scholarly journals Stimulation of α7 Nicotinic Acetylcholine Receptor by Nicotine Suppresses Decidual M1 Macrophage Polarization Against Inflammation in Lipopolysaccharide-Induced Preeclampsia-Like Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinjia Han ◽  
Wei Li ◽  
Ping Li ◽  
Zheng Zheng ◽  
Baohua Lin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Inflammatory Cytokines ◽  
Macrophage Polarization ◽  
Regulatory Role ◽  
Trophoblast Invasion ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotine Treatment ◽  
M1 Macrophage ◽  
M1 Phenotype ◽  
M2 Phenotype

Changes in decidual macrophage polarization affect local inflammatory microenvironment and lead to adverse pregnancy outcomes. However, the regulatory mechanism of macrophage polarization in preeclampsia (PE) remains unclear. In this study, we found that α7nAChR expression was significantly down-regulated in decidual macrophages in PE patients compared to normal pregnant women, accompanied by a reduced proportion of M2 phenotype and an increased proportion of M1 phenotype; these results suggested that the reduced α7nAChR activity might contribute to changes in the polarization of decidual macrophages. Then, we further investigated the regulatory role of α7nAChR activation by nicotine on decidual macrophage polarization and placental remodeling in the PE-like mouse model. The PE mice were obtained by i.p. injection of 10 µg/kg lipopolysaccharide (LPS) gestational day (GD) 13, and 40 µg/kg LPS daily until GD16. Subcutaneous injection of 1.0 mg/kg nicotine was administrated from GD14 to GD18. Nicotine treatment increased the decreased M2 phenotype and inhibited the increased M1 phenotype in decidua of pregnant mice induced by LPS. The levels of pro-inflammatory cytokines in decidua were higher but the levels of anti-inflammatory cytokines were lower in PE mice compared to the controls, nicotine reversed these changes. The level of choline acetyltransferase (CHAT) was reduced in the LPS-treated group, it was increased following nicotine treatment. Damage of spiral artery remodeling and down-regulation of markers related to trophoblast invasion in placentas were found in PE mice; nicotine improved these pathological structures of placentas. α-bungarotoxin (α-BGT) which is specific antagonist for α7nAChR could abolish the effects of nicotine on decidual macrophage polarization, trophoblast arrangement and vascular structure in placental tissue in PE mice. These results suggest that α7nAChR plays an important regulatory role in maternal-fetal inflammation and placental remodeling in preeclampsia and may provide a theoretical basis for the discovery of new strategies for preeclampsia.

Abstract 553: Siglec-1 (CD169) on Monocytes/Macrophages: A New Receptor For Extracellular Self-RNA in Triggering Inflammatory Responses via the Sheddase TACE/ADAM17

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hector A Cabrera-Fuentes ◽  
Klaus T Preissner ◽  
William A Boisvert
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Transmembrane Protein ◽  
Macrophage Polarization ◽  
Extracellular Rna ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Phenotype Markers ◽  
Anti Inflammatory

As an important component of atherosclerosis, monocytes/macrophages respond to external stimuli with rapid changes in their expression of many inflammation-related genes to undergo polarization towards the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotype. Although sialoadhesin (Sn), also known as SIGLEC-1 or CD169, is a transmembrane protein receptor expressed on monocytes and macrophages whether it has a role in macrophage polarization and ultimately, macrophage-driven atherogenesis, has not been investigated. We have previously shown that, independently of Toll-like receptor signaling, extracellular RNA (eRNA) could exert pro-thrombotic and pro-inflammatory properties in the cardiovascular system by inducing cytokine mobilization. In the current study, recombinant mouse macrophage CSF[[Unable to Display Character: –]]driven bone marrow-derived macrophage (BMDM) differentiation was found to be skewed towards the M1 phenotype by exposure of cells to eRNA. This resulted in up-regulation of inflammatory markers, whereas anti-inflammatory genes were significantly down-regulated by eRNA. Interestingly, eRNA was released from BMDM under hypoxia and induced TNF-α liberation by activating TNF-α converting enzyme (TACE) to provoke inflammation. Conversely, TNF-α promoted eRNA release, especially under hypoxia, feeding a vicious cycle of cell damage. Administration of RNase1 or TAPI (a TACE-inhibitor) prevented the production of inflammatory mediators. Murine BMDM isolated from mice deficient in sialoadhesin had the opposite reaction to eRNA treatment with a prominent down-regulation of pro-inflammatory cytokines/M1 phenotype markers, while anti-inflammatory cytokines/M2 phenotype markers were significantly raised. In keeping with the proposed role of eRNA as a pro-inflammatory “alarm signal”, these data further shed light on the role of eRNA in macrophage function in the context of chronic inflammatory diseases such as atherosclerosis. The identification of sialoadhesin as putative eRNA recognition site on macrophages may allow further investigation of the underlying mechanisms of eRNA-macrophage interaction and related signal transduction pathways. Siglec-1 thereby may provides a new target to treat eRNA-mediated vascular diseases.

