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ABSTRACT: PROBLEM: Macrophage function has many implications in a variety of diseases. Understanding their biology becomes imperative when trying to elucidate immune cell interactions with their environment, and in vitro cell lines allow researchers to manipulate these interactions. A common cell line used is THP-1, a promyeloid cell line suggestive to outside factors, and therefore sensitive to culture conditions. In this study, we describe how culture conditions can alter THP-1 morphology and in turn affect their response to differentiation stimuli. METHOD OF STUDY: THP-1 cells were cultured in two conditions and treated with phorbol 12-myristate 13-acetate (PMA) or MCSF. CD14 surface expression was determined by flow cytometry and cytokine/chemokine production determined by multiplex analysis. RESULTS: Culture conditions of THP-1 affect their response to PMA. Highly confluent THP-1 cells differentiate into a heterogeneous population responsive to PMA as seen by an increase in CD14 expression. However, these cells, cultured in low confluence, remain as a homogenous population and do not gain CD14. Additionally, there are major differences in the constitutive cytokine profile. CONCLUSION: We demonstrate that the culture conditions of THP-1 cells can alter their response PMA. This suggests that culture techniques may account for the discrepancy in the literature of both basal THP-1 phenotype and their response to PMA.
American Journal Of Reproductive Immunology 04/2013; · 2.17 Impact Factor
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ABSTRACT: PROBLEM: Pre-eclampsia (PE), a pregnancy complication of unknown etiology, is a major cause of maternal and fetal mortality and morbidity. Previous studies have described placental genes that are up-regulated in expression in PE, but few studies have addressed placental gene suppression in this syndrome. METHOD OF STUDY: Gene profiling and quantitative reverse transcription PCR (qRTPCR) analyses were used to identify genes down-regulated in placentas from women with severe preterm PE compared with gestational age-matched normotensive controls with spontaneous preterm birth (sPTB). Western blotting and immunohistochemistry were used to evaluate levels and patterns of cell type-specific protein expression in PE and sPTB group placentas. RESULTS: Levels of macrophage marker [folate receptor (FR)-β, CD163, and CD68] mRNA and FR-β protein were significantly down-regulated in PE group placentas compared with the sPTB group. Numbers of Hofbauer cells (HBCs, fetal macrophages) and FR-β protein in these cells were reduced in PE group placentas. CONCLUSION: Severe PE is associated with decreased placental expression of FR-β and a reduction in the number of HBCs. Reduced placental macrophage function is likely to play a key role in the pathophysiology of PE.
American Journal Of Reproductive Immunology 03/2013; · 2.17 Impact Factor
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ABSTRACT: PROBLEM: There is a strong correlation between intrauterine bacterial infection and preterm labor. While inflammation is a common mechanism, certain pathogens may trigger placental apoptosis. TLR2 activation by gram-positive bacterial peptidoglycan (PDG) induces first-trimester trophoblast apoptosis and decreased IL-6 secretion. This is dependent upon the presence of TLR1 and the absence of TLR6 and both TLR2 coreceptors. As TLR10 is also a TLR2 coreceptor, the objective of this study was to determine its expression and function in the trophoblast. METHOD OF STUDY: First-and third-trimester human placental tissue and isolated trophoblast were evaluated for TLR10 expression. A first-trimester human trophoblast cell line stably transfected with a TLR10 dominant negative (TLR10-DN) or vector control was treated with or without PDG and analyzed for apoptosis and IL-6. RESULTS: TLR10 was expressed by trophoblasts during the first and third trimesters of pregnancy. PDG-induced trophoblast caspase-3 activity was inhibited by the presence of the TLR10-DN. The presence of the TLR10-DN had no effect on PDG reduction in trophoblast IL-6 secretion. CONCLUSION: This study demonstrates that trophoblast TLR10 plays a role in promoting apoptosis triggered by gram-positive bacterial components and suggests that TLR10 may regulate the balance between trophoblast survival and cell death.
