Human Decidual Cells Research Articles

Ceramide stimulates prostaglandin production by human amnion and decidual cells

To determine whether ceramide regulates prostaglandin (PG) production by cultured human amnion cells and decidual cells independently of interleukin-1 beta (IL-1 beta). Cells were grown in monolayer culture and then incubated with varying concentrations of ceramide, IL-1 beta, ceramide in the presence and absence of IL-1, and control media. Production of PGE2 was determined using a specific radioimmunoassay. Ceramide induced a significant concentration-dependent increase in PGE2 production by amnion cells and decidual cells. However, PGE2 production induced by IL-1 beta was significantly more than with ceramide alone, and there was no potentiation of PGE2 production with coincubation of ceramide and IL-1 beta. We suggest that term human amnion cells and decidual cells are responsive to ceramide independent of IL-1 beta and that generation of these substances in response to an infection in the uterus may lead to increased PG production by human gestational tissues, indicating that there are several mechanisms leading to PG production by these cells.

Ceramide Stimulates Prostaglandin Production by Human Amnion and Decidual Cells

Ceramide Stimulates Prostaglandin Production by Human Amnion and Decidual Cells

Lymphocytes of human term decidua decrease cell adhesion to a plastic substrate.

Although human decidual lymphocytes have been widely studied, their function and possible interaction with trophoblast are still unclear. Here we show that whereas human early (EDL) and term (TDL) decidual lymphocytes were unable to kill human trophoblast by necrosis (assessed by the 51Cr-release assay) or apoptosis (DNA fragment assay), TDL but not EDL decreased trophoblast adhesion to a plastic substrate as determined by a [3H]thymidine assay. This effect, however, was not selective for trophoblast, as TDL also decreased the adhesion to plastic of human decidual stromal cells and HeLa cells. Our results suggest that TDL may play a role in placental detachment during parturition by decreasing trophoblast or decidual stromal cell adhesion.

Regulation of Decidual Cell and Chorion Cell Production of Interleukin‐10 by Purified Bacterial Products

To determine whether cultured human decidual cells and chorion cells produce interleukin-10 (IL-10) after incubation with purified bacterial products. Decidual cell cultures and chorion cell cultures were established by standard techniques. With confluence, monolayers of each culture were incubated with purified bacterial products, including various concentrations of lipopolysaccharide (LPS), lipid A, and lipoteichoic acid (LTA) for 16 hr in quadruplicate. Culture supernatants were collected and assayed for immunodetectable IL-10 by enzyme-linked immunoadsorbent assay (ELISA). Both decidual cell cultures and chorion cell cultures produced significant quantities of IL-10 after stimulation with LPS, lipid A, and LTA. Cultures of decidual cells produced more IL-10 than did chorion cell cultures. Our data indicate that both maternal decidual cells and fetally derived chorion cells can produce IL-10 after incubation with bacterial virulence factors. This finding contrasts with our previous findings in which chorion cells did not produce IL-10 after stimulation with IL-1 beta, suggesting that chorion cell production after incubation with bacterial products is independent of IL-1 beta. We speculate that the contribution of anti-inflammatory IL-10 production by human gestational tissues to the inflammatory process in these tissues may be overcome or abrogated by the pro-inflammatory process.

Gene expression and specific binding of platelet-derived growth factor and its effect on DNA synthesis in human decidual cells

To clarify the biological significance of platelet-derived growth factor (PDGF) in human decidual cell function, which is important for the maintenance of pregnancy, we investigated gene expression of the PDGF subunits, PDGF-A and PDGF-B, specific binding of the PDGF isoform, and the effect of PDGF dimers on DNA synthesis in human decidual cells. We detected in decidua from early pregnancy the expected DNA bands of PDGF-A and PDGF-B by reverse transcriptase-polymerase chain reaction (RT-PCR) as well as mRNAs of each PDGF subunit by Northern blot hybridization, demonstrating that both PDGF subunits exist in this tissue. Scatchard plot analysis showed that decidual cells had both PDGF- α and PDGF- β receptors. PDGF-AA, -AB and -BB stimulated [ 3H]-thymidine incorporation in cultured decidual cells in a dose-dependent manner. These results indicate the importance of PDGF in human decidua.

