exacerbate early stages of atherosclerosis by increasing the inflammatory activation and disturbing efficient lipid handling in macrophages. Conversely, miRs can exert atheroprotective roles, as has been established for the complementary miR-126 strand pair, which forms a dual system sustaining the endothelial proliferative reserve and promoting endothelial regeneration to counteract atherogenic effects of disturbed flow and hyperlipidemia. Under some conditions, miRs are released from cells and are transported by microvesicles, ribonucleoprotein complexes, and lipoproteins, being remarkably stable in circulation. Conferred by such delivery modules, miRs can regulate target mRNAs in recipient cells, representing a new tool for cell-cell communication in the context of atherosclerotic disease. Here, we will discuss novel aspects of miR-mediated regulatory mechanisms, namely the regulation by competing RNA targets, miRNA tandems, or complementary miR strand pairs, as well as their potential diagnostic and therapeutic value in atherosclerosis. This article is part of a Special Issue entitled 'Non-coding RNAs'.
Topics: Animals; Atherosclerosis; Gene Expression Regulation; Humans; Inflammation; Macrophage Activation; MicroRNAs; Models, Biological
PubMed: 25450610
DOI: 10.1016/j.yjmcc.2014.10.021 -
Allergy Jun 2018Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve... (Review)
Review
Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve distinct innate immunological metabolic functions. IFN-γ or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or "classically activated" phenotype that participates in defense against intracellular pathogens. IL-4, IL-13, or chitin polarizes macrophages toward the M2, or "alternatively activated" phenotype, which defends against multicellular nematodes and fungi. As macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here, we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1-mediated inflammation in adipose tissue enhances M2-mediated inflammation in the asthmatic lung.
Topics: Animals; Asthma; Biomarkers; Chronic Disease; Europe; Host-Pathogen Interactions; Humans; Hygiene Hypothesis; Hypoxia; Macrophage Activation; Macrophages; Obesity; Organ Specificity; Phenotype; Respiratory System
PubMed: 29178573
DOI: 10.1111/all.13369 -
BMB Reports Nov 2022Macrophage activation has long been implicated in a myriad of human pathophysiology, particularly in the context of the dysregulated capacities of an unleashing... (Review)
Review
Macrophage activation has long been implicated in a myriad of human pathophysiology, particularly in the context of the dysregulated capacities of an unleashing intracellular or/and extracellular inflammatory response. A growing number of studies have functionally coupled the macrophages' inflammatory capacities with dynamic metabolic reprogramming which occurs during activation, albeit the results have been mostly interpreted through classic metabolism point of view; macrophages take advantage of the rewired metabolism as a source of energy and for biosynthetic precursors. However, a specific subset of metabolic products, namely immune-modulatory metabolites, has recently emerged as significant regulatory signals which control inflammatory responses in macrophages and the relevant extracellular milieu. In this review, we introduce recently highlighted immuno-modulatory metabolites, with the aim of understanding their physiological and pathological relevance in the macrophage inflammatory response. [BMB Reports 2022; 55(11): 519-527].
Topics: Humans; Macrophage Activation; Macrophages; Immunomodulation; Inflammation
PubMed: 36195564
DOI: 10.5483/BMBRep.2022.55.11.128