American Journal Of Reproductive Immunology 12/2012; · 2.17 Impact Factor
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ABSTRACT: Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate receptor-β (FR-β), markers of antiinflammatory M2 macrophages, were specifically expressed by primary cultures of HBCs immunopurified from human term placentas. GC receptor mRNA and protein levels were higher in HBCs compared with placental fibroblasts. Treatment of HBCs with cortisol or dexamethasone (DEX) markedly and specifically enhanced CD163 protein and mRNA levels, whereas expression of FR-β and CD68 were largely unresponsive to GC treatment. DEX treatment also increased hemoglobin uptake by HBCs, evidence of enhanced HBC function. The level of CD163 mRNA, but not FR-β or CD68 mRNA, was stimulated in placental explant cultures by DEX treatment, and increased CD163/FR-β and CD163/CD68 mRNA ratios sensitively reflected the response to GC. Maternal GC administration was associated with increased CD163/FR-β and CD163/CD68 mRNA ratios in placentas from women with spontaneous preterm birth. In conclusion, in vitro studies indicated that GC treatment specifically up-regulated CD163 expression in HBCs and enhanced HBC function. In addition, the observed alterations in patterns of expression of macrophage marker genes associated with maternal GC administration suggest that HBCs are in vivo targets of GC action.
Endocrinology 11/2012; · 4.46 Impact Factor
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ABSTRACT: Uterine innate immunity remains poorly characterized, and while endometrial endothelial cells are known to express Toll-like receptors (TLRs), little is known about their function in these cells. The present study evaluated the effect of Gram-negative bacterial lipopolysaccharide (LPS) on human endometrial endothelial cell (HEECs) cytokine secretion and tissue factor expression, and the role of TLR-4 in these responses.
Human endometrial endothelial cells were treated with or without LPS ± LPS-RS, a TLR-4 antagonist, via the binding of MD-2. After 24 hr, cell-free supernatants were evaluated for cytokines by multiplex analysis and cell lysates were analyzed for tissue factor expression by Western blot.
Treatment of HEECs with LPS significantly upregulated the secretion of IL-6, IL-8, and G-CSF, and this was prevented by LPS-RS. LPS also induced tissue factor expression by the HEECs; however, this was unaffected by LPS-RS.
These findings suggest that TLR-4 is functional in HEECs and its activation by bacterial LPS induces a specific cytokine/chemokine response. However, bacterial LPS also induced tissue factor expression in what seemed to be a TLR-4-independent fashion, suggesting that this bacterial component can act on the HEECs through TLR-4-dependent and TLR-4-independent pathways. These findings indicate that endometrial endothelial cells may play an active role in uterine innate immunity.
American Journal Of Reproductive Immunology 06/2012; 68(3):233-7. · 2.17 Impact Factor
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ABSTRACT: Toll-like receptor-4 (TLR-4) protects against Gram-negative bacteria expressed lipopolysaccharide and 'danger signals' from injured or dying cells. Although decidual cells (DCs) and interstitial trophoblasts (ITs) are in close contact, TLR-4 has been studied extensively only in ITs.
Formalin-fixed, paraffin-embedded serial sections of endometrium in follicular and luteal phases and deciduas from first and second trimester elective terminations and third trimester normal deliveries were immunostained for TLR-4, trophoblast-specific cytokeratin, and DC-specific vimentin. HSCORE assessed TLR-4 immunostaining in DCs versus ITs.
TLR-4 HSCORES were significantly higher in: (i) first trimester DCs than luteal phase pre-decidual stromal cells; (ii) first and third versus second trimester DCs, but similar between third trimester deciduas parietalis and basalis; (iii) first versus second trimester ITs; (iv) DCs versus ITs across gestation.
Higher TLR-4 in DCs than ITs suggests DCs as primary targets for Gram-negative bacteria and/or inflammation-related danger signals.
American Journal Of Reproductive Immunology 05/2012; 68(2):146-53. · 2.17 Impact Factor
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ABSTRACT: There is a strong association between infection and prematurity; however, the underlying mechanisms remain largely unknown. Nod1 and Nod2 are intracellular pattern recognition receptors that are activated by bacterial peptides and mediate innate immunity. We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation. This study sought to determine the expression and function of Nod1 and Nod2 in third-trimester trophoblasts, and to characterize the in vivo effects of Nod1 activation on pregnancy outcome. Human term placental tissues and isolated term trophoblast expressed Nod1, but not Nod2. Activation of Nod1 by its agonist, bacterial γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP), in term trophoblast cultures induced a proinflammatory cytokine profile, characterized by elevated levels of secreted IL-6, GRO-α, and MCP-1, when compared with the control. However, these cytokines were not upregulated in response to Nod2 stimulation with bacterial MDP. Administration of high-dose bacterial iE-DAP to pregnant C57BL/6J mice on embryonic day 14.5 triggered preterm delivery within 24 h. iE-DAP at a lower dose that did not induce prematurity, reduced fetal weight, altered the cytokine profile at the maternal-fetal interface, and induced fetal inflammation. Thus, functional Nod1 is expressed by trophoblast cells across gestation and may have a role in mediating infection-associated inflammation and prematurity. This study demonstrates that pattern recognition receptors, other than the TLRs, may be implicated or involved in infection-associated preterm labor.