scholarly journals The Degree of Helicobacter pylori Infection Affects the State of Macrophage Polarization through Crosstalk between ROS and HIF-1α

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Ying Lu ◽  
Jianfang Rong ◽  
Yongkang Lai ◽  
Li Tao ◽  
Xiaogang Yuan ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Macrophage Polarization ◽  
Polarization State ◽  
Hypoxia Inducible Factor ◽  
Mtor Pathway ◽  
Raw 264.7 Cells ◽  
Gastric Lesions ◽  
M1 Phenotype ◽  
H Pylori ◽  
M2 Phenotype

Background and Objective. Helicobacter pylori (H. pylori) is involved in macrophage polarization, but the specific mechanism is not well understood. Therefore, this study is aimed at investigating the effects of the degree of H. pylori infection on the macrophage polarization state and the crosstalk between reactive oxygen species (ROS) and hypoxia-inducible factor 1 α (HIF-1α) in this process. Methods. The expression of CD86, CD206, and HIF-1α in the gastric mucosa was evaluated through immunohistochemistry. RAW 264.7 cells were cocultured with H. pylori at various multiplicities of infection (MOIs), and iNOS, CD86, Arg-1, CD206, and HIF-1α expression was detected by Western blot, PCR, and ELISA analyses. ROS expression was detected with the fluorescent probe DCFH-DA. Macrophages were also treated with the ROS inhibitor NAC or HIF-1α inhibitor YC-1. Results. Immunohistochemical staining revealed that the macrophage polarization state was associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori affected macrophage polarization, and H. pylori enhanced the expression of ROS and HIF-1α in macrophages. A low MOI of H. pylori promoted both the M1 and M2 phenotypes, while a high MOI suppressed the M2 phenotype. Furthermore, ROS inhibition attenuated HIF-1α expression and switched macrophage polarization from M1 to M2. However, HIF-1α inhibition suppressed ROS expression and inhibited both the M1 phenotype and the M2 phenotype. Inhibition of ROS or HIF-1α also suppressed the activation of the Akt/mTOR pathway, which was implicated in H. pylori-induced macrophage polarization. Conclusions. Macrophage polarization is associated with the progression of gastric lesions and state of H. pylori infection. The MOI of H. pylori influences the macrophage polarization state. Crosstalk between ROS and HIF-1α regulates H. pylori-induced macrophage polarization via the Akt/mTOR pathway.

scholarly journals Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Xian Jin ◽  
Tongqing Yao ◽  
Zhong’e Zhou ◽  
Jian Zhu ◽  
Song Zhang ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Macrophage Polarization ◽  
M2 Macrophage ◽  
Advanced Glycation ◽  
Alternatively Activated Macrophages ◽  
M1 Macrophage ◽  
Glycation End Products ◽  
End Products ◽  
Patients With Diabetes ◽  
M1 Phenotype

Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation.

scholarly journals Melatonin Maintains Macrophage M1 Phenotype to Reverse LPS-stimulated Tumor Immune Tolerance

2020 ◽  
Author(s):  
Yukun Lin ◽  
Mengdi Zhang ◽  
Lin Zhou ◽  
Yuehua Wang ◽  
Mengqi Wang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Immune Tolerance ◽  
Bacterial Infections ◽  
Macrophage Polarization ◽  
Surface Lipid ◽  
Lps Challenge ◽  
Stat3 Signaling ◽  
M1 Phenotype ◽  
M2 Phenotype

