Chemokines Profiling of Patients with Preterm Birth

Laudański, Piotr; Lemancewicz, Adam; Kuć, Paweł; Charkiewicz, Karol; Ramotowska, Barbara; Krętowska, Małgorzata; Jasińska, Elwira; Raba, Grzegorz; Karwasik-Kajszczarek, Katarzyna; Kraczkowski, J; Laudański, T

doi:10.1155/2014/185758

Cited by 35 publications

(30 citation statements)

References 22 publications

(24 reference statements)

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“…The precise role of CCL22 in human pregnancy is unknown, but maternal cells express CCL22 at low levels throughout pregnancy, with increased levels associated with miscarriage (12). Moreover, the induction of chemokines, including CCL22 and CCL17, are associated with preterm birth in humans (30) and in small animal models (31). The precise role played by CCL22 during T. gondii vertical transmission remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Human placental syncytiotrophoblasts restrict Toxoplasma gondii vertical transmission at two distinct stages and induce CCL22 in response to infection

Ander

Rudzki

Arora

et al. 2017

Preprint

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52Toxoplasma gondii is a major source of congenital disease worldwide, but the cellular and 53 molecular factors associated with its vertical transmission are largely unknown. In humans, the 54 placenta forms the key interface between the maternal and fetal compartments and forms the 55 primary barrier that restricts the hematogenous spread of microorganisms. Here, we utilized 56 primary human trophoblast (PHT) cells isolated from full-term placentas and human mid-gestation 57 chorionic villous explants to determine the mechanisms by which human trophoblasts restrict and 58 respond to T. gondii infection. We show that placental syncytiotrophoblasts, multinucleated cells 59 that are in direct contact with maternal blood, restrict T. gondii infection at distinct stages of the 60 parasite lytic cycle-at the time of attachment and also during intracellular replication. Utilizing 61 comparative RNAseq transcriptional profiling, we also show that human placental trophoblasts at 62 both mid-and late-stages of gestation induce the chemokine CCL22 in response to T. gondii 63 infection, which relies on the secretion of parasite effector(s). Collectively, our findings provide 64 new insights into the mechanisms by which the human placenta restricts the vertical transmission 65 of T. gondii at early and late stages of human pregnancy, and demonstrate the existence of at 66 least two interferon-independent pathways that restrict T. gondii access to the fetal compartment. 67 68 Significance statement 69 Toxoplasma gondii is a major source of congenital disease worldwide and must breach the 70 placental barrier to be transmitted from maternal blood to the developing fetus. The events 71 associated with the vertical transmission of T. gondii are largely unknown. Here, we show that 72 primary human syncytiotrophoblasts, the fetal-derived cells that comprise the primary placental 73 barrier, restrict T. gondii infection at two distinct stages of the parasite life cycle and respond to 74 infection through the induction of the chemokine CCL22. Collectively, our findings provide 75 important insights into the mechanisms by which human syncytiotrophoblasts restrict T. 76 3 gondii infection at early and late stages of human pregnancy and identify the placental-77 enriched signaling pathways induced in response to infection. Toxoplasma gondii is a major source of congenital disease, with ~200,000 global cases 104 of congenital toxoplasmosis reported each year (1). In the majority of instances (~80%), in utero 105 infections by T. gondii result in a range of severe birth defects, including ocular disease and 106 developmental delays, and can also result in fetal death (2). However, despite the clear impact of 107 T. gondii infections on fetal health, the mechanisms by which the parasite is transmitted from the 108 maternal bloodstream into the fetal compartment are largely unknown. 109In eutherian organisms, the placenta serves as the sole source of gas, nutrient, and waste 110 exchange from the fetal compartment and acts as a key barrie...

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Section: Discussionmentioning

confidence: 99%

Human placental syncytiotrophoblasts restrict Toxoplasma gondii vertical transmission at two distinct stages and induce CCL22 in response to infection

Ander

Rudzki

Arora

et al. 2017

Preprint

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“…To assess the concentrations of angiogenic factors in the amniotic fluid, we used a multiplex method [9,11] allowing for the simultaneous determination of 60 proteins per sample. Like a traditional sandwich-based ELISA, it uses a pair of specific protein antibodies for detection.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, the status of selected cytokines in amniotic fluid from chromosomally abnormal pregnancies has already been described [10,11]. There are different sphingolipid concentrations in the amniotic fluid from pregnancies with DS compared with pregnancies with a normal karyotype.…”

Section: Down Syndrome · Angiogenic Factors · Inflammatory Factors · mentioning

confidence: 99%

Amniotic Fluid Angiogenic and Inflammatory Factor Profiling in Foetal Down Syndrome