The Journal of Immunology 06/2011; 187(2):980-6. · 5.79 Impact Factor
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ABSTRACT: PROBLEM Placental villus macrophages (i.e., Hofbauer cells, HBCs) were identified more than 100 years ago. Alterations in their numbers and characteristics are associated with several complications of pregnancy. Although HBCs have previously been isolated and cultured, there is no consensus methodology to obtain these cells with high yield and purity for in vitro studies. METHOD OF STUDY Hofbauer cells were isolated from human term placentas using protocols in which cytotrophoblasts (CTs) and fibroblasts (FIBs), other major villous cell types, were isolated in parallel. Enzymatic digestion, Percoll gradients, and immunoselection were used to isolate the three cell types. Purity was assessed by morphology, flow cytometry, and phagocytosis assays. RESULTS Hofbauer cells were isolated with 98-99% purity and a yield of 130-200 × 10(6) cells/80-100 g of tissue. HBCs exhibited a pleiomorphic and vacuolated appearance for at least 5 days in culture medium with and without serum. High levels of phagocytosis in HBCs, but not in CTs or FIBs, confirmed macrophage function in HBCs. Phagocytotic activity was maintained across several days in culture. CONCLUSION Hofbauer cells were isolated from term placenta with high yield and purity using protocols in which CTs and FIBs were also obtained. This methodology will foster future studies that examine the role of HBCs in regulating villus function.
American Journal Of Reproductive Immunology 05/2011; 66(4):336-48. · 2.17 Impact Factor
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ABSTRACT: Hofbauer cells (HBCs) are placental macrophages that are present in the villus across gestation. Despite their identification more than 100 years ago, their specific role in placental function remains largely unelucidated. We initially review aspects of their history and biology as well as evidence for putative sites of origin. To gain insight into their potential function, we then describe complications of pregnancy including villitis of unknown etiology (VUE) and histological chorioamnionitis (HCA), in which alterations in numbers, gene expression, or other characteristics of HBCs have been documented to occur. We further review methods for isolation of HBCs and in vitro studies that explore their role in relation to other major cell types in the placenta and examine their actions in cytokine-mediated inflammation. We conclude that HBCs play a key role in placental pathophysiology, and future advances in their isolation and culture would enable mechanistic insight into their villus function.
Annals of the New York Academy of Sciences 03/2011; 1221:103-8. · 3.15 Impact Factor
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ABSTRACT: The concept that pregnancy is associated with immune suppression has created a myth of pregnancy as a state of immunological weakness and, therefore, of increased susceptibility to infectious diseases. A challenging question is whether the maternal immune system is a friend or a foe of pregnancy. In this review, we discuss data associated to the role of the immune system during pregnancy. We propose a new paradigm in terms of the fetal-maternal immune interaction as well as the immunological response of the mother to microorganism. Our challenge is to better understand the immunology of pregnancy in order to deliver the appropriate treatment to patients with pregnancy complications as well as to determine public policies for the protection of pregnant women during pandemics.
Annals of the New York Academy of Sciences 03/2011; 1221:80-7. · 3.15 Impact Factor
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Serkalem Tadesse,
Guoyang Luo,
Joong Shin Park,
Byoung Jae Kim,
Victoria V Snegovskikh,
Ting Zheng,
Eric J Hodgson,
Felice Arcuri,
Paolo Toti,
Chirag R Parikh, Seth Guller,
Errol R Norwitz
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ABSTRACT: Neutrophil gelatinase-associated lipocalin (NGAL) is a ubiquitous lipocalin that serves as a critical component of innate immunity and a transport shuttle for numerous substances (retinoids, arachidonic acid, prostaglandins, fatty acids, steroids, iron, and MMPs). Despite the well-documented association between intra-amniotic infection/inflammation (IAI) and preterm birth, NGAL expression in the uterus has not previously been examined. This study investigates NGAL expression at the maternal-fetal interface in vivo and in vitro.