Abstract Background: Lipopolysaccharide (LPS) is a potent trigger of macrophage-mediated inflammation and its repeated stimulation results in immune tolerance. This study is to explore the cellular mechanisms of LPS-mediated tumor immune tolerance and to investigate whether melatonin can reverse this tolerance. Methods: The effect of melatonin and LPS on macrophages was assessed by cell proliferation, morphological changes, phagocytosis and autophagy in vitro. The tumor-preventing effect of melatonin and LPS were evaluated in the urethane-induced lung carcinoma model and in the H22 liver cancer allograft model. Immunofluorescence, immunohistochemistry and ELISA were used to examine protein expression. The related targets and pathways of melatonin were predicted by comprehensive bioinformatics, and the clinical association of bacterial infections and survival was evaluated in cancer patients by meta-analysis.Results: In vitro，Raw264.7 macrophages were polarized toward the M1 phenotype by single LPS administration but toward the M2 phenotype by repeated LPS administration. Interestingly, combination treatment with repeated LPS and 10 µM melatonin prevented macrophage polarization toward the M2-like phenotype and exerted lasting antitumor efficacy. In the urethane-induced lung carcinoma model, repeated LPS administration stimulated macrophage polarization toward the M2 phenotype and promoted lung carcinogenesis, which was abrogated by macrophage depletion, while melatonin alone or in combination with repeated LPS challenge restored M1-like macrophages and prevented carcinogenesis. In the H22 liver cancer allograft model, melatonin maintained the macrophage phenotype and promoted the tumor-suppressing effect of repeated LPS challenge. Furthermore, we found that macrophages repeatedly stimulated with LPS had a high level of surface lipid rafts that mediated PI3K/AKT and JAK2/STAT3 signaling and prevented both LPS sensitivity and immune response by self-expression of PD-L1 and surface expression of PD-1 receptor on NK cells, whereas melatonin decreased surface lipid rafts and PI3K/AKT and JAK2/STAT3 signaling. Finally, we conducted a comprehensive bioinformatics analysis of melatonin-relevant targets and pathways involved in M2 macrophage polarization and evaluated the clinical associations of bacterial infections and survival in cancer patients. Conclusions: This study suggests a function of melatonin in regulating macrophage polarization to maintain LPS-stimulated tumor immune surveillance.

scholarly journals Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization

2020 ◽  
Author(s):  
Chen Wang ◽  
Rongrong Zhang ◽  
Qi Zhang ◽  
Huixiang Jin ◽  
Chenghua Wei ◽  
...  
Keyword(s):  
Mouse Model ◽  
Choroidal Neovascularization ◽  
Inflammatory Cytokines ◽  
Laser Photocoagulation ◽  
Macrophage Polarization ◽  
Fold Change ◽  
Lesion Area ◽  
M2 Polarization ◽  
Intravitreal Aflibercept ◽  
Fas L

Purpose: The purpose of our study was to investigate the profiles of inflammatory cytokines and the macrophage polarization gene in a choroidal neovascularization (CNV) mouse model before and after intravitreal aflibercept treatment. Methods: The CNV mouse model was conducted by laser photocoagulation. A total of 58 cytokines were measured by multiplex mouse cytokine antibody array. The macrophage polarization genes were tested by reverse transcription polymerase chain reaction. The relationship between the cytokines and the CNV lesion area was analyzed by correlation. Results: MIP-1a on day 3 after laser photocoagulation, MCP-5 and Fas-L on day 7, and IL-15 and IL-7 on day 14 were significantly upregulated (p< 0.001, fold change > 10.0). After the intravitreal aflibercept treatment, GM-CSF and MCP-1 on day 3 and TIMP-1 on days 7 and 14 were the most significantly upregulated cytokines (p< 0.001, fold change > 10.0). MIP-1 on day 3, IL-13 and Fas-L on day 7, and Fas-L on day 14 were the most significantly downregulated cytokines after intravitreal aflibercept treatment (p< 0.001, fold change > 5.0). M2 polarization and VEGFA genes were significantly increased in the CNV formation, whereas aflibercept suppressed M2 polarization and VEGFA genes. IL-7 was negatively related to the CNV lesion area on day 14 after intravitreal aflibercept treatment (r = −0.938, p = 0.006). Conclusion: The inflammatory cytokines and the M1/M2 macrophage genes significantly changed in the CNV mouse model. This result suggests that inflammatory cytokines and macrophages play a critical role in the physiopathology of CNV.

