scholarly journals Long Noncoding RNA Profiling from Fasciola Gigantica Excretory/Secretory Product-Induced M2 to M1 Macrophage Polarization

2018 ◽  
Vol 47 (2) ◽  
pp. 505-522 ◽  
Author(s):  
Honglin Luo ◽  
Yaoyao Zhang ◽  
Zhaoan Sheng ◽  
Tao Luo ◽  
Jie Chen ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Fasciola Gigantica ◽  
Differentially Expressed ◽  
Secretory Product ◽  
Peptidase Activity ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Network Analyses ◽  
M2 Polarization ◽  
M1 Macrophage

Background/Aims: Long noncoding RNAs (lncRNAs) are well known regulators of gene expression that play essential roles in macrophage activation and polarization. However, the role of lncRNA in Fasciola gigantica excretory/secretory products (ESP)-induced M2 polarization into M1 macrophages is unclear. Herein, we performed lncRNA profiling of lncRNAs and mRNAs during the ESP-induced macrophage polarization process. Methods: F. gigantica ESP was used to induce peritoneal cavity M2 macrophages in BALB/c mice (5-6 weeks old) in vivo, and these cells were subsequently isolated and stimulated with IFN-γ + LPS to induce M1 cells in vitro. LncRNA and mRNA profiling was performed via microarray at the end of both polarization stages. Results: In total, 2,844 lncRNAs (1,579 upregulated and 1,265 downregulated) and 1,782 mRNAs (789 upregulated and 993 downregulated) were differentially expressed in M2 macrophages compared to M1 macrophages, and six lncRNAs were identified during polarization. We selected 34 differentially expressed lncRNAs and mRNAs to validate the results of microarray analysis using quantitative real-time PCR (qPCR). Pathway and Gene Ontology (GO) analyses demonstrated that these altered transcripts were involved in multiple biological processes, particularly peptidase activity and carbohydrate metabolism. Furthermore, coding and non-coding gene (CNC) and mRNA-related ceRNA network analyses were conducted to predict lncRNA expression trends and the potential target genes of these lncRNAs and mRNAs. Moreover, we determined that four lncRNAs and four mRNAs might participate in F. gigantica ESP-induced M2 polarization into M1 macrophages. Conclusions: This study illustrates the basic profiling of lncRNAs and mRNAs during F. gigantica ESP-induced M2 polarization into M1 macrophages and deepens our understanding of the mechanism underlying this process.

scholarly journals GRK2 Mediated Abnormal Transduction of PGE2-EP4-cAMP-CREB Signaling Induces the Imbalance of Macrophages Polarization in Collagen-Induced Arthritis Mice

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1596 ◽  
Author(s):  
Xuezhi Yang ◽  
Susu Li ◽  
Yingjie Zhao ◽  
Siyu Li ◽  
Tianjiao Zhao ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Inflammatory Cells ◽  
Adenosine Monophosphate ◽  
Constant Stimulus ◽  
M2 Macrophage ◽  
Collagen Induced Arthritis ◽  
M1 Macrophages ◽  
M2 Polarization ◽  
Macrophages Polarization ◽  
M1 Macrophage

