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Biomaterials Jun 2020Macrophages are among the first cells to interact with biomaterials and ultimately determine their integrative fate. Biomaterial surface characteristics like roughness...
Macrophages are among the first cells to interact with biomaterials and ultimately determine their integrative fate. Biomaterial surface characteristics like roughness and hydrophilicity can activate macrophages to an anti-inflammatory phenotype. Wnt signaling, a key cell proliferation and differentiation pathway, has been associated with dysregulated macrophage activity in disease. However, the role Wnt signaling plays in macrophage activation and response to biomaterials is unknown. The aim of this study was to characterize the regulation of Wnt signaling in macrophages during classical pro- and anti-inflammatory polarization and in their response to smooth, rough, and rough-hydrophilic titanium (Ti) surfaces. Peri-implant Wnt signaling in macrophage-ablated (MaFIA) mice instrumented with intramedullary Ti rods was significantly attenuated compared to untreated controls. Wnt ligand mRNA were upregulated in a surface modification-dependent manner in macrophages isolated from the surface of Ti implanted in C57Bl/6 mice. In vitro, Wnt mRNAs were regulated in primary murine bone-marrow-derived macrophages cultured on Ti in a surface modification-dependent manner. When macrophageal Wnt secretion was inhibited, macrophage sensitivity to both physical and biological stimuli was abrogated. Loss of macrophage-derived Wnts also impaired recruitment of mesenchymal stem cells and T-cells to Ti implants in vivo. Finally, inhibition of integrin signaling decreased surface-dependent upregulation of Wnt genes. These results suggest that Wnt signaling regulates macrophage response to biomaterials and that macrophages are an important source of Wnt ligands during inflammation and healing.
Topics: Animals; Biocompatible Materials; Macrophage Activation; Macrophages; Mice; Surface Properties; Titanium; Wnt Signaling Pathway
PubMed: 32179303
DOI: 10.1016/j.biomaterials.2020.119920 -
Aging Oct 2021Breast cancer is one of the most common malignant cancers among women. Cancer cells and adjacent cells determine the development of the disease. Tumor associated...
Breast cancer is one of the most common malignant cancers among women. Cancer cells and adjacent cells determine the development of the disease. Tumor associated macrophages (TAMs) are involved in the regulation of different stages of cancer progression. LncRNAs play an important role in tumor growth and metastasis. However, the function of lncRNA in macrophage and tumor cell interaction is poorly described. Here we reported that lncRNA SNHG1 functioned as a modulator of M2 macrophage polarization and regulated tumor growth and angiogenesis. We indicated that knockdown of SNHG1 inhibited M2 macrophage polarization by suppression of STAT6 phosphorylation. SNHG1 silencing significantly alleviated migration of MCF-7 cells and tube formation of Human Umbilical Vein Endothelial Cells (HUVEC). Furthermore, we found that implantation of cell mixture of MCF-7 cells and macrophages promoted tumor growth and angiogenesis. However, knockdown of SNHG1 in macrophages reversed that effect. Collectively, we demonstrated the important role of lncRNA SNHG1 in macrophages and breast cancer cells interaction. We highlight the essential effect of lncRNA in tumor progression and provide a new method for the prevention and treatment of breast tumor metastasis.
Topics: Animals; Breast Neoplasms; Female; Humans; MCF-7 Cells; Macrophage Activation; Mice; Mice, Nude; RAW 264.7 Cells; RNA, Long Noncoding; Tumor-Associated Macrophages
PubMed: 34618681
DOI: 10.18632/aging.203609 -
Frontiers in Immunology 2020
Topics: Animals; Humans; Immunity; Infections; Macrophage Activation; Macrophages
PubMed: 32547561
DOI: 10.3389/fimmu.2020.01078 -
Frontiers in Immunology 2020Endometriosis is a debilitating gynecological disease characterized by the extrauterine presence of endometrial-like tissues located on the peritoneal membrane and...
Endometriosis is a debilitating gynecological disease characterized by the extrauterine presence of endometrial-like tissues located on the peritoneal membrane and organs of the pelvic cavity. Notably, dysfunctional immune activation in women with endometriosis could also contribute to the development of disease. In particular, alternatively activated (M2) peritoneal macrophages are shown to aid peritoneal lesion development by promoting remodeling of extracellular matrix and neovascularization of lesions. However, the stimuli responsible for polarizing M2 macrophages in endometriosis remain elusive. Interleukin-17A (IL-17A) can induce M2 macrophage polarization in other disease models and IL-17A is elevated in the plasma and endometriotic lesions of women with endometriosis. In this study, we investigated whether IL-17A could induce macrophage recruitment and M2 polarization, while promoting endometriotic lesion growth through enhanced vascularization. By utilizing a co-culture of macrophage-like THP-1 cells with an endometriotic epithelial cell line, our results suggest that IL-17A indirectly induces M2 markers CCL17 and CD206 by interacting with endometriotic epithelial cells. Further, in a syngeneic mouse model of endometriosis, IL-17A treatment increased macrophages in the peritoneum, which were also M2 in phenotype. However, IL-17A treatment did not augment proliferation or vascularization of the lesion in the study time frame. These findings suggest that IL-17A may be a stimulus inducing the pathogenic polarization of macrophages into the M2 phenotype by first acting on the endometriotic lesion itself.
