scholarly journals Abnormal Macrophage Polarization in Patients with Myelodysplastic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Gaochao Zhang ◽  
Liyan Yang ◽  
Yu Han ◽  
Haiyue Niu ◽  
Li Yan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Macrophage Polarization ◽  
Control Group ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Tnf Α ◽  
Bone Marrow Microenvironments ◽  
Medical University

Background. This study is aimed at assessing the subsets of bone marrow macrophages in patients with myelodysplastic syndrome (MDS) and exploring the role of macrophages in the pathogenesis of MDS. Methods. Thirty-eight newly diagnosed MDS patients were enrolled in the Department of Hematology of General Hospital of Tianjin Medical University from June 2015 to June 2016. Bone marrow monocytes and macrophage subsets (M1/M2) were detected in patients with MDS and normal controls by flow cytometry. M1 macrophages were cultured in vitro, and the expression of IL-1β and TNF-α mRNA was measured using real-time polymerase chain reaction. Results. Compared with the normal control group, the proportion of bone marrow monocytes was higher ( 2.11 ± 0.93 % vs. 3.66 ± 3.38 % ), and the mean fluorescence intensity of surface molecule CD14 was lower in the higher-risk (HR) MDS group ( 639.05 ± 359.78 vs. 458.26 ± 306.72 , p < 0.05 ). The ratio of M2 macrophages to monocytes was higher in patients with HR-MDS ( 1.82 ± 2.47 % vs. 3.93 ± 3.81 % , p < 0.05 ). The ratio of M1 to M2 macrophages was lower in the HR-MDS group ( 3.50 ± 3.22 vs. 1.80 ± 0.88 , p < 0.05 ). The expression of IL-1β and TNF-α mRNA in M1 macrophages was significantly lower in the MDS group ( p < 0.05 ). Conclusions. Patients with MDS had abnormal macrophage polarization, which may be involved in the alteration of bone marrow microenvironments.

scholarly journals Luteolin Regulates the Differentiation of Regulatory T Cells and Activates IL-10-Dependent Macrophage Polarization against Acute Lung Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ke Xie ◽  
Yu-sen Chai ◽  
Shi-hui Lin ◽  
Fang Xu ◽  
Chuan-jiang Wang
Keyword(s):  
T Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Mononuclear Cells ◽  
Macrophage Polarization ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Treg Differentiation

Objectives. Inflammatory disease characterized by clinical destructive respiratory disorder is called acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Studies have shown that luteolin exerts anti-inflammatory effects by increasing regulatory T cells (Tregs). In this study, we aimed to determine the effects of luteolin on ALI/ARDS and Treg differentiation. Methods. In this paper, we used cecal ligation puncture (CLP) to generate an ALI mouse model to determine the effects of luteolin on ALI/ARDS. Lung tissues were stained for interleukin- (IL-) 17A and myeloperoxidase (MPO) by immunohistochemical analysis. The levels of Treg-related cytokines in serum and bronchoalveolar lavage fluid (BALF) of mice were detected. The protein levels of NF-κB p65 in lung tissues were measured. Macrophage phenotypes in lung tissues were measured using immunofluorescence. The proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells (PBMCs) was quantified. Furthermore, in vitro, we evaluated the effects of luteolin on Treg differentiation, and the effects of IL-10 immune regulation on macrophage polarization were examined. Results. Luteolin alleviated lung injury and suppressed uncontrolled inflammation and downregulated IL-17A, MPO, and NF-κB in the lungs of CLP-induced mouse models. At this time, luteolin upregulated the level of IL-10 in serum and BALF and the frequency of CD4+CD25+FOXP3+ Tregs in PBMCs and splenic mononuclear cells of CLP mice. Luteolin treatment decreased the proportion of M1 macrophages and increased the proportion of M2 macrophages in lungs of CLP-induced mouse models. In vitro, administration of luteolin significantly induced Treg differentiation, and IL-10 promoted the polarization of M2 macrophages but reduced the polarization of M1 macrophages. Conclusions. Luteolin alleviated lung injury and suppressed uncontrolled inflammation by inducing the differentiation of CD4+CD25+FOXP3+ Tregs and upregulating the expression of IL-10. Furthermore, the anti-inflammatory cytokine IL-10 promoted polarization of M2 macrophages in vitro. Luteolin-induced Treg differentiation from naïve CD4+ T cells may be a potential mechanism for regulating IL-10 production.