Rheumatoid arthritis (RA) is characterized by the massive infiltration of various chronic inflammatory cells in synovia. In synovial fluid of patients with RA, M1 macrophages are dominant among all subtypes of macrophages, the mechanisms of macrophages polarization imbalance in RA has not been fully illuminated. The prostaglandin E2 (PGE2) augments M2 polarization in part via the cyclic adenosine monophosphate (cAMP)-cyclic AMP responsive element binding (CREB) signaling. However, previous study found constant stimulus of PGE2 on fibroblast-like synovial cells of adjuvant arthritis rats induced the decrease of cAMP, which is primarily caused by G protein-coupled receptor kinase 2 (GRK2)-induced EP4 over- desensitization. Whether GRK2 mediated-EP4 over-desensitization reduces the level of cAMP and inhibits M2 polarization in RA is unclear. Here we observed M1 macrophages were dominant in peritoneal macrophages (PMs), bone-marrow-derived macrophages (BMMs) and synovial macrophages of collagen-induced arthritis (CIA) mice. PGE2 stimulated M2 polarization via the EP4-cAMP-CREB in normal mice, while failed to promote M2 polarization in the PMs of CIA mice. Further, we found the EP4 over-desensitization stimulated by PGE2 induced abnormal PGE2-cAMP-CREB signaling as well as the imbalance of macrophage polarization. Targeted disruption of GRK2 in Raw264.7 (RAW) through GRK2 siRNA or CRISPR/Cas9 downregulated the M1 macrophage markers, upregulated the M2 macrophage markers and the EP4 membrane localization. The reduced M1/M2 ratio and increased p-CREB expression were observed in BMMs and PMs of GRK2+/− mice. This study highlighted a novel role of GRK2 in regulating macrophages function in RA and provided new idea for precision treatment of RA.

scholarly journals Involvement of M1 Macrophage Polarization in Endosomal Toll-Like Receptors Activated Psoriatic Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Chih-Hao Lu ◽  
Chao-Yang Lai ◽  
Da-Wei Yeh ◽  
Yi-Ling Liu ◽  
Yu-Wen Su ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Macrophage Polarization ◽  
M2 Macrophages ◽  
Toll Like Receptors ◽  
Pathogenic Role ◽  
M1 Macrophages ◽  
Inflammatory Status ◽  
M1 Macrophage ◽  
Psoriatic Lesions

Psoriasis is a chronic inflammatory skin disorder that affects ~2%–3% of the worldwide population. Inappropriate and excessive activation of endosomal Toll-like receptors 7, 8, and 9 (TLRs 7–9) at the psoriatic site has been shown to play a pathogenic role in the onset of psoriasis. Macrophage is a major inflammatory cell type that can be differentiated into phenotypes M1 and M2. M1 macrophages produce proinflammatory cytokines, and M2 macrophages produce anti-inflammatory cytokines. The balance between these two types of macrophages determines the progression of various inflammatory diseases; however, whether macrophage polarization plays a role in psoriatic inflammation activated by endosomal TLRs has not been investigated. In this study, we investigated the function and mechanism of macrophages related to the pathogenic role of TLRs 7–9 in the progression of psoriasis. Analysis of clinical data in database revealed significantly increased expression of macrophage markers and inflammatory cytokines in psoriatic tissues over those in normal tissues. In animal studies, depletion of macrophages in mice ameliorated imiquimod, a TLR 7 agonist-induced psoriatic response. Imiquimod induced expression of genes and cytokines that are signature of M1 macrophage in the psoriatic lesions. In addition, treatment with this TLR 7 agonist shifted macrophages in the psoriatic lesions to a higher M1/M2 ratio. Both of the exogenous and endogenous TLR 7–9 ligands activated M1 macrophage polarization. M1 macrophages expressed higher levels of proinflammatory cytokines and TLRs 7–9 than M2 macrophages. These results suggest that by rendering macrophages into a more inflammatory status and capable of response to their ligands in the psoriatic sites, TLR 7–9 activation drives them to participate in endosomal TLR-activated psoriatic inflammation, resulting in an amplified inflammatory response. Our results also suggest that blocking M1 macrophage polarization could be a strategy which enables inhibition of psoriatic inflammation activated by these TLRs.

scholarly journals Prior Pro-inflammatory Polarization Changes the Macrophage Response to IL-4

2021 ◽  
Author(s):  
Erin M O'Brien ◽  
Kara L Spiller
Keyword(s):  
Tissue Repair ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Macrophage Response ◽  
M1 Macrophage ◽  
Gene And Protein Expression ◽  
M2 Phenotype