Neutrophil gelatinase-associated lipocalin expression in term placenta with/without IAI was examined by immunohistochemistry. Trophoblast and decidual stromal cells were retrieved from elective cesarean, purified, and depleted of leukocytes. On days 1 (cytotrophoblast cells) and 4 (syncytiotrophoblast), cells were stimulated with/without interleukin 1β (IL-1β; 1 ng/mL), tumor necrosis factor α (TNF-α; 1 ng/mL), or lipopolysaccharide (LPS; 1 μg/mL). Neutrophil gelatinase-associated lipocalin messenger RNA (mRNA) and protein expression were measured by immunocytochemistry/Western blot and RT-qPCR, respectively.
Under basal conditions, NGAL is expressed in trophoblast, but not decidua. Trophoblast NGAL is significantly upregulated in tissues with evidence of IAI vs controls. NGAL expression was increased after stimulation with all 3 pro-inflammatory mediators in day 1 (cytotrophoblast) but not day 4 cells (syncytiotrophoblast). IL-1β and TNF-α (not LPS) upregulated NGAL gene expression in cytotrophoblast (not syncytiotrophoblast) cells.
Intra-amniotic infection/inflammation is associated with increased expression of NGAL in trophoblast tissues in vivo. IL-1β, TNF-α, and LPS stimulated NGAL in cytotrophoblast cells (not syncytiotrophoblast and decidua) in vitro. These data suggest that, in keeping with its role as a mediator of innate immunity, NGAL may have a central role to play in IAI-induced preterm birth.
Reproductive sciences (Thousand Oaks, Calif.) 03/2011; 18(8):713-22. · 2.31 Impact Factor
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ABSTRACT: Preeclampsia is associated with hyperuricemia, which correlates with the disease severity. Levels of circulating uric acid increase before the clinical manifestations, suggesting that they may be causally related. Uric acid, or monosodium urate (MSU), activates the Nod-like receptor, Nalp3, leading to inflammasome activation and IL-1β processing. Because preeclampsia is associated with placental immune⁄ inflammatory dysregulation, we sought to determine in the trophoblast, the presence of the Nalp3 inflammasome, and the effect of MSU on its activation.
Isolated first- and third-trimester trophoblasts were assessed for expression of the inflammasome components, Nalp1, Nalp3, and ASC. First-trimester trophoblast cells were incubated with or without MSU, and after which, IL-1β secretion and processing and caspase-1 activation were determined.
Trophoblast cells expressed Nalp1, Nalp3, and ASC under basal conditions. Following incubation with MSU, first-trimester trophoblast IL-1β secretion was upregulated. This correlated with increased expression levels of active IL-1β and active caspase-1. ASC knockdown reduced MSU-induced IL-1β secretion.
These findings demonstrate that uric acid activates the inflammasome in the trophoblast, leading to IL-1β production. This may provide a novel mechanism for the induction of inflammation at the maternal–fetal interface leading to placental dysfunction and adverse pregnancy outcome, including preeclampsia.
American Journal Of Reproductive Immunology 01/2011; 65(6):542-8. · 2.17 Impact Factor
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ABSTRACT: To investigate the expression and function of GnRH and GnRH receptor (GnRHR) subtypes at the maternal-fetal interface.
In vitro experiments using freshly isolated human trophoblast cells, decidual stromal cells (DSCs), and immortalized cell lines.
University teaching hospital.
Placenta-fetal membranes from term deliveries.
Human trophoblast and DSCs were isolated, purified, and cultured.
Expression of GnRH-I, GnRH-II, and GnRHR-I mRNA and protein in human trophoblast cell lines and tissues were evaluated by reverse-transcription polymerase chain reaction and Western blot. The effect of GnRH-I and -II on the production of select cytokines (hCG, interleukin [IL] 8, IL-6, matrix metalloproteinase 3, monocyte chemoattractant protein 1, vascular endothelial growth factor, soluble Fms-like tyrosine kinase 1, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1) were measured by ELISA and normalized for protein content.