scholarly journals The effect of macrophage polarization on the expression of the oxytocin signalling system in enteric neurons

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yao Shi ◽  
Shuang Li ◽  
Haojie Zhang ◽  
Jianchun Zhu ◽  
Tongtong Che ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Recovery Phase ◽  
Enteric Neurons ◽  
M1 Macrophages ◽  
Signalling System ◽  
Inflammatory Phase ◽  
Tnf Α ◽  
Colitis Model ◽  
M1 Type

Abstract Background The aim of the current study was to investigate the effect of macrophage polarization on the expression of oxytocin (OT) and the oxytocin receptor (OTR) in enteric neurons. Methods In this study, we used a classic colitis model and D-mannose model to observe the correlation between macrophage polarization and OT signalling system. In order to further demonstrate the effect of macrophages, we examined the expression of OT signalling system after depletion of macrophages. Results The data showed that, in vitro, following polarization of macrophages to the M1 type by LPS, the macrophage supernatant contained proinflammatory cytokines (IL-1β, IL-6 and TNF-α) that inhibited the expression of OT and OTR in cultured enteric neurons; following macrophage polarization to the M2 type by IL4, the macrophage supernatant contained anti-inflammatory cytokines (TGF-β) that promoted the expression of OT and OTR in cultured enteric neurons. Furthermore, M1 macrophages decreased the expression of the OT signalling system mainly through STAT3/NF-κB pathways in cultured enteric neurons; M2 macrophages increased the expression of the OT signalling system mainly through activation of Smad2/3 and inhibition of the expression of Peg3 in cultured enteric neurons. In a colitis model, we demonstrated that macrophages were polarized to the M1 type during the inflammatory phase, with significant decreased in the expression of OT and OTR. When macrophages were polarized to the M2 type during the recovery phase, OT and OTR expression increased significantly. In addition, we found that D-mannose increased the expression of OT and OTR through polarization of macrophages to the M2 type. Conclusions This is the first study to demonstrate that macrophage polarization differentially regulates the expression of OT and OTR in enteric neurons.

scholarly journals 726 Tumor Treating Fields (TTFields) induce an altered polarization program in M1/M2 macrophages

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A756-A756
Author(s):  
Yiftah Barsheshet ◽  
Boris Brant ◽  
Tali Voloshin ◽  
Alexandra Volodin ◽  
Lilach Koren ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Electric Fields ◽  
Bone Marrow Cells ◽  
Macrophage Polarization ◽  
Intermediate Frequency ◽  
M2 Macrophages ◽  
Activation Markers ◽  
Tumor Treating Fields ◽  
Tnf Α ◽  
M1 Phenotype

BackgroundTumor Treating Fields (TTFields) are low intensity (1–3 V/cm), intermediate frequency (100–500 kHz), alternating electric fields, with demonstrated anti-mitotic effects on cancerous cells. TTFields are clinically approved for treatment of patients with glioblastoma and mesothelioma in the US and Europe. The current study aimed to examine the potential of TTFields to polarize unstimulated M0 macrophages and to regulate the phenotypes of M1 and M2 macrophages.MethodsBone marrow–derived macrophages (BMDMs) were generated from bone marrow cells flushed from the femurs and tibias of 5–8-week-old Balb\C mice. Unstimulated (M0 phenotype) BMDMs and BMDMs stimulated with LPS+IFN-γ (M1 polarization) or IL-4 (M2 polarization) were treated with TTFields (150 kHz) for 24 or 48 hours. Surface expression of the macrophage biomarker F4/80 and the activation markers CD80, major histocompatibility complex class II (MHC II), and inducible nitric oxide synthase (iNOS) were examined by flow cytometry. The heterogeneity of the stimulated macrophages was examined by a multiplexed secretion assay, capturing 13 different proteins: CXCL1 (KC), IL-18, IL-23, IL-12p70, IL6, TNF-α, IL-12p40, free active TGF-β1, CCL22 (MDC), IL-10, IL-6, G-CSF, CCL17 (TARC) and IL-1β.ResultsApplication of TTFields to polarized (M1 or M2) or unpolarized BMDMs significantly increase in the percentage of CD80+/MHC IIhigh cells. M1 polarized BMDMs treated with TTFields also displayed elevation of intracellular iNOS levels. Cell supernatants of M1 and M2 stimulated BMDMs, as well as of unstimulated M0 BMDMs, displayed a pro-inflammatory secretion pattern following delivery of TTFields, with increased levels of CXCL1, IL-18, IL-23, IL-12p70, TNF-α, IL-12p40, CCL22, G-CSF, CCL17 and IL-1β.ConclusionsThis research showed that TTFields polarized unstimulated BMDMs to the M1 phenotype, elevated the pro-inflammatory phenotype of M1 polarized BMDMs, and induced phenotype skewing of M2 polarized BMDMs to the M1 phenotype. These results elucidate a novel immunoregulatory role of TTFields on macrophage polarization. Future studies will aim to focus on the mechanism governing this phenotypic skewing.

