scholarly journals ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1724
Author(s):  
Phetcharawan Lye ◽  
Caroline E. Dunk ◽  
Jianhong Zhang ◽  
Yanxing Wei ◽  
Jittanan Nakpu ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Immune Cells ◽  
Protein A ◽  
Extravillous Trophoblast ◽  
M2 Macrophage ◽  
Maternal Circulation ◽  
M1 Macrophage ◽  
Ccl2 Mrna ◽  
Peripheral Immune Cells

COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (n = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women (n = 6). Second trimester placental explants (16–20 weeks, n = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased ACE2 and CCL2 mRNA expression (p < 0.05). LPS increased cytokine and ACE2 mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta (p < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.

scholarly journals SARS-CoV-2 cell entry gene ACE2 expression in immune cells that infiltrate the placenta in infection-associated preterm birth

2020 ◽  
Author(s):  
Phatcharawan Lye ◽  
Caroline Dunk ◽  
Jianhong Zhang ◽  
Yanxing Wei ◽  
Jittanan Nakpu ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Blood Vessels ◽  
Immune Cells ◽  
Neonatal Infection ◽  
Cell Entry ◽  
M2 Macrophage ◽  
Fetal Blood ◽  
M1 Macrophage ◽  
Acute Increase ◽  
Peripheral Immune Cells

COVID-19 infection during pregnancy is associated with an increased incidence of preterm birth but neonatal infection is rare. We assessed pathways by which SARS-CoV-2 could access the placenta and contribute to fetal transmission. Placentas from pregnancies complicated with chorioamnionitis (ChA), exhibited increased expression of ACE2 mRNA. Treatment of 2nd trimester placental explants with LPS, induced an acute increase in cytokine expression followed by ACE2 mRNA. Placental ACE2 protein localized to syncytiotrophoblast, in fetal blood vessels and M1/M2 macrophage and neutrophils within the villous stroma. Increased numbers of M1 macrophage and neutrophils were present in the placenta of ChA pregnancies. Maternal peripheral immune cells (mainly granulocytes and monocytes) express the ACE2 mRNA and protein. These data suggest that in COVID19 positive pregnancies complicated by ChA, ACE2 positive immune cells have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.

scholarly journals O9 M1 macrophages evoke an increase in PIGR expression in MDA-MB468 breast cancer cells through interlukin-1β

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
W Asanprakit ◽  
D N Lobo ◽  
O Eremin ◽  
A J Bennett
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Immune Cells ◽  
Breast Cancer Cells ◽  
Polarization State ◽  
M2 Macrophage ◽  
M1 Macrophages ◽  
M1 Macrophage ◽  
Macrophage Cytokine

Abstract Introduction The polymeric immunoglobulin receptor (PIGR) is a transmembrane protein, which transports polymeric immunoglobulin (pIg) across the epithelial cells. High expression of PIGR in breast cancer has been reported to associate with increased 5-year survival rate. In this study, the factors in tumour microenvironment which affected PIGR expression in breast cancer cell lines, were investigated. Method M1, M2 macrophage conditioned media (CM) and recombinant human cytokines were used to determine factors which increased PIGR expression in breast cancer cells. The level of PIGR expression in the cells and secreted PIGR free secretory component (SC) were evaluated by real time quantitative polymerase chain reaction and Western blotting. Results M1 macrophage CM induced a striking dose dependent increase in PIGR mRNA expression in MDA-MB468 cells, up to 20-fold in 100% CM. Interferon gamma (IFNγ) and interleukin (IL)-1β also increased PIGR expression in MDA-MB468 cells. However, IL-1β was demonstrated to increase in M1 macrophages, while IFNγ was not. The role of IL-1β secreted from M1 macrophages in increasing expression of PIGR was confirmed by IL-1 receptor blockade, indicating that IL-1β was the M1 macrophage cytokine that enhanced PIGR expression in breast cancer cells. Conclusions IL-1β was the M1 macrophage cytokine which enhanced PIGR expression in breast cancer cells. IFNγ was also shown to increase PIGR expression in the present study. These imply that elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells. Take-home Message IL-1β secreted from M1 macrophage enhances PIGR expression in breast cancer cells. The elevated PIGR expression in breast cancer in vivo may reflect the polarization state of tumour associated immune cells.

scholarly journals PREGNANCY RELATED PLASMA PROTEIN–A AND PREMATURE BIRTH

2021 ◽  
Vol 19 (2) ◽  
pp. 172-177
Author(s):  
Iv. Todorov ◽  
N. Tododrov ◽  
M. Angelova ◽  
K. Peeva
Keyword(s):  
Preterm Birth ◽  
Pregnant Women ◽  
Plasma Protein ◽  
Premature Birth ◽  
Chromosomal Abnormalities ◽  
Placenta Previa ◽  
Protein A ◽  
Preterm Births ◽  
Sonographic Examination ◽  
Increased Risk