Regulation of decidual cell chemokine production by group B streptococci and purified bacterial cell wall components

Objective: Our purpose was to determine whether cultured human decidual cells produce chemokines in response to different strains of group B streptococci and purified bacterial cell wall components. Study design: Human decidual cells were cultured from term placentas by standard techniques. Different strains of group B streptococci were isolated from neonates with early-onset group B streptococci sepsis. Confluent cell monolayers were incubated with these different strains of group B streptococci and various concentrations of purified bacterial cell wall components (including lipoteichoic acid, sialic acid, lipopolysaccharide, and lipid A) for 16 hours at 37° C. Culture supernatants were collected and assayed for macrophage inflammatory protein-1α and interleukin-8. Statistical analysis was by analysis of variance. Results: We found that cultured human decidual cells produced significant amounts of the two chemokines macrophage inflammatory protein-1α and interleukin-8 in a strain-specific fashion to the various different strains of group B streptococci tested, from 215% to 421% over baseline production ( p < 0.05 by analysis of variance). Also, we found that incubation of decidual cells with various concentrations of lipoteichoic acid, sialic acid, lipopolysaccharide, and lipid A resulted in significant concentration-dependent increases in decidual cell macrophage inflammatory protein-1α and interleukin-8 production ( p < 0.05.) CONCLUSIONS: Decidual cells produced significant amounts of the chemokines macrophage inflammatory protein-1α and interleukin-8 in response to intact group B streptococci in a strain-specific fashion and in response to various concentrations of different bacterial cell wall components. Because chemokines are important mediators signaling migration of different immune effector cells into areas of inflammation, we suggest that decidual cell chemokine production in response to bacteria and bacterial cell wall components may be a key early event in the pathogenesis of infection-associated preterm labor.

Use of “universal bacterial PCR” in a clinical setting

Media from bacterial cultures have been tested for actions on prostaglandin biosynthesis by human amnion and decidual cells. The bacterial species, which are commonly associated with intrauterine infections, were Group B streptococcus, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis, Gardnerella vaginalis, Neisseria gonorrhea, Mycoplasma hominis and Ureaplasma urealyticum. Overall, low doses of bacterial products were stimulatory of amnion prostaglandin production, whereas high doses were inhibitory. A similar pattern of results was obtained for effects on decidual prostaglandin production, although stimulatory actions at low doses were less pronounced. In all experiments interleukin 1 β consistently induced a stimulation of prostaglandin production that greatly exceeded that caused by any bacterial product. It is possible that the inhibitory action of high doses of bacterial products on prostaglandin biosynthesis may contribute to the poor course of labor experienced by women with chorioamnionitis. Furthermore, these data lend credence to the view that the host response to infection (i.e. cytokine secretion) is the major mediator of subsequent preterm labor.

Relationship between the release of prolactin and endothelin-1 in human decidualized endometrial cells.

The study was undertaken to investigate the interaction between the release of endothelin-1 (ET-1) and prolactin (PRL) from human decidualized endometrial cells, and the effects of transforming growth factor (TGF)-beta 1 on the release of ET-1 and PRL from human decidual cells in the early stage of pregnancy. Stromal cells derived from human endometrial tissues were cultured on a type-1 collagen membrane in serum-free medium with or without 100 nmol/l oestradiol and 1 mumol/l medroxyprogesterone acetate (MPA) for 12 days. In addition, decidual cells of early pregnancy were cultured with or without TGF-beta 1 for 48 h. PRL and ET-1 levels in the media were measured by a specific enzyme immunoassay and RIA respectively. In decidualized endometrial cells induced by ovarian steroid hormones in vitro, PRL release increased and ET-1 release decreased in a time-dependent manner. Ovarian steroid hormones significantly attenuated ET-1 release. In the decidual cells of early pregnancy, TGF-beta 1 significantly attenuated the PRL release, whereas this growth factor dose-dependently increased ET-1 release. There was a significant negative correlation between the release of PRL and that of ET-1. These results demonstrate that the regulation of PRL release is quite different from that of ET-1 release in the human decidualized endometrial cells, and suggest that TGF-beta 1 has significant effects on PRL and ET-1 release in the human decidua of early pregnancy.