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 A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

2021 ◽  
Vol 7 ◽  
Author(s):  
Rainer Oberbauer ◽  
Matthias Edinger ◽  
Gabriela Berlakovich ◽  
Peter Kalhs ◽  
Nina Worel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kidney Transplant ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Donor Bone Marrow ◽  
Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR &lt;35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

scholarly journals Altered Expression of Hematopoiesis Regulatory Genes in the Bone Marrow Mesenchymal Stem Cells of Patients of Aplastic Anemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3904-3904
Author(s):  
Soniya Nityanand ◽  
Naresh Kumar Tripathy ◽  
Chandra Prakash Chaturvedi ◽  
Ekta Minocha ◽  
Akhilesh Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Fold Increase ◽  
Regulatory Genes ◽  
Control Group ◽  
Medical Sciences ◽  
Post Graduate ◽  
Tnf Α ◽  
Post Graduate Institute

Abstract Mesenchymal stem cells (MSC) are an important component of the hematopoietic niche in the bone marrow (BM) and regulate hematopoiesis by producing a variety of cytokines and growth factors. In aplastic anemia (AA), most of the studies have attributed the reduced hematopoiesis to a defect in hematopoietic stem cells (HSC) and limited data is available on the role of BM-MSC in AA. Therefore, the objective of the present study was to evaluate the expression of hematopoiesis regulatory genes, viz. granulocyte colony stimulating factor (G-CSF), stromal cell derived factor (SDF-1), stem cell factor (SCF), tumor necrosis factor-alpha (TNF-α) macrophage inflammatory protein-1 alpha (MIP-1α) and transforming growth factor-beta (TGF-β) in BM-MSC of patients with AA and compare it with BM-MSC of control group. Twenty patients of idiopathic acquired AA with a median age of 25.5 years (range: 12-64 years) were included in the study. The control group consisted of 10 healthy volunteers and 10 patients with iron deficiency anemia or immune thrombocytopenic purpura. The median age of the control group was 20 years (range: 11-62 years). The BM-MSC were isolated and cultured as per protocol standardized and previously published by us. Third passage cells were used in the study. The MSC were characterized both by their phenotypic markers and by their ability to differentiate into adipogenic and osteogenic lineages. The expression of hematopoiesis regulatory genes was studied by real-time quantitative polymerase chain reaction (qRT-PCR). The GAPDH was used as the housekeeping gene to normalize the transcript levels and the fold change in the gene expression was calculated by 2-ΔΔCtmethod. The BM-MSC of AA patients and controls had similar morphology and expression of mesenchymal markers CD73, CD105, CD90 and CD166, absence of expression of hematopoietic markers CD13, CD34 and CD45 and of HLA-DR. However, the BM-MSC of AA patients exhibited a higher adipogenic and a lower osteogenic differentiation in comparison to those of controls. Further, the BM-MSC of AA patients in comparison to those of control group, had a higher expression of G-CSF (fold increase: 1.99; p<0.0001), SDF-1 (fold increase: 1.37; p<0.01) and TNF-α (fold increase: 10.68; p<0.0001) and a very low expression of MIP-1α (fold decease: 50.0; p<0.0001) transcripts. The expression of SCF and TGF-β transcripts were comparable in the BM-MSC of both the groups (p>0.05). Though AA patients have been shown to have elevated levels of G-CSF in the peripheral blood and BM but there is only one previous report on G-CSF gene expression in BM-MSC of AA, in which a higher expression was observed and thus corroborates with our data. There is no data available on SDF-1 levels in the peripheral blood and bone marrow of AA patients. We have observed higher gene expression of SDF-1 in BM-MSC of AA patients. The higher expression of G-CSF and SDF-1, pro-hematopoietic factors, in AA may be due to a compensatory response of the BM stroma to boost the hematopoiesis. Our observation of higher TNF-α gene expression in BM-MSC corroborates with previous reports on higher levels of this anti-hematopoietic cytokine in the BM plasma of patients with AA and indicates that MSC could contribute to the increase in the TNF-α level in the BM of AA patients. A conspicuous observation of our study was a markedly decreased expression of MIP-1α gene in BM-MSC of AA and to the best of our knowledge this is the first report on MIP-1α in AA. MIP-1α is a chemokine which has been shown to inhibit proliferation of HSC in vitro and thus may help to maintain HSC in an undifferentiated state. Furthermore, MIP-1α has also been reported to mediate interaction of HSC with stromal cells in BM and may have a role in supporting hematopoiesis. Its precise role in AA needs to be studied further. We are currently studying the levels of these cytokines/growth factors in the BM plasma of the same cohort of AA patients and controls and the data will be presented. Our study thus shows that BM-MSC of AA patients have altered expression of hematopoiesis regulatory genes which may contribute to the pathobiology of the disease. Disclosures Nityanand: Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment, Research Funding. Tripathy:Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment. Chaturvedi:Dept of Biotechnology, Govt of India: Employment. Minocha:Dept of Science and Technology, Govt of India: Other: PhD scholarship. Sharma:Sanjay Gandhi Post Graduate Institute of Medical Sciences: Employment. Rahman:SGPGI, Lucknow , India: Employment, Research Funding.

Functional characteristics of PMJ2-R macrophages

2020 ◽  
Vol 18 (4) ◽  
pp. 133-137
Author(s):  
P.M. Kozhin ◽  
◽  
A.L. Rusanov ◽  
O.O. Shoshina ◽  
N.G. Luzgina ◽  
...  
Keyword(s):  
Cell Biology ◽  
Alternative Pathway ◽  
Peritoneal Macrophages ◽  
Alternative Activation ◽  
M2 Macrophages ◽  
Phagocytic Cells ◽  
Phenotypic Properties ◽  
M1 Macrophages ◽  
Oxidized Dextran ◽  
Tnf Α

Objective. To evaluate the ability of PMJ2-R cells for classical and alternative activation and to assess the effect of oxidized dextran on the functional status of polarized cells of this line. OD is a promising lysosomotropic agent used for targeted drug delivery to phagocytic cells. Materials and methods. We analyzed ability of immortalized murine peritoneal macrophages PMJ2R (ATCC CRL2458) to classical and alternative polarization, including that upon exposure to OD. We used real-time polymerase chain reaction to assess gene expression of competing arginine pathways. The capacity of phagocytes to engulf zymosan granules was evaluated using fluorescence microscopy. Results. We observed metabolic changes in PMJ2-R cells following their classical and alternative activation; these changes were typical of M1 and M2 macrophages, respectively. M1 macrophages demonstrated most active phagocytosis, while the activity of phagocytosis in M2 macrophages increased dose-dependently upon AD exposure. OD upregulates production of proinflammatory cytokine TNF-α in intact PMJ2-R cells and M1 macrophages. Conclusion. PMJ2-R cells have the capacity to phagocytose particles, can be polarized via the classical and alternative pathway, can modulate their functional activity in response to OD (a macrophagotropic substance), and exhibit the main phenotypic properties typical of peritoneal macrophages from C57Bl/6J mice. Therefore, cells of this line can be used as model cells in the investigation of phagocytic cell biology and pathology. Key words: alternative activation, classical activation, oxidized dextran, peritoneal macrophages, phagocytosis, C57Bl/6J, PMJ2-R

Abstract 660: Macrophage Specific Deficiency of the Transient Receptor Potential Canonical 3 Channel Reduces Apoptosis and Necrosis in Advanced Atherosclerotic Plaques

