scholarly journals Downregulation of EZH2 in Trophoblasts Induces Decidual M1 Macrophage Polarization: a Potential Cause of Recurrent Spontaneous Abortion

2021 ◽  
Author(s):  
Ye Shang ◽  
Shujuan Wu ◽  
SaiJiao Li ◽  
Xiaolin Qin ◽  
Jiao Chen ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Close Contact ◽  
Macrophage Polarization ◽  
Regulatory Gene ◽  
Active Role ◽  
Recurrent Spontaneous Abortion ◽  
Healthy Controls ◽  
Immune Functions ◽  
M1 Macrophage ◽  
And Function

AbstractMacrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal–fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy‐related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP‐1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss.

scholarly journals MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization

2020 ◽  
Vol 16 (12) ◽  
pp. 2248-2264 ◽  
Author(s):  
Xiaoxiao Zhu ◽  
Haiping Liu ◽  
Zhen Zhang ◽  
Ran Wei ◽  
Xianbin Zhou ◽  
...  
Keyword(s):  
Spontaneous Abortion ◽  
Macrophage Polarization ◽  
Recurrent Spontaneous Abortion ◽  
M1 Macrophage

scholarly journals Activated γδ T Cells With Higher CD107a Expression and Inflammatory Potential During Early Pregnancy in Patients With Recurrent Spontaneous Abortion

2021 ◽  
Vol 12 ◽  
Author(s):  
Long Yu ◽  
Yang Zhang ◽  
Jinfeng Xiong ◽  
Jianjun Liu ◽  
Ying Zha ◽  
...  
Keyword(s):  
T Cells ◽  
Spontaneous Abortion ◽  
Healthy Subjects ◽  
Γδ T Cells ◽  
Transcriptional Analysis ◽  
Recurrent Spontaneous Abortion ◽  
Healthy Controls ◽  
Protective Effects ◽  
Inflammatory Microenvironment

Previous studies have reported the involvement of γδ T cells in recurrent spontaneous abortion (RSA); however, both pathogenic and protective effects were suggested. To interrogate the role of γδ T cells in RSA, peripheral blood from RSA patients and healthy women with or without pregnancy were analyzed for γδ T cells by flow cytometry (n = 9–11 for each group). Moreover, the decidua from pregnant RSA patients and healthy controls (RSA-P and HC-P group, respectively) was simultaneously stained for γδ T cells by immunohistochemistry (IHC) and bulk sequenced for gene expression. Our results demonstrated that the frequencies of peripheral γδ T cells and their subpopulations in RSA patients were comparable to that in healthy subjects, but the PD1 expression on Vδ2+ cells was increased in pregnant patients. Furthermore, peripheral Vδ2+ cells in RSA-P patients demonstrated significantly increased expression of CD107a, as compared to that in pregnant healthy controls. In addition, RSA-P patients had higher proportion of IL-17A-secreting but not IL-4-secreting Vδ2+ cells compared to the control groups. In decidua, an inflammatory microenvironment was also evident in RSA-P patients, in which CCL8 expression and the infiltration of certain immune cells were higher than that in the HC-P group, as revealed by transcriptional analysis. Finally, although the presence of γδ T cells in decidua could be detected during pregnancy in both RSA patients and healthy subjects by multicolor IHC analysis, the expression of CD107a on γδ T cells was markedly higher in the RSA-P group. Collectively, our results indicated that the increased activation, cytotoxicity, and inflammatory potential of peripheral and/or local γδ T cells might be responsible for the pathogenesis of RSA. These findings could provide a better understanding of the role of γδ T cells in RSA and shed light on novel treatment strategies by targeting γδ T cells for RSA patients.

An interaction between Scribble and the NADPH oxidase complex controls M1 macrophage polarization and function

2016 ◽  
Vol 18 (11) ◽  
pp. 1244-1252 ◽  
Author(s):  
Weiyue Zheng ◽  
Masataka Umitsu ◽  
Ishaan Jagan ◽  
Charles W. Tran ◽  
Noboru Ishiyama ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Macrophage Polarization ◽  
M1 Macrophage ◽  
Nadph Oxidase Complex ◽  
And Function

Combating HIV-1 by Targeting Drug Efflux Transporters on the Macrophage Reservoir

2021 ◽  
Author(s):  
◽  
Ying Mu ◽  
Keyword(s):  
Viral Suppression ◽  
Macrophage Polarization ◽  
Antiretroviral Drugs ◽  
Efflux Transporters ◽  
Drug Efflux ◽  
M1 Macrophage ◽  
And Function ◽  
Hiv 1 ◽  
Transporter Expression ◽  
Drug Efflux Transporters

Introduction. HIV-1 eradication has not been achieved so far due to the existence of the cellular reservoir in which the virus can reside and replicate even under antiretroviral drug therapy (ART). Infected macrophages, which represent a long-term viral reservoir have been shown to lead to viral rebound independently. In response to the environmental stimuli, macrophages can be polarized into different phenotypes: the pro-inflammatory M1 and the anti-inflammatory M2. Tobacco smoking and alcohol drinking, which are prevalent among people who are living with HIV-1, have been shown to promote HIV-1 progression and decrease the efficacy of antiretroviral drugs. A commonly used macrolide antibiotic azithromycin (AZM) has been shown to shift macrophage polarization in a murine macrophage cell line. In the previous research, we found that drug efflux transporters expressed differently between macrophage phenotypes. In this dissertation, we examined the effects of CSC, ethanol exposure, and AZM on the expression and function of clinically relevant drug efflux transporters, viral suppression of antiretroviral drugs, and macrophage polarization. Methods. The human monocytic cell lines U937 and the U1 cell line, which is derived from HIV-1 infected U937, were used and polarized to the M1 and M2 macrophages. Cells with the treatment of CSC, ethanol, and AZM were harvested for downstream analysis including macrophage polarization, oxidative stress, cytokine production, transporter expression and function, and viral suppression. Cells treated with IKK-16, an inhibitor of the NF-κB signaling pathway, were harvested for the analysis of transporter expression and function. Protease inhibitor lopinavir (LPV) was used to suppress viral replication and the intracellular LPV was measured using LC-MS/MS. Results. Cigarette smoke condensate (CSC) and AZM shifted M1 macrophage polarization to M2 while having minimal effects on the M2 macrophage polarization. Inhibiting macrophage subset-specific transporters significantly increased intracellular antiretroviral drug (ARV) concentrations and drug efficacy. Neither CSC nor ethanol had any effect on the transporter inhibition-mediated viral reduction. AZM modulated the expression of major drug efflux transporters in both macrophage subsets and increased intracellular ARV concentration in M2 macrophages. NF-κB and JNK are involved in the M1 macrophage polarization shift and NF-κB was also shown to regulate major transporter expression. Conclusion. Modulating the expression and function of macrophage subset-specific transporter expression can increase intracellular ARV concentration and drug efficacy of viral suppression. Targeting subset-specific transporter may be an effective way to increase intracellular ARV concentration in the macrophage reservoir.

scholarly journals Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

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