scholarly journals Effect of Modified Sijunzi Decoction on Macrophage Polarization Into M1 Phenotype in a Balb/c Mouse Model of Breast Cancer

2021 ◽  
Author(s):  
huamiao zhou ◽  
Binyue Xu ◽  
Yong Guo ◽  
Xiangyun Zhang ◽  
Zhendong Liu
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Tumor Metastasis ◽  
Macrophage Polarization ◽  
Cancer Cell Line ◽  
Control Group ◽  
Mouse Breast Cancer ◽  
M1 Phenotype ◽  
The Right

Abstract Background: The five-year survival rate of breast cancer is bleak because of the predilection for bone metastasis. Tumor-associated macrophages are involved in tumor metastasis and are divided into two antagonistic types, M1 and M2. This study aimed to detect the anti-tumor effect of the modified Sijunzi decoction (MSJZD) in a mouse model of breast cancer and explore whether MSJZD inhibited tumor metastasis by regulating macrophage polarization.Materials and methods: A luciferase-expressing mouse breast cancer cell line Luc-4T1 was inoculated into the right mammary fat pad of mice to establish a Balb/c mouse model of breast cancer. After inoculation for 24 h, the mice were randomly divided into the MSJZD group and control group (n = 5 per group). The mice in the MSJZD group were gavaged with 0.77 g/mL MSJZD once daily for 35 days, whereas those in the control group were administered the same volume of normal saline. Subsequently, the effects of MSJZD on tumor growth and macrophage polarization were investigated.Results: On day 35, MSJZD reduced tumor growth in the mouse model of breast cancer. Flow cytometry showed that the M1 marker (inducible nitric oxide synthase+) was increased in the MSJZD group relative to that in the control group, whereas the M2 marker (CD206+) did not exhibit significant differences between the two groups. The results indicated that MSJZD promoted macrophage polarization into the M1 phenotype.Conclusions: Our findings showed that MSJZD promoted macrophage polarization into the M1 phenotype, thus inhibiting tumor growth and metastasis in breast cancer.

scholarly journals MiR-98-5p expression inhibits polarization of macrophages to an M2 phenotype by targeting Trib1 in inflammatory bowel disease

2020 ◽  
Author(s):  
Yunhua Peng ◽  
Qingyuan Wang ◽  
Wei Yang ◽  
Qiqi Yang ◽  
Ynani Pei ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Macrophage Polarization ◽  
Luciferase Reporter ◽  
Marker Genes ◽  
M2 Macrophage ◽  
M1 Macrophage ◽  
Inflammatory Bowel ◽  
M2 Macrophage Polarization ◽  
M2 Phenotype

Herein, we unfolded miR-98-5p mechanism in inflammatory bowel disease (IBD). IBD mouse model was established. The severity of colitis was assessed daily using the disease activity index (DAI). Murine peritoneal macrophages were stimulated by lipopolysaccharide (LPS). MiR-98-5p, tribbles homolog 1 (Trib1), M1 and M2 macrophage marker genes mRNA expression was analyzed. The relationship between miR-98-5p and Trib1 was explored using a luciferase reporter assay. The strategy of loss-of-function was used to explore the mechanism of miR-98-5p in macrophage polarization, inflammation and IBD. The results revealed that IBD mice had higher DAI index and miR-98-5p expression when compared to the Sham group. MiR-98-5p and Trib1 displayed a targeted regulation relationship. Knockdown of miR-98-5p transformed LPS-induced M1 macrophage polarization into M2 macrophage polarization and inhibited inflammation via up-regulating Trib1. However, shTrib1 reversed the effects. In vivo experiment, silencing of miR-98-5p, diminished the DAI and promoted M2 macrophage polarization. In conclusion, knockdown of miR-98-5p changed macrophage polarization to the M2 phenotype by increasing Trib1 expression, thereby alleviating IBD symptoms.