GnRH-I, GnRH-II, and GnRHR-I mRNA and protein were identified in trophoblasts and decidua. GnRH-I and -II stimulated hCG production by trophoblast and trophoblast-derived cell lines in a dose-dependent fashion (e.g., 2.8-fold, from 2.5 ± 0.5 to 7.0 ± 0.4 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-I and 2.4-fold, from 2.5 ± 0.5 to 6.1 ± 0.6 ng/mg protein per 24 h, for 1,000 nmol/L GnRH-II) without affecting the production of other cytokines.
Trophoblasts and decidua express GnRH-I, GnRH-II, and GnRHR-I mRNA and protein. GnRH-I and -II selectively stimulate hCG production by trophoblast cells without altering the production of select cytokines by trophoblasts or decidua. The role of GnRH-GnRHR signaling at the maternal-fetal interface therefore appears to be limited to the regulation of trophoblast hCG production.
Fertility and sterility 12/2010; 94(7):2680-7. · 3.97 Impact Factor
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Paolo Toti,
Felice Arcuri,
Zhonghua Tang,
Frederick Schatz,
Eduardo Zambrano,
Gil Mor,
Tracy Niven-Fairchild,
Vikki M Abrahams,
Graciela Krikun,
Charles J Lockwood, Seth Guller
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ABSTRACT: Histopathological chorioamnionitis (HCA) is caused by microbial-driven infiltration of leukocytes to the maternal-fetal interface resulting in adverse neonatal outcomes in a subset of pregnancies. The role of placental villus macrophages (i.e. Hofbauer cells, HBCs) in the pathophysiology of HCA is unelucidated.
The number of HBCs in human term placental villi in HCA and control groups was compared using immunohistochemistry. Levels of monocyte chemotactic protein (MCP-1) expression were measured in primary cultures of syncytioytrophoblasts (SCTs) and fibroblasts (FIBs) treated with bacterial compounds [lipopolysaccharide (LPS) and peptidoglycan] and pro-inflammatory cytokines (TNF-α and IL-1β) using ELISA and quantitative real-time PCR.
Immunohistochemistry revealed a focal increase in HBCs in HCA. Treatment of FIBs with LPS, IL-1β, and TNF-α significantly increased MCP-1 mRNA and protein expression. Conversely, MCP-1 mRNA and protein levels were virtually undetectable in treated and untreated SCTs.
These results demonstrate cell-type-specific regulation of MCP-1 expression in human placenta. A model is presented in which bacterial products and inflammatory cytokines initiate a fibroblast-driven cytokine cascade resulting in recruitment of fetal monocytes to placenta which focally increases levels of HBCs in pregnancies complicated by HCA.
American Journal Of Reproductive Immunology 11/2010; 65(5):470-9. · 2.17 Impact Factor
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ABSTRACT: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast.
The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR.
Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFkappaB inhibitor and a TLR4-dominant negative (DN).
This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFkappaB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.
American Journal Of Reproductive Immunology 05/2009; 61(4):294-302. · 2.17 Impact Factor
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ABSTRACT: Problem: The cytoplasmic pattern recognition receptors, Nod1 and Nod2, are thought to be important for detecting intracellular bacteria. We have previously reported that first trimester trophoblast cells express Nod1 and Nod2, and that trophoblast Nod2 activation triggers an inflammatory response. The objectives of this study were to characterize the effects of Nod1 stimulation, and to determine the regulation of Nod1 and Nod2, in the trophoblast.Method of Study: The effect of Nod1 activation on trophoblast cells was determined by analyzing the cytokine response following treatment with γ-D-glutamyl-meso-diaminopimelic acid (iE-DAP). The regulation of Nod1 and Nod2 expression by trophoblast cells was evaluated by RT-PCR.Results: Treatment of trophoblast cells with iE-DAP significantly increased their production of cytokines and chemokines. In addition, Nod1 and Nod2 mRNA expression was upregulated following treatment of trophoblast cells with lipopolysaccharide (LPS), and this was significantly reduced by the presence of a NFκB inhibitor and a TLR4-dominant negative (DN).Conclusion: This study demonstrates that LPS, through TLR4, increases trophoblast expression of Nod1 and Nod2 via the NFκB pathway; and that Nod1 is functional in the trophoblast. These findings suggest that extracellular recognition of bacterial LPS by TLR4 may prime the trophoblast in preparation for its cytoplasmic recognition of, and response to, bacterial peptides through the Nod proteins.