Introduction: Children born prematurely are at higher risk of mortality, morbidity, and impaired motor and cognitive development in childhood than prematurely born babies. Aim: To establish the relationship between the corresponding levels of pregnancy-related plasma protein-A (PAPP-A) and the frequency of premature birth. Materials and methods: The study is prospective. The data was collected through monitoring patients through a questionnaire and sonographic examination at 11-13 gestational weeks. The study excluded all known risk factors for preterm birth, such as previous preterm births, pregnant women with gestational diabetes, preeclampsia, hypertension, placenta previa, hydramnion, multiple pregnancies, smoking, structural and chromosomal abnormalities of the fetus and planned preterm birth. The data from the measured values of PAPP-A and the frequency of premature birth in 636 pregnant women were analyzed. Conclusions: PAPP-A levels are a statistically significant factor for preterm birth. It is expected with a 95% probability in the population with PAPP-A values below 0,515 that the cases with premature birth will be from 7 to 14 times more. Pregnant women with PAPP-A level less than 10th per cent are significantly associated with an increased risk of preterm birth.

Advanced Maternal Age and Adverse Maternal and Neonatal Outcomes in Pregnant Women

2020 ◽  
Vol 16 ◽  
Author(s):  
Reza Omani-Samani ◽  
Saman Maroufizadeh ◽  
Nafise Saedi ◽  
Nasim Shokouhi ◽  
Arezoo Esmailzadeh ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Birth ◽  
Low Birth Weight ◽  
Cesarean Section ◽  
Pregnant Women ◽  
Maternal Age ◽  
Unwanted Pregnancy ◽  
Advanced Maternal Age ◽  
Neonatal Outcomes ◽  
Maternal And Neonatal Outcomes

Background: Advanced maternal age is an important predictor for maternal and neonatal outcomes such as maternal mortality, low birth weight, stillbirth, preterm birth, cesarean section and preeclampsia. Objective: To determine the association of advanced maternal age and adverse maternal and neonatal outcomes in Iranian pregnant women. Methods: In this hospital-based cross-sectional study, 5117 pregnant women from 103 hospitals in Tehran, Iran, were participated in the study in 2015. The required data were gathered from hospitals which equipped to the department of obstetrics and gynecology. Advanced maternal age was considered as an independent variable and unwanted pregnancy, preeclampsia, preterm birth, cesarean section and low birth weight were considered as interested outcomes. Results: In our study, the prevalence of advanced maternal age was 12.08%. Advanced maternal age was significantly associated with higher risk of unwanted pregnancy (OR: 1.39, 95% CI: 1.12-1.73), preterm birth (OR: 1.75, 95% CI: 1.28- 2.39) and cesarean section (OR: 1.34, 95% CI: 1.03-1.74). In our study, there was no significant relationship between advanced maternal age and preeclampsia but this relationship could be clinically important (OR: 1.48, 95% CI: 0.99-2.20, P=0.052), and there is no significant relationship between advanced maternal age and low birth weight (OR: 1.08, 95% CI: 0.67-1.74, P=0.736). Conclusion: Advanced maternal age is associated with higher risk of unintended pregnancy, preterm birth and cesarean section but our findings did not support advanced maternal age as a risk factor associated with low birth weight.

scholarly journals FOXE1-Dependent Regulation of Macrophage Chemotaxis by Thyroid Cells In Vitro and In Vivo

2021 ◽  
Vol 22 (14) ◽  
pp. 7666
Author(s):  
Sara C. Credendino ◽  
Marta De Menna ◽  
Irene Cantone ◽  
Carmen Moccia ◽  
Matteo Esposito ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Immune Cells ◽  
Cancer Susceptibility ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
Thyroid Cells ◽  
Transcriptional Alterations ◽  
Cancer Phenotypes

Forkhead box E1 (FOXE1) is a lineage-restricted transcription factor involved in thyroid cancer susceptibility. Cancer-associated polymorphisms map in regulatory regions, thus affecting the extent of gene expression. We have recently shown that genetic reduction of FOXE1 dosage modifies multiple thyroid cancer phenotypes. To identify relevant effectors playing roles in thyroid cancer development, here we analyse FOXE1-induced transcriptional alterations in thyroid cells that do not express endogenous FOXE1. Expression of FOXE1 elicits cell migration, while transcriptome analysis reveals that several immune cells-related categories are highly enriched in differentially expressed genes, including several upregulated chemokines involved in macrophage recruitment. Accordingly, FOXE1-expressing cells induce chemotaxis of co-cultured monocytes. We then asked if FOXE1 was able to regulate macrophage infiltration in thyroid cancers in vivo by using a mouse model of cancer, either wild type or with only one functional FOXE1 allele. Expression of the same set of chemokines directly correlates with FOXE1 dosage, and pro-tumourigenic M2 macrophage infiltration is decreased in tumours with reduced FOXE1. These data establish a novel link between FOXE1 and macrophages recruitment in the thyroid cancer microenvironment, highlighting an unsuspected function of this gene in the crosstalk between neoplastic and immune cells that shape tumour development and progression.

scholarly journals HMGA1 Is a Potential Driver of Preeclampsia Pathogenesis by Interference with Extravillous Trophoblasts Invasion