Topics: Cell Differentiation; Cells, Cultured; Cytokines; Endometriosis; Female; Gene Expression; Humans; Interleukin-17; Macrophage Activation; Macrophages, Peritoneal; Recombinant Proteins; THP-1 Cells
PubMed: 32117261
DOI: 10.3389/fimmu.2020.00108 -
Mediators of Inflammation 2023Macrophages are innate immune cells in the organism and can be found in almost tissues and organs. They are highly plastic and heterogeneous cells and can participate in... (Review)
Review
Macrophages are innate immune cells in the organism and can be found in almost tissues and organs. They are highly plastic and heterogeneous cells and can participate in the immune response, thereby playing a crucial role in maintaining the immune homeostasis of the body. It is well known that undifferentiated macrophages can polarize into classically activated macrophages (M1 macrophages) and alternatively activated macrophages (M2 macrophages) under different microenvironmental conditions. The directions of macrophage polarization can be regulated by a series of factors, including interferon, lipopolysaccharide, interleukin, and noncoding RNAs. To elucidate the role of macrophages in various autoimmune diseases, we searched the literature on macrophages with the PubMed database. Search terms are as follows: macrophages, polarization, signaling pathways, noncoding RNA, inflammation, autoimmune diseases, systemic lupus erythematosus, rheumatoid arthritis, lupus nephritis, Sjogren's syndrome, Guillain-Barré syndrome, and multiple sclerosis. In the present study, we summarize the role of macrophage polarization in common autoimmune diseases. In addition, we also summarize the features and recent advances with a particular focus on the immunotherapeutic potential of macrophage polarization in autoimmune diseases and the potentially effective therapeutic targets.
Topics: Humans; Macrophages; Inflammation; Lupus Nephritis; Arthritis, Rheumatoid; Lupus Erythematosus, Systemic; Macrophage Activation
PubMed: 37332618
DOI: 10.1155/2023/8821610 -
Cell Death & Disease Apr 2021Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the...
Exosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.
Topics: Animals; Autophagy; Exosomes; Glioma; Humans; Macrophage Activation; Male; Mice; Transfection; Tumor Microenvironment
PubMed: 33828078
DOI: 10.1038/s41419-021-03664-1 -
Frontiers in Immunology 2021Inhaled allergens promote inflammatory response, tissue damage, and airway hyperresponsiveness in the lungs, leading to allergic asthma. NLRP3, as an immune sensor of...
Inhaled allergens promote inflammatory response, tissue damage, and airway hyperresponsiveness in the lungs, leading to allergic asthma. NLRP3, as an immune sensor of infections and cellular stress, is associated with the development and exacerbation of asthma. However, the mechanism by which NLRP3 affects asthma requires further investigation. Here, we showed that inhaled house dust mite (HDM) promotes NLRP3 inflammasome activation in the lungs and specifically induces the maturation of caspase-1 and IL-1β in alveolar macrophages (AMs). Using -mutant mice, we found that NLRP3 promotes the inflammatory response and pathogenesis in HDM-induced allergic asthma in an inflammasome-dependent manner. Treatment with RRx-001, an NLRP3 inhibitor, significantly reduced inflammatory cell infiltration and mucus secretion in the airway. Our results showed that NLRP3 in myeloid cells promoted the development and progression of allergic asthma in an inflammasome-dependent manner. Small molecules targeting the NLRP3 inflammasome may provide new treatment options for this disease.
Topics: Allergens; Animals; Asthma; Biomarkers; Disease Models, Animal; Disease Susceptibility; Immunohistochemistry; Inflammasomes; Macrophage Activation; Macrophages, Alveolar; Mice; Mice, Knockout; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroglyphidae
PubMed: 34413860
DOI: 10.3389/fimmu.2021.718779 -
Small (Weinheim An Der Bergstrasse,... Apr 2022Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a...
Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.
Topics: Macrophage Activation; Macrophages; NF-kappa B; Polyesters
PubMed: 34816589
DOI: 10.1002/smll.202104112 -
Cells Aug 2023Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more... (Review)
Review
Sport concussion affects millions of athletes each year at all levels of sport. Increasing evidence demonstrates clinical and physiological recovery are becoming more divergent definitions, as evidenced by several studies examining blood-based biomarkers of inflammation and imaging studies of the central nervous system (CNS). Recent studies have shown elevated microglial activation in the CNS in active and retired American football players, as well as in active collegiate athletes who were diagnosed with a concussion and returned to sport. These data are supportive of discordance in clinical symptomology and the inflammatory response in the CNS upon symptom resolution. In this review, we will summarize recent advances in the understanding of the inflammatory response associated with sport concussion and broader mild traumatic brain injury, as well as provide an outlook for important research questions to better align clinical and physiological recovery.
Topics: Humans; Brain Concussion; Athletes; Central Nervous System; Inflammation; Macrophage Activation
PubMed: 37681861
DOI: 10.3390/cells12172128 -
Science Advances Apr 2021mA RNA modification is implicated in multiple cellular responses. However, its function in the innate immune cells is poorly understood. Here, we identified major mA...
mA RNA modification is implicated in multiple cellular responses. However, its function in the innate immune cells is poorly understood. Here, we identified major mA "writers" as the top candidate genes regulating macrophage activation by LPS in an RNA binding protein focused CRISPR screening. We have confirmed that deficient macrophages exhibited reduced TNF-α production upon LPS stimulation in vitro. Consistently, ;Cre mice displayed increased susceptibility to bacterial infection and showed faster tumor growth. Mechanistically, the transcripts of the gene encoding a negative regulator of TLR4 signaling were highly decorated by mA modification. METTL3 deficiency led to the loss of mA modification on mRNA and slowed down its degradation, resulting in a higher level of IRAKM, which ultimately suppressed TLR signaling-mediated macrophage activation. Our findings demonstrate a previously unknown role for METTL3-mediated mA modification in innate immune responses and implicate the mA machinery as a potential cancer immunotherapy target.
Topics: Adenosine; Animals; Clustered Regularly Interspaced Short Palindromic Repeats; Lipopolysaccharides; Macrophage Activation; Methyltransferases; Mice
PubMed: 33910903
DOI: 10.1126/sciadv.abd4742