American Journal Of Reproductive Immunology 03/2009; 61(4):294 - 302. · 2.17 Impact Factor
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ABSTRACT: There is consensus that ischemia/reperfusion injury associated with preeclampsia (PE) promotes both placental damage and the release of factors leading to maternal endothelium dysfunction, a hallmark of this potentially life-threatening syndrome. These factors include plasminogen activator inhibitor-1 (PAI-1) and soluble fms-like tyrosine kinase-1 (sFlt-1). The goal of this study was to further characterize placental factors involved in the pathophysiology of PE. Thus, DNA microarray gene profiling was utilized to identify mRNA differentially regulated in placentas from women with severe PE compared to both preterm (PC) and term control (TC) groups. Microarray studies detected an upregulation of mRNA for ceruloplasmin, a copper-containing iron transport protein with antioxidant ferroxidase properties, in PE compared to PC and TC placentas, respectively. Quantitative real-time PCR confirmed these results by demonstrating significant increases in ceruloplasmin mRNA in PE vs PC and TC placentas. Supporting previous reports, the expression of sFlt-1 and PAI-1 were also upregulated in PE placentas. Immunohistochemistry localized ceruloplasmin to the intervillous space in PE and PC placentas, whereas stronger syncytial staining was noted in PE. Western blotting confirmed a significant increase in ceruloplasmin levels in placental tissue in PE compared to PC groups. PCR identified the presence of mRNA for ceruloplasmin in primary cultures of syncytiotrophoblasts, but not villous-derived fibroblasts, suggesting that syncytium is the site of ceruloplasmin synthesis in placenta. Hypoxic treatment (1% O(2)) of syncytiotrophoblasts enhanced levels of ceruloplasmin mRNA approximately 25-fold, a significantly greater upregulation than that noted for PAI-1 and sFlt-1, suggesting that enhanced ceruloplasmin expression is a sensitive marker of syncytial hypoxia. We suggest that syncytial ceruloplasmin and its associated ferroxidase activity, induced by the hypoxia accompanying severe PE, is important in an endogenous cellular program to mitigate the damaging effects of subsequent reperfusion injury at this site.
Laboratory Investigation 09/2008; 88(10):1057-67. · 3.64 Impact Factor
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Annals of the New York Academy of Sciences 05/2008; 1127:xi. · 3.15 Impact Factor
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ABSTRACT: Preeclampsia is associated with an increased release of factors from the placental syncytium into maternal blood, including the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin, the antifibrinolytic factor plasminogen activator inhibitor-1, prostanoids, lipoperoxides, cytokines, and microparticles. These factors are suggested to promote maternal endothelium dysfunction and are associated with placental damage in pregnancies also complicated with intrauterine growth restriction (IUGR). In this report, we briefly describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and IUGR. Given the critical role of the syncytium in these complications of pregnancy, we also present a novel methodology in which laser capture microdissection followed by Western blotting is used to assess levels of syncytial Fas ligand, a key protein in the apoptotic cascade.
Annals of the New York Academy of Sciences 05/2008; 1127:129-33. · 3.15 Impact Factor
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ABSTRACT: Preeclampsia is associated with an increased release of factors from the placental syncytium into maternal blood, including the antiangiogenic factors soluble fms-like tyrosine kinase-1 and soluable endoglin, the antifibrinolytic factor plasminogen activator inhibitor-1, prostanoids, lipoperoxides, cytokines, and microparticles. These factors are suggested to promote maternal endothelium dysfunction and are associated with placental damage in pregnancies also complicated with intrauterine growth restriction (IUGR). In this report, we briefly describe the interaction of syncytial factors with hypoxia, reactive oxygen species, and apoptosis in the pathophysiology of preeclampsia and IUGR. Given the critical role of the syncytium in these complications of pregnancy, we also present a novel methodology in which laser capture microdissection followed by Western blotting is used to assess levels of syncytial Fas ligand, a key protein in the apoptotic cascade.
Annals of the New York Academy of Sciences 04/2008; 1127(1):129 - 133. · 3.15 Impact Factor