scholarly journals Anti-inflammatory Activity of a Polypeptide Fraction From Achyranthes bidentate in Amyloid β Oligomers Induced Model of Alzheimer’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangyu Ge ◽  
Yitong Wang ◽  
Shu Yu ◽  
Xuemin Cao ◽  
Yicong Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Cytokines ◽  
Mrna Levels ◽  
Bv2 Microglia ◽  
M1 Phenotype ◽  
Anti Inflammatory ◽  
The Brain ◽  
M2 Phenotype ◽  
Pro Inflammatory Cytokines

Neuroinflammation plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and anti-inflammation has been considered as a potential therapeutic strategy. Achyranthes bidentate polypeptide fraction k (ABPPk) was shown to protect neurons from death and suppress microglia and astrocyte activation in PD model mice. However, how ABPPk regulates neuroinflammation to exert a neuroprotective role remains unclear. Toxic Aβ oligomers (AβOs) can trigger inflammatory response and play an important role in the pathogenesis of AD. In the present study, for the first time, we investigated the effects and underlying mechanisms of ABPPk on neuroinflammation in AβOs-induced models of AD. In vitro, ABPPk pretreatment dose-dependently inhibited AβOs-induced pro-inflammatory cytokines mRNA levels in BV2 and primary microglia. ABPPk pretreatment also reduced the neurotoxicity of BV2 microglia-conditioned media on primary hippocampal neurons. Furthermore, ABPPk down-regulated the AβOs-induced phosphorylation of IκBα and NF-κB p65 as well as the expression of NLRP3 in BV2 microglia. In vivo, ABPPk pre-administration significantly improved locomotor activity, alleviated memory deficits, and rescued neuronal degeneration and loss in the hippocampus of AβOs-injected mice. ABPPk inhibited the activation of microglia in hippocampal CA3 region and suppressed the activation of NF-κB as well as the expression of NLRP3, cleaved caspase-1, and ASC in the brain after AβOs injection. ABPPk hindered the release of pro-inflammatory cytokines and promoted the release of anti-inflammatory cytokines in the brain. Notably, the polarization experiment on BV2 microglia demonstrated that ABPPk inhibited M1-phenotype polarization and promoted M2-phenotype polarization by activating the LPS- or AβOs-impaired autophagy in microglia. Taken together, our observations indicate that ABPPk can restore the autophagy of microglia damaged by AβOs, thereby promoting M2-phenotype polarization and inhibiting M1-phenotype polarization, thus playing a role in regulating neuroinflammation and alleviating neurotoxicity.

scholarly journals mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanhui Hao ◽  
Leilei Yang ◽  
Ying Liu ◽  
Yumeng Ye ◽  
Jiayu Wang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization ◽  
Differentially Expressed ◽  
Tissue Formation ◽  
Diabetic Mice ◽  
M1 Macrophage ◽  
Differentially Expressed Mirnas ◽  
Diabetic Wounds ◽  
M2 Phenotype

Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polarization. However, the differentially expressed miRNAs involved in wound healing and their effects on diabetic wounds remain to be further explored. In this study, we first identified differentially expressed miRNAs in the inflammation, tissue formation and reconstruction phases in wound healing using Illumina sequencing and RT-qPCR techniques. Thereafter, the expression of musculus (mmu)-miR-145a-5p (“miR-145a-5p” for short) in excisional wounds of diabetic mice was identified. Finally, expression of miR-145a-5p was measured to determine its effects on macrophage polarization in murine RAW 264.7 macrophage cells and wound healing in diabetic mice. We identified differentially expressed miRNAs at different stages of wound healing, ten of which were further confirmed by RT-qPCR. Expression of miR-145a-5p in diabetic wounds was downregulated during the tissue formation stage. Furthermore, we observed that miR-145a-5p blocked M1 macrophage polarization while promoting M2 phenotype activation in vitro. Administration of miR-145a-5p mimics during initiation of the repair phase significantly accelerated wound healing in db/db diabetic mice. In conclusion, our findings suggest that rectifying macrophage function using miR-145a-5p overexpression accelerates diabetic chronic wound healing.

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