Tissue repair is largely regulated by diverse macrophage populations whose functions are timing- and context-dependent. The early phase of healing is dominated by pro-inflammatory macrophages, also known as M1, followed by the emergence of a distinct and diverse population that is collectively referred to as M2. The extent of the diversity of the M2 population is unknown. M2 macrophages may originate directly from circulating monocytes or from phenotypic switching of pre-existing M1 macrophages within the site of injury. The differences between these groups have not been investigated, but have major implications for understanding and treating pathologies characterized by deficient M2 activation, such as chronic wounds, which also exhibit diminished M1 macrophage behavior. This study investigated the influence of prior M1 activation on human macrophage polarization to an M2 phenotype in response to IL-4 treatment in vitro. Compared to unactivated (M0) macrophages, M1 macrophages upregulated several receptors that promote the M2 phenotype, including the primary receptor for IL-4. M1 activation also changed the macrophage response to treatment with IL-4, generating an M2-like phenotype with a distinct gene and protein expression signature compared to M2 macrophages prepared directly from M0 macrophages. Functionally, compared to M0-derived M2 macrophages, M1-derived M2 macrophages demonstrated increased migratory response to SDF-1α, and conditioned media from these macrophages promoted increased recruitment of endothelial cells in transwell assays. Together, these findings indicate the importance of prior M1 activation in regulating subsequent M2 behavior, and suggest that augmentation of M1 behavior may be a therapeutic target in dysfunctional tissue repair.

scholarly journals Iron Released after Cryo-Thermal Therapy Induced M1 Macrophage Polarization, Promoting the Differentiation of CD4+ T Cells into CTLs

2021 ◽  
Vol 22 (13) ◽  
pp. 7010
Author(s):  
Shicheng Wang ◽  
Man Cheng ◽  
Peng Peng ◽  
Yue Lou ◽  
Aili Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Antitumor Immunity ◽  
Macrophage Polarization ◽  
Thermal Therapy ◽  
High Plasticity ◽  
Antitumor Effects ◽  
M1 Macrophages ◽  
Splenic Macrophages ◽  
M1 Macrophage

Macrophages play critical roles in both innate and adaptive immunity and are known for their high plasticity in response to various external signals. Macrophages are involved in regulating systematic iron homeostasis and they sequester iron by phagocytotic activity, which triggers M1 macrophage polarization and typically exerts antitumor effects. We previously developed a novel cryo-thermal therapy that can induce the mass release of tumor antigens and damage-associated molecular patterns (DAMPs), promoting M1 macrophage polarization. However, that study did not examine whether iron released after cryo-thermal therapy induced M1 macrophage polarization; this question still needed to be addressed. We hypothesized that cryo-thermal therapy would cause the release of a large quantity of iron to augment M1 macrophage polarization due to the disruption of tumor cells and blood vessels, which would further enhance antitumor immunity. In this study, we investigated iron released in primary tumors, the level of iron in splenic macrophages after cryo-thermal therapy and the effect of iron on macrophage polarization and CD4+ T cell differentiation in metastatic 4T1 murine mammary carcinoma. We found that a large amount of iron was released after cryo-thermal therapy and could be taken up by splenic macrophages, which further promoted M1 macrophage polarization by inhibiting ERK phosphorylation. Moreover, iron promoted DC maturation, which was possibly mediated by iron-induced M1 macrophages. In addition, iron-induced M1 macrophages and mature DCs promoted the differentiation of CD4+ T cells into the CD4 cytolytic T lymphocytes (CTL) subset and inhibited differentiation into Th2 and Th17 cells. This study explains the role of iron in cryo-thermal therapy-induced antitumor immunity from a new perspective.

scholarly journals Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) modulates M1 macrophage polarization through TLR4/MAPK/NF-κB signaling pathways on murine macrophages