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sumeet A Solanki ◽  
Guillermo Vazquez
Keyword(s):  
Bone Marrow ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Atherosclerotic Plaques ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Transient Receptor Potential Canonical ◽  
Transient Receptor ◽  
Apoptosis And Necrosis

Background: Macrophage apoptosis plays a critical role in progression of atherosclerosis. Previous studies suggest that M1 and M2 macrophage phenotypes dominate atherosclerosis. Recently, we showed that advanced lesions in the aortic root of Apoe -/- mice transplanted with bone marrow deficient in the calcium-permeable channel Transient Receptor Potential Canonical 3 (TRPC3) are characterized by reduced areas of necrosis and less apoptotic macrophages. However, the donor mice used in these studies had global deficiency of TRPC3, raising the question whether the observed phenotype was also contributed by TRPC3-deficient non-myeloid cells which could undermine the true impact of macrophage deletion of TRPC3. To address this important question, we generated mice with macrophage-specific loss of TRPC3 function (MacTrpc3 -/- ). Methods & results: 13 six week-old female Ldlr -/- mice were irradiated and transplanted with Ldlr -/- (control) or MacTrpc3 -/- Ldlr -/- (experimental) bone marrow and kept on high fat diet for 14 weeks. At the end of the diet period, aortic roots were sectioned and processed for atherosclerotic lesion analysis. Total lesion size (H&E), neutral lipid (Oil Red O) and macrophage content (CD68 staining) were not different between groups. However, we found a 1.7 fold decrease (P=0.01) in percent necrotic area in advanced lesions of MacTrpc3 -/- Ldlr -/- mice (23.12 ± 2.07%, n=10) compared to controls (39.63 ± 5.93%, n=10). Using in situ TUNEL we found that MacTrpc3 -/- Ldlr -/- lesions have less apoptotic cells compared to controls, and these overlapped with CD68 + areas. Using iNOS and mannose receptor as markers for M1 and M2 macrophages, respectively, we found that both subsets overlapped with CD68 + and TUNEL + positive areas, with no differences between groups (n=5). Previously, we showed that M1, but not M2 macrophages derived from MacTrpc3 -/- mice, had reduced apoptosis. This suggests that reduced plaque necrosis of MacTrpc3 -/- Ldlr -/- mice may be due to reduced apoptosis of M1 macrophages. In sum, these in vivo studies indicate that macrophage-specific deficiency of TRPC3 has a genuine beneficial effect on advanced atherosclerotic plaques, reducing apoptosis and necrosis, probably due to a selective effect of TRPC3 on M1 macrophages.

Study on mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia

2020 ◽  
Author(s):  
qiong Ning ◽  
xiangxin li ◽  
Xiangdong Jian ◽  
Xiaopeng He
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Immune Escape ◽  
Serum Levels ◽  
Control Group ◽  
M2 Macrophages ◽  
Experimental Group ◽  
Group Serum ◽  
Acute Myeloid

Abstract To study the mechanism of Tim-3 on immune escape in benzene-induced acute myeloid leukemia (AML), to provide potential targets of clinical monitoring and intervention of hematological toxicity in benzene-induced AML . C3H/He mice were randomly divided into control group and experimental group. Serum levels of IL-12 in the experimental group were significantly lower than that in the control group. Serum levels of TGF-β1 in the experimental group were significantly higher than that in the control group( p <0.05). The proportion of Tim-3 positive CD14 + monocytes of bone marrow and spleen in the experimental group were both significantly higher than that in the control group ( p <0.05) by Flow cytometry (FCM). Compared with the control group, the expression of Tim-3 on (M1+M2) macrophages of bone marrow in the experimental group significantly increased by immunofluorescence assay. The expression of type M2 macrophages in (M1+M2) macrophages of bone marrow and spleen tissues in the experimental group were both higher than that in the control group. The expression levels of p-PI3K, p-AKT and p-mTOR in the experimental group were all significantly higher than that in the control group. Tim-3 was highly expressed in macrophages in benzene-induced AML. It promoted the activation of PI3K/AKT/mTOR signaling pathway, stimulated the secretion of anti-inflammatory cytokines, and inhibited the secretion of pro-inflammatory cytokines. High expression of Tim-3 changed the phenotype and function of macrophages by promoting the macrophages polarization, thus inducing negative immune response in the tumor microenvironment and tumor immune escape.

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