-
Small (Weinheim An Der Bergstrasse,... Oct 2021Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to...
Macrophage polarization toward M1 phenotype (pro-inflammation) is closely associated with the destructive phase of periodontal inflammation. Nanoceria is verified to inhibit M1 polarization of macrophages by the favorable ability of reactive oxygen species (ROS) scavenging. However, the function of nanoceria on macrophage polarization toward M2 phenotype (anti-inflammation) in reparative phase of periodontal inflammation is quite limited. In this work, by introducing an antioxidant drug quercetin onto nano-octahedral ceria, synergistic and intense regulation of host immunity against periodontal disease is realized. Such nanocomposite can control the phenotypic switch of macrophages by not only inhibition of M1 polarization for suppressing the damage in the destructive phase but also promotion of M2 polarization for regenerating the surrounding tissues in reparative phase of periodontal disease. As-prepared nanocomposite can effectively increase the M2/M1 ratio of macrophage polarization in inflammatory cellular models by lipopolysaccharide stimulation. More importantly, the nanocomposite also exerts an improved therapeutic potential against local inflammation by significant downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines in an animal model with periodontal inflammation. Therefore, this newly developed nanomedicine is efficient in ROS scavenging and driving pro-inflammatory macrophages to the anti-inflammatory phenotype to eliminate inflammation, thereby providing a promising candidate for treating periodontal inflammation.
Topics: Animals; Inflammation; Macrophage Activation; Macrophages; Nanocomposites; Quercetin
PubMed: 34499411
DOI: 10.1002/smll.202101505 -
Trends in Immunology Dec 2023A binary classification of macrophage activation as inflammatory or resolving does not capture the diversity of macrophage states observed in tissues. However, framing... (Review)
Review
A binary classification of macrophage activation as inflammatory or resolving does not capture the diversity of macrophage states observed in tissues. However, framing macrophage activation as a continuous spectrum of states overlooks the intracellular and extracellular networks that regulate and coordinate macrophage responses. Here, we suggest that the systems biology concept of network motifs, which incorporate rules of local molecular interactions, is useful for reframing macrophage activation. Because network motifs can be used to regulate distinct biological functions, they offer a simplified unit that can be compared across organismal, tissue, and disease contexts. Moreover, defining macrophage states as combinations of functional modules regulated by network motifs offers a framework to ultimately predict and target macrophage responses arising in complex environments.
Topics: Humans; Macrophages; Phagocytosis; Systems Biology; Inflammation; Macrophage Activation
PubMed: 37949786
DOI: 10.1016/j.it.2023.10.009 -
Allergy Jun 2023Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined.
BACKGROUND
Dysregulation of circRNAs is associated with a variety of human diseases; however, its role in childhood asthma is undefined.
METHODS
The differential expression profiles of circRNAs were analyzed by microarray. The effects and mechanisms by which circRNAs influence macrophage activation were detected by quantitative real-time PCR, RNA immunoprecipitation assay, and chromatin immunoprecipitation assay, among others. The roles of circRNA and its host gene in asthma were tested in a cockroach allergen extract (CRE)-induced murine asthma model.
RESULTS
We identified 372 circRNAs that were differentially expressed in PBMCs of children with asthma as compared with healthy controls. A circRNA with unknown function, circS100A11, was dominantly expressed in monocytes and significantly upregulated in children with asthma. circS100A11 facilitated M2a macrophage activation by enhancing translation of its host gene, S100A11, and exacerbated lung inflammation in a CRE-induced murine asthma model with macrophage-specific overexpression of circS100A11. Mechanistically, circS100A11 promoted S100A11 translation by competitively binding to CAPRIN1 to decrease the suppression of CAPRIN1 upon S100A11 translation. Then, S100A11 liberated SP3 from nucleolin and promoted SP3 binding to the STAT6 promoter to enhance STAT6 expression and M2a macrophage activation. Macrophage-specific knockdown of S100A11 could alleviate lung inflammation in a CRE-induced murine asthma model in vivo.
CONCLUSIONS
circS100A11 and S100A11 promote M2a macrophage activation and lung inflammation in asthma model and may serve as potential therapeutic and diagnostic targets in children with asthma.
Topics: Humans; Child; Mice; Animals; RNA, Circular; Macrophage Activation; RNA; Pneumonia; Asthma; Cell Cycle Proteins
PubMed: 36104951
DOI: 10.1111/all.15515 -
Current Opinion in Biotechnology Apr 2021Macrophages are the prominent innate immune cells to combat infection and then restore tissue homeostasis after clearance of pathogens. Intracellular metabolic... (Review)
Review
Macrophages are the prominent innate immune cells to combat infection and then restore tissue homeostasis after clearance of pathogens. Intracellular metabolic reprogramming is required for macrophage activation and function, as such adaptations confer macrophages with sufficient energy and metabolites to support biosynthesis and diverse functions. During the last 10 years, knowledge in this field has been greatly extended by outstanding advances demonstrating that several metabolic intermediates possess the ability to directly control macrophage activation and effector functions by various mechanisms. Of note, citrate and succinate contribute to the inflammatory activation of macrophages while tricarboxylic acid cycle-derived metabolite itaconate has a variety of immunomodulatory effects. Such progress not only encourages a further exploration into the emerging new area immunometabolism, but also provides potential therapeutic targets to control unwanted inflammation due to infection.
Topics: Citric Acid Cycle; Humans; Inflammation; Macrophage Activation; Macrophages; Succinic Acid
PubMed: 33610128
DOI: 10.1016/j.copbio.2021.01.020 -
Frontiers in Cellular and Infection... 2020Macrophages are important effectors of tissue homeostasis, inflammation and host defense. They are equipped with an arsenal of pattern recognition receptors (PRRs)... (Review)
Review
Macrophages are important effectors of tissue homeostasis, inflammation and host defense. They are equipped with an arsenal of pattern recognition receptors (PRRs) necessary to sense microbial- or danger-associated molecular patterns (MAMPs/DAMPs) and elicit rapid energetically costly innate immunity responses to protect the organism. The interaction between cellular metabolism and macrophage innate immunity is however not limited to answering the cell's energy demands. Mounting evidence now indicate that in response to bacterial sensing, macrophages undergo metabolic adaptations that contribute to the induction of innate immunity signaling and/or macrophage polarization. In particular, intermediates of the glycolysis pathway, the Tricarboxylic Acid (TCA) cycle, mitochondrial respiration, amino acid and lipid metabolism directly interact with and modulate macrophage effectors at the epigenetic, transcriptional and post-translational levels. Interestingly, some intracellular bacterial pathogens usurp macrophage metabolic pathways to attenuate anti-bacterial defenses. In this review, we highlight recent evidence describing such host-bacterial immunometabolic interactions.
Topics: Bacterial Infections; Humans; Immunity, Innate; Macrophage Activation; Macrophages; Receptors, Pattern Recognition
PubMed: 33585278
DOI: 10.3389/fcimb.2020.607650 -
Trends in Immunology Jun 2021Tissue-resident macrophages (M) have recently emerged as a key rheostat capable of regulating the balance between organ health and disease. In most organs,... (Review)
Review
Tissue-resident macrophages (M) have recently emerged as a key rheostat capable of regulating the balance between organ health and disease. In most organs, ontogenetically and functionally distinct macrophage subsets fulfill a plethora of functions specific to their tissue environment. In this review, we summarize recent findings regarding the ontogeny and functions of macrophage populations in different mammalian tissues, describing how these cells regulate tissue homeostasis and how they can contribute to inflammation. Furthermore, we highlight new developments concerning certain general principles of tissue macrophage biology, including the importance of metabolism for understanding macrophage activation states and the influence of intrinsic and extrinsic factors on macrophage metabolic control. We also shed light on certain open questions in the field and how answering these might pave the way for tissue-specific therapeutic approaches.