2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Se Hyang Hong ◽  
Jin Mo Ku ◽  
Ye Seul Lim ◽  
Hyo In Kim ◽  
Yong Cheol Shin ◽  
...  
Keyword(s):  
Digestive Enzymes ◽  
Macrophage Polarization ◽  
Water Extract ◽  
Cervus Nippon ◽  
No Production ◽  
M1 Macrophages ◽  
Murine Macrophages ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Cytokine Levels

The objective of this study was to investigate the effects of Cervus nippon var. mantchuricus water extract treated with digestive enzymes (CE) on the promotion of M1 macrophage polarization in murine macrophages. Macrophages polarize either to one phenotype after stimulation with LPS or IFN-γ or to an alternatively activated phenotype that is induced by IL-4 or IL-13. Cell viability of RAW264.7 cells was determined by WST-1 assay. NO production was measured by Griess assay. IL-6, IL-12, TNF-α, and iNOS mRNA levels were measured by RT-PCR. IL-6, IL-12, and IL-10 cytokine levels were determined by ELISA. TLR4/MAPK/NF-κB signaling in RAW264.7 cells was evaluated by western blotting. The level of NF-κB was determined by immunoblotting. CE induced the differentiation of M1 macrophages. CE promoted M1 macrophages to elevate NO production and cytokine levels. CE-stimulated M1 macrophages had enhanced IL-6, IL-12, and TNF-α. CE promoted M1 macrophages to activate TLR4/MAPK/NF-κB phosphorylation. M2 markers were downregulated, while M1 markers were upregulated in murine macrophages by CE. Consequently, CE has immunomodulatory activity and can be used to promote M1 macrophage polarization through the TLR4/MAPK/NF-κB signaling pathways.

scholarly journals Giant cell tumor stromal cells: osteoblast lineage-derived cells secrete IL-6 and IL-10 for M2 macrophages polarization

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9748
Author(s):  
Kuan Yang ◽  
Lihui Bao ◽  
Xiaoning He ◽  
Wanmin Zhao ◽  
Dongdong Fei ◽  
...  
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Stromal Cells ◽  
Macrophage Polarization ◽  
Giant Cells ◽  
Interleukin 10 ◽  
Cell Tumor ◽  
M2 Macrophages ◽  
M2 Polarization ◽  
Macrophages Polarization

Background The giant cell tumor (GCT) is a benign tumor which consists of three types cells: mononuclear histiocytic cells (MNHCs), multinuclear giant cells (MNGCs), and GCT stromal cells (GCTSCs). Numerous studies claim that GCTSCs have mesenchymal stem cells (MSCs) characters and play an important role in osteoclastogenesis; however, there are no research studies concerning macrophage polarization among GCT, which can be regarded as an ingredient for tumor aggression. Method We tested the effect of GCTSCs from three GCT samples which were collected from patients on proliferation, apoptosis and polarization of macrophage. Result In this article, we verified that GCTSCs expressed MSCs markers and had higher proliferation and relative lower differentiation abilities compared with BMMSCs. What’s more, we found a higher proportion of M2 macrophages among neoplasm. Co-culturing GCTSCs with macrophages resulted in prominent macrophage M2 polarization and increased the release of IL-6 (Interleukin-6) and IL-10 (Interleukin-10)from GCTSCs. In conclusion, GCTSCs, as originating from MSCs, can secret IL-6 and IL-10, which may play a significant role in macrophage M2 polarization.

scholarly journals Macrophage polarization in periodontal ligament stem cells enhanced periodontal regeneration

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jiaying Liu ◽  
Bin Chen ◽  
Jun Bao ◽  
Yangheng Zhang ◽  
Lang Lei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Periodontal Ligament ◽  
Early Stage ◽  
Macrophage Polarization ◽  
Periodontal Regeneration ◽  
Treated Group ◽  
M2 Macrophages ◽  
M2 Polarization ◽  
Tnf Α