A three colour flow cytometric technique for measuring TAP1 expression in human extravillous cytotrophoblast and decidual cells

A three colour flow cytometric technique for measuring TAP1 expression in human extravillous cytotrophoblast and decidual cells

P-208. Endothelin receptor expression in human decidual stromal cells

P-208. Endothelin receptor expression in human decidual stromal cells

Evidence for bradykinin B2-receptors on cultured human decidua cells

Bradykinin is known to be present at sites of acute inflammation and to exert its potent inflammatory effects mainly via the bradykinin B2-receptor. Recently, bradykinin dependent processes have been described in cultured human decidual cells, so that bradykinin may expand the list of paracrine factors involved in labour induction. In this paper we present the results of in vitro studies giving evidence that these cells carry the bradykinin B2-receptor. By immunocytochemical methods the receptor protein was localized on decidual cells. Analysis of cellular extracts of cultured decidual cells by RT-PCR showed the presence of the specific mRNA coding for the bradykinin B2-receptor. Binding studies revealed a single, saturable and specific binding site for bradykinin of high affinity (Kd=0.85 nM, Bmax=436 fmol/mg protein). Competitive binding studies showed displacement of [3H]-bradykinin by HOE 140, but not by the ligands for the bradykinin B1-receptor, des-Arg10-kallidin and [Leu8]-des-Arg9-bradykinin. The results are consistent with the presence of the bradykinin B2-receptors.

Human decidual cell biosynthesis of leukemia inhibitory factor: regulation by decidual cytokines and steroid hormones.

The production of leukemia inhibitory factor (LIF) is suggested to be critical for the successful implantation of blastocysts into decidua, because LIF expression is essential for the implantation of mouse blastocytes. We investigated the regulation of LIF production by decidual cytokines and steroid hormones. Stimulation of decidual cells by interleukin-1, tumor necrosis factor alpha, or transforming growth factor beta augmented LIF production in a dose-dependent manner. Moreover, estradiol, a steroid hormone that increases during ovulation and early pregnancy, also enhanced LIF production in a dose-dependent manner. These responses were blocked by protein kinase C (PKC) inhibitor but not by other kinase inhibitors, suggesting an important role of PKC in decidual LIF production mediated by cytokines and estradiol. We also showed that stimulating decidual cells with LIF failed to stimulate DNA synthesis and prolactin production in these cells. In summary, LIF was mainly localized in the decidual glands and stroma, and its production was increased by cytokines and estradiol in a dose-dependent fashion; but stimulation of decidual cells by LIF did not influence their proliferation or their prolactin production.

Phagocytosis by fresh and cultured human decidual stromal cells: opposite effects of interleukin-1α and progesterone

Flow cytometry and transmission electron microscopy have been employed to show that a proportion of fresh and cultured human decidual stromal cells phagocytose latex particles. Phagocytosis of Escherichia coli by cultured decidual stromal cells was, however, very low. Stimulation of cultured decidual stromal cells with interleukin-1α enhanced phagocytosis of both latex particles and E. coli. In contrast, when decidual stromal cells were cultured with progesterone under decidualizing conditions, phagocytic activity was reduced. These results suggest the existence of an immune-endocrine circuit involving decidual stromal cells.

Expression of β_1 Integrins in Human Endometrial Stromal and Decidual Cells

Expression of β_1 Integrins in Human Endometrial Stromal and Decidual Cells

Transforming growth factor-alpha, like epidermal growth factor, stimulates cell proliferation and inhibits prolactin secretion in the human decidual cells in vitro.

In order to clarify the biological action of transforming growth factor alpha (TGF-alpha) in the human decidua, we investigated the effects of TGF-alpha on cell proliferation and prolactin (PRL) secretion in cultured decidual cells in vitro. