Suppressors of cytokine signaling proteins in human preterm placental tissues

Blumenstein, Marion; Keelan, Jeffrey A.; Bowen-Shauver, Jennifer M.; Mitchell, Murray D.

doi:10.1677/jme.1.01767

Cited by 10 publications

(12 citation statements)

References 27 publications

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“…Hofbauer cells are also regarded as fetal macrophages capable of phagocytosis[109–111] and production of cytokines [e.g., IL-1, IL-8, suppressor of cytokine signaling (SOCS) proteins][112–114], chemokines [e.g. macrophage inhibitory protein (MIP)-1-beta][115] and phagocytosis-related enzymes [acid phosphatase (ACP) and glucose-6-phosphate dehydrogenase (G6PD)][111].…”

Section: Discussionmentioning

confidence: 99%

“…The syncytiotrophoblast is a rich source of immunomodulatory molecules[118–120], and those with immunosuppressive properties [e.g. human chorionic gonadotropin, human placental lactogen, indoleamine 2,3-dioxygenase, CD95L/Fas ligand, pregnancy-specific beta-1 glycoproteins, SOCS proteins, TNF-related apoptosis-inducing ligand (TRAIL)][114,121–126] are proposed to attenuate maternal immune responses and, thus, maintain tolerance to the fetus. The evidence supporting that placental galectin-1 may also have an important role in immune tolerance includes the following: 1) Galectin-1 reduces host alloreactivity and ameliorates graft versus host disease in mice[81]; 2) it is capable of triggering the apoptosis of immature thymocytes[105] and activated T cells[75], biasing the immune responses to the Th2 type[63,127,128], and suppressing experimental T cell-mediated autoimmune diseases (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Severe preeclampsia is characterized by increased placental expression of galectin-1

Than

Erez

Wildman

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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Objective Galectin-1 is a major anti-inflammatory protein expressed by the placenta and immune cells that can bias the character of inflammatory responses toward the Th2 type. Galectin-1 is expressed in immune privileged sites, it can facilitate immune tolerance and tumor immune escape, and it has been successfully used for the suppression of experimental autoimmune diseases as well as graft versus host disease in murine models. We propose that an abnormal immune response in some pregnancy complications may be associated with changes in placental expression of galectin-1. To test this hypothesis, we studied placental galectin-1 mRNA and protein expression and localization in women with preeclampsia (PE) and in those who delivered a small-for-gestational age (SGA) neonate. Study design This cross-sectional study included pregnant women matched for gestational age at delivery in the following groups: 1) severe PE (n=10); 2) severe PE complicated with SGA (n=10); 3) SGA without PE (n=10); and 4) controls (n=10). Galectin-1 mRNA and protein were localized in placentas by in situ hybridization and immunofluorescence microscopy. Galectin-1 mRNA expression was determined by quantitative real-time RT-PCR, and galectin-1 protein content by Western blot. Non-parametric statistics were used for analysis. Results 1) In normal term placentas, galectin-1 mRNA or immunofluorescence signals were detected in the trophoblasts, villous stromal cells, Hofbauer cells, endothelial cells of the villous blood vessels,,and the villous stroma. 2) Placental galectin-1 mRNA expression was significantly higher in severe PE (with or without SGA) than in controls (1.47 fold, p=0.004; 1.44 fold, p=0.003; respectively] and in SGA (1.68 fold, p=0.001; 1.64 fold, p=0.001; respectively]. 3) Trophoblasts in placentas of patients with severe PE had the most intense galectin-1 immunostaining. Conclusion 1) We report for the first time the placental expression and localization of galectin-1 mRNA and demonstrate that the protein is abundantly present in third trimester human placentas. 2) Placental galectin-1 expression is higher in severe PE than in normal pregnancy regardless of the presence of SGA. 3) However, it is not altered in SGA without PE. We propose that the increased placental expression of galectin-1 in patients with severe PE may represent a fetal response to an exaggerated systemic maternal inflammation; thus, galectin-1 may be implicated in maternal-fetal immune tolerance in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Severe preeclampsia is characterized by increased placental expression of galectin-1

Than

Erez

Wildman

et al. 2008

The Journal of Maternal-Fetal & Neonatal Medicine

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“…Genetic crosses between mice heterozygous for deletion of SOCS3 and LIFRα (null mutants for each is lethal) revealed that the phenotype is due to dysregulation of signaling downstream of the LIFR and that the ligand responsible for this, LIF, is produced by embryonic tissues and acts in a paracrine fashion 28 , 95 . In human placenta SOCS1, SOCS2, and SOCS3 mRNA and protein are detectable in pre-term and term villous placenta and immunohistochemical analysis localized all three SOCS proteins to all decidual cells 97 , 98 . Interestingly, decreased SOCS3 expression has also been observed in the villous tissue of placentae obtained from women with preeclampsia 99 .…”

Section: Syncytialization Of Trophoblasts: Relevance Of Lif-stat Signmentioning

confidence: 99%

LIF-STAT signaling and trophoblast biology

2013

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Leukemia inhibitory factor (LIF) is a pleiotropic growth factor that regulates several biological functions. This review focuses on the LIF-dependent STAT activation and its impact on modulation of trophoblast functions during embryo implantation. LIF is mainly produced by the maternal endometrium at the time of implantation while its receptors are present both on the endometrium and trophoblasts. It might influence blastocyst attachment through STAT3 activation and expression of integrins. After attachment of the blastocyst, trophoblasts undergo proliferation and differentiation into invasive EVTs and non-invasive STBs. Under in vitro conditions, LIF regulates all these processes through activation of STAT- and MAPK-dependent signaling pathways. The observations that LIF and STAT3 knockout mice are infertile further strengthen the notion about the critical involvement of LIF-mediated signaling during embryo implantation. Hence, a better understanding of LIF-STAT signaling would help in improving fertility as use of LIF in in vitro blastocyst culture improves the implanting ability of blastocyst after IVF.

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“…Proinflammatory cytokines and immune related chemokines stimulate prostaglandin production and uterine contraction through mechanisms that involve cycloxygenase-2 [34,40,41]. They act on cervical smooth muscles enhancing cervical ripening, activate matrix metalloproteinasess expression; and, increase protease production leading to extracellular matrix degradation, related cervical changes and premature rupture of membrane [34,40,41].…”

Section: Discussionmentioning

confidence: 99%

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

Enquobahrie

Williams

Qiu

et al. 2009

BMC Pregnancy Childbirth

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BackgroundPreterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.MethodsAs part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip® Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.ResultsA total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.ConclusionsPTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.

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Suppressors of cytokine signaling proteins in human preterm placental tissues

Cited by 10 publications

References 27 publications

Severe preeclampsia is characterized by increased placental expression of galectin-1

Severe preeclampsia is characterized by increased placental expression of galectin-1

LIF-STAT signaling and trophoblast biology

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

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