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 822
Author(s):  
Keiichi Matsubara ◽  
Yuko Matsubara ◽  
Yuka Uchikura ◽  
Katsuko Takagi ◽  
Akiko Yano ◽  
...  
Keyword(s):  
Protein A ◽  
High Mobility ◽  
Extravillous Trophoblast ◽  
High Mobility Group Protein ◽  
Successful Pregnancy ◽  
Group Protein ◽  
Serious Disease ◽  
Proliferation And Invasion ◽  
Extravillous Trophoblasts ◽  
Fertilized Egg

Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure–derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals The PROMISES study: a mixed methods approach to explore the acceptability of salivary progesterone testing for preterm birth risk among pregnant women and trained frontline healthcare workers in rural India

BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e040268
Author(s):  
Danielle Ashworth ◽  
Pankhuri Sharma ◽  
Sergio A Silverio ◽  
Simi Khan ◽  
Nishtha Kathuria ◽  
...  
Keyword(s):  
Mixed Methods ◽  
Preterm Birth ◽  
Pregnant Women ◽  
Barriers And Facilitators ◽  
Rural India ◽  
Structured Interviews ◽  
Framework Analysis ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Thematic Framework

IntroductionIndia has an overall neonatal mortality rate of 28/1000 live births, with higher rates in rural India. Approximately 3.5 million pregnancies in India are affected by preterm birth (PTB) annually and contribute to approximately a quarter of PTBs globally. Embedded within the PROMISES study (which aims to validate a low-cost salivary progesterone test for early detection of PTB risk), we present a mixed methods explanatory sequential feasibility substudy of the salivary progesterone test.MethodsA pretraining and post-training questionnaire to assess Accredited Social Health Activists (ASHAs) (n=201) knowledge and experience of PTB and salivary progesterone sampling was analysed using the McNemar test. Descriptive statistics for a cross-sectional survey of pregnant women (n=400) are presented in which the acceptability of this test for pregnant women is assessed. Structured interviews were undertaken with ASHAs (n=10) and pregnant women (n=9), and were analysed using thematic framework analysis to explore the barriers and facilitators influencing the use of this test in rural India.ResultsBefore training, ASHAs’ knowledge of PTB (including risk factors, causes, postnatal support and testing) was very limited. After the training programme, there was a significant improvement in the ASHAs’ knowledge of PTB. All 400 women reported the salivary test was acceptable with the majority finding it easy but not quick or better than drawing blood. For the qualitative aspects of the study, analysis of interview data with ASHAs and women, our thematic framework comprised of three main areas: implementation of intervention; networks of influence and access to healthcare. Qualitative data were stratified and presented as barriers and facilitators.ConclusionThis study suggests support for ongoing investigations validating PTB testing using salivary progesterone in rural settings.

scholarly journals The Combined Effects of Fine Particulate Matter and Temperature on Preterm Birth in Seoul, 2010–2016

2021 ◽  
Vol 18 (4) ◽  
pp. 1463
Author(s):  
Youngrin Kwag ◽  
Min-ho Kim ◽  
Shinhee Ye ◽  
Jongmin Oh ◽  
Gyeyoon Yim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Preterm Birth ◽  
Pregnant Women ◽  
Low Temperatures ◽  
Fine Particulate Matter ◽  
Temperature Data ◽  
Fine Particulate ◽  
The Mean ◽  
Pm2.5 Exposure ◽  
Pm2.5 Concentration

Background: Preterm birth contributes to the morbidity and mortality of newborns and infants. Recent studies have shown that maternal exposure to particulate matter and extreme temperatures results in immune dysfunction, which can induce preterm birth. This study aimed to evaluate the association between fine particulate matter (PM2.5) exposure, temperature, and preterm birth in Seoul, Republic of Korea. Methods: We used 2010–2016 birth data from Seoul, obtained from the Korea National Statistical Office Microdata. PM2.5 concentration data from Seoul were generated through the Community Multiscale Air Quality (CMAQ) model. Seoul temperature data were collected from the Korea Meteorological Administration (KMA). The exposure period of PM2.5 and temperature were divided into the first (TR1), second (TR2), and third (TR3) trimesters of pregnancy. The mean PM2.5 concentration was used in units of ×10 µg/m3 and the mean temperature was divided into four categories based on quartiles. Logistic regression analyses were performed to evaluate the association between PM2.5 exposure and preterm birth, as well as the combined effects of PM2.5 exposure and temperature on preterm birth. Result: In a model that includes three trimesters of PM2.5 and temperature data as exposures, which assumes an interaction between PM2.5 and temperature in each trimester, the risk of preterm birth was positively associated with TR1 PM2.5 exposure among pregnant women exposed to relatively low mean temperatures (<3.4 °C) during TR1 (OR 1.134, 95% CI 1.061–1.213, p < 0.001). Conclusions: When we assumed the interaction between PM2.5 exposure and temperature exposure, PM2.5 exposure during TR1 increased the risk of preterm birth among pregnant women exposed to low temperatures during TR1. Pregnant women should be aware of the risk associated with combined exposure to particulate matter and low temperatures during TR1 to prevent preterm birth.

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