Topics: Animals; Homeostasis; Inflammation; Macrophage Activation; Macrophages
PubMed: 33972166
DOI: 10.1016/j.it.2021.04.007 -
European Journal of Pharmacology Sep 2022Tumour-associated macrophages (TAMs) have been found to be of great importance in tumorigenesis and in promoting malignant progression, including tumour angiogenesis and... (Review)
Review
Tumour-associated macrophages (TAMs) have been found to be of great importance in tumorigenesis and in promoting malignant progression, including tumour angiogenesis and metastasis. Moreover, the TAM phenotype is more likely to be an M2 type. Transforming TAMs by M2-polarization into the tumour-suppressive M1-phenotype is an important approach for tumour therapy. In this review, we analysed the effects of the tumour microenvironment on macrophage phenotype-switching, including hypoxia and cytokines, and the mechanisms of drugs targeting TAMs. Furthermore, we analysed the effects of exosomes on macrophage polarization, phenotype switching of macrophages, and the mechanisms of lipid mediators targeting TAMs.
Topics: Humans; Macrophage Activation; Macrophages; Neoplasms; Phenotype; Tumor Microenvironment
PubMed: 36002039
DOI: 10.1016/j.ejphar.2022.175229 -
Aging Cell Jul 2023Macrophages adapt distinct pro-inflammatory (M1-like) and pro-resolving (M2-like) phenotypes with specific tasks in the immune response and tissue homeostasis. Altered...
Macrophages adapt distinct pro-inflammatory (M1-like) and pro-resolving (M2-like) phenotypes with specific tasks in the immune response and tissue homeostasis. Altered macrophage responses with age are causative for unresolved inflammation, so-called inflammaging, and lead to higher infection susceptibility with unfavorable progression. Here, we reveal molecular determinants of age-related changes in phenotypic functions of murine peritoneal macrophages (PM) by employing comprehensive mass spectrometry-based proteomics (4746 protein groups) and metabololipidomics (>40 lipid mediators). Divergent expression of various macrophage-specific marker proteins and signaling pathways indicates aberrant PM phenotypes in old mice which detrimentally impact their capabilities to release immunomodulatory chemokines and cytokines. We show that aging strikingly compromises the polarization process of macrophages to adapt either pro-inflammatory or pro-resolving phenotypes, thereby yielding aberrant and afunctional macrophage subtypes that cannot be readily assigned to either a typical M1 or M2 phenotype. In particular, the phenotypic adaptation of the bacteria-challenged metabololipidome in macrophages related to inflammation is severely limited by age, which persists across ex vivo polarization towards M1 and M2a macrophages. Our results establish distinct age-associated PM phenotypes outside of the simplified M1 and M2 dichotomy and challenge the dogma of increased pro-inflammatory macrophage pre-activation due to aging by revealing maladaptive functions throughout all phases of inflammation, including resolution.
Topics: Mice; Animals; Macrophage Activation; Proteomics; Inflammation; Aging; Immunity
PubMed: 37101405
DOI: 10.1111/acel.13856 -
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 -
Mucosal Immunology Dec 2023Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious health problems that manifest as acute respiratory failure in response to different...
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are serious health problems that manifest as acute respiratory failure in response to different conditions, including viral respiratory infections. Recently, the inhibitory properties of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) were demonstrated in allergic and viral airway inflammation. In this study, we investigate the implication of LAIR-1 in ALI/ARDS and explore the underlying mechanisms. Polyinosinic:polycytidylic acid, a synthetic analog of double-stranded RNA, was used to mimic acute inflammation in viral infections. We demonstrate that LAIR-1 is predominantly expressed on macrophages and regulates their recruitment to the lungs as well as their activation in response to polyinosinic:polycytidylic acid. Interestingly, LAIR-1 deficiency increases neutrophil recruitment as well as lung resistance and permeability. In particular, we highlight the capacity of LAIR-1 to regulate the secretion of CXCL10, considered a key marker of macrophage overactivation in acute lung inflammation. We also reveal in COVID-19-induced lung inflammation that LAIR1 is upregulated on lung macrophages in correlation with relevant immune regulatory genes. Altogether, our findings demonstrate the implication of LAIR-1 in the pathogenesis of ALI/ARDS by means of the regulation of macrophages, thereby providing the basis of a novel therapeutic target.
Topics: Humans; Macrophage Activation; Acute Lung Injury; Lung; Pneumonia; Inflammation; Respiratory Distress Syndrome; Poly C
PubMed: 37634572
DOI: 10.1016/j.mucimm.2023.08.003