Zbucka-Krętowska

Charkiewicz²,

Czerniecki³

et al. 2017

Fetal Diagn Ther

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Objectives: Angiogenic factors are proteins that can potentially be related to certain foetal chromosomal abnormalities. The goal of this study was to determine the concentrations of 60 angiogenic factors in the amniotic fluid of women carrying foetuses with Down syndrome (DS). Methods: After analysis of the karyotyping results, for the purpose of this study, we chose 12 women with foetal DS. For the control group, we selected 12 healthy patients with uncomplicated pregnancies (15-18 weeks of gestation) who delivered healthy newborns at term. To assess the concentrations of proteins in the amniotic fluid, we used a protein macroarray, which enabled the simultaneous determination of 60 angiogenic factors per sample. Results: In the amniotic fluid of women with foetal DS compared to patients with healthy foetuses, we reported significant decreases in the concentrations of 14 angiogenic factors, including leptin, angiopoietin 1 (ANG-1), angiostatin, epidermal growth factor (EGF), interleukin 1-beta (IL-1b), interleukin 4 (IL-4), interleukin 12p40 (IL-12p40), monocyte chemotactic protein 2 (MCP-2), matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-9 (MMP-9), platelet endothelial cell adhesion molecule 1 (PECAM-1), transforming growth factor alpha (TGF alpha), vascular endothelial growth factor 2 (VEGFR2), and vascular endothelial growth factor 3 (VEGFR3). Conclusions: Based on our findings, we hypothesise that angiogenic factors may play roles in the pathogenesis of DS. Defining the factors' potential as biochemical factors of DS requires further investigation in a larger group of patients.

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“…Many efforts have been made to try and provide solutions to preterm birth (PTB), but efficacious therapy for the treatment and prevention of PTB are still lacking [4] . The difficulties involved in obtaining preventive measures and effective treatment for PTB is due to the heterogeneity of confounders involved in the initiation of uterine contraction and PTB [3,5] . A previous research has focused more on the extremely and very PTB due to the large clinical problems associated to this gestational age group [3][4][5] .…”

Section: Introductionmentioning

confidence: 99%

“…The difficulties involved in obtaining preventive measures and effective treatment for PTB is due to the heterogeneity of confounders involved in the initiation of uterine contraction and PTB [3,5] . A previous research has focused more on the extremely and very PTB due to the large clinical problems associated to this gestational age group [3][4][5] . A noninvasive approach to assess protein biomarkers in predicting PTB is crucial as invasive procedures can be fatal to both the fetus and the mother.…”

Section: Introductionmentioning

confidence: 99%

Protein Profiling of Women with Spontaneous Preterm Birth

Zain

et al. 2015

Pharmacology

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Background: Preterm birth (PTB) is the largest cause of neonatal mortality and morbidity in the world. Ethnicity disparity in the occurrence of PTB has been associated with the cytokine function. In this study, we aimed at examining cytokine levels in women with spontaneous preterm and term births. Method: Women with spontaneous preterm birth (SPTB) between 24 and 31 weeks (n = 40) and women with spontaneous term birth between 37 and 41 weeks (n = 40) admitted to the University of Malaya Medical Centre from 2011 to 2013 were involved in this study. Plasma proteins were determined for 35 cytokines using ProcartaPlex™ immunoassay. Protein levels were compared between women with SPTB and women with term birth. Result: Six specific cytokines were significantly high among women with SPTB. This includes TNFA (odds ratio (OR) 3.4, 95% confidence interval (CI) 2.0-6.0, p = 0.001), MCP-3 (OR 2.5, 95% CI 1.29-4.67, p = 0.007), IL16 (OR 2.4, 95% CI 1.34-4.30, p = 0.003), IL17A (OR 2.3, 95% CI 1.28-4.06, p = 0.005), IFNG (OR 3.8, 95% CI 2.0-8.0, p = 0.001), and farctalkine (OR 2.1, 95% CI 1.17-4.22, p = 0.031), respectively. Conclusion: This study identifies high levels of specific cytokines in women with PTB. These inflammatory biomarkers may play an important role in the mechanisms that result in uterine contraction and PTB.

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Chemokines Profiling of Patients with Preterm Birth

Cited by 35 publications

References 22 publications

Human placental syncytiotrophoblasts restrict Toxoplasma gondii vertical transmission at two distinct stages and induce CCL22 in response to infection

Human placental syncytiotrophoblasts restrict Toxoplasma gondii vertical transmission at two distinct stages and induce CCL22 in response to infection

Amniotic Fluid Angiogenic and Inflammatory Factor Profiling in Foetal Down Syndrome

Protein Profiling of Women with Spontaneous Preterm Birth

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