Abstract Background The inflammation and regeneration process may be accompanied by the shift in the M1/M2 polarization of macrophages to adapt to extracellular signals. How the macrophages responded to the altered immunological environment in the periodontal niche after stem cell transplantation has never been explored. The purpose of present study is to investigate whether M1/M2 polarization of macrophages participated in the tissue homeostasis and wound healing during periodontal ligament stem cell (PDLSC)-based periodontal regeneration. Methods A rat periodontal defect model was utilized to observe the regeneration process in the PDLSC transplantation-enhanced periodontal repair. Dynamic changes in the markers of M1/M2 macrophages were observed on days 3, 7, and 21 post surgery. In addition, the outcome of regeneration was analyzed on day 21 after surgery. To further investigate the effect of PDLSCs on macrophage polarization, the conditioned medium of PDLSCs was utilized to treat M0, M1, and M2 macrophages for 24 h; markers of M1/M2 polarization were evaluated in macrophages. Results Elevated bone volume and average thickness of bone trabecular was observed in the PDLSC-treated group by micro-computed tomography on day 21. In addition, enhanced periodontal regeneration was observed in the PDLSC-treated group with cementum-like structure regeneration and collagen fiber formation, which inserted into the newly formed cementum. On day 3, PDLSC transplantation increased IL-10 level in the periodontal tissue, while decreased TNF-α in the early stage of periodontal regeneration. On day 7, enhanced CD163+ cell infiltration and heightened expression of markers of M2 macrophages were observed. Furthermore, conditioned medium from PDLSC culture induced macrophage polarization towards the anti-inflammatory phenotype by downregulating TNF-α and upregulating IL-10, Arg-1, and CD163 in vitro. Conclusions PDLSCs could induce macrophage polarization towards the M2 phenotype, and the shift in the polarization towards M2 macrophages in the early stage of tissue repair contributed to the enhanced periodontal regeneration after stem cell transplantation. Therefore, signals from the transplanted PDLSCs might alter the immune microenvironment to enhance periodontal regeneration.

scholarly journals Effect of Propofol on the Production of Inflammatory Cytokines by Human Polarized Macrophages

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Tsukasa Kochiyama ◽  
Xiaojia Li ◽  
Hitoshi Nakayama ◽  
Madoka Kage ◽  
Yui Yamane ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Signal Transduction Pathway ◽  
Induce Polarization ◽  
Human Macrophage ◽  
Related Factor ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Inflammatory Processes

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1β but did not affect TNF-α production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-β, and CD206, during M2 polarization. Propofol was similar to the GABAA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1β, but not TNF-α, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1β production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1β through the GABAA receptor and the Nrf2-mediated signal transduction pathway.

scholarly journals Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF-κB

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Yulong Mao ◽  
Baikui Wang ◽  
Xin Xu ◽  
Wei Du ◽  
Weifen Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Glycyrrhizic Acid ◽  
Macrophage Polarization ◽  
Herbal Medicines ◽  
Cell Surface Expression ◽  
M2 Macrophage ◽  
M1 Macrophages ◽  
Murine Bone Marrow ◽  
E Coli ◽  
M1 Macrophage

The roots and rhizomes ofGlycyrrhizaspecies (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran andE. coliK88 by BMDMs and decreased the intracellular survival ofE. coliK88 andS. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.

scholarly journals Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zhen-Shun Gan ◽  
Qian-Qian Wang ◽  
Jia-Hui Li ◽  
Xu-Liang Wang ◽  
Yi-Zhen Wang ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Macrophage Polarization ◽  
Reticuloendothelial System ◽  
Molecular Signature ◽  
Mrna Levels ◽  
M1 Macrophages ◽  
Iron Storage ◽  
Raw264.7 Macrophages ◽  
M1 Macrophage

Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin), a low level of iron export (ferroportin), and changes of iron regulators (hepcidin and transferrin receptors), which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1β, TNF-α, and iNOS produced by IFN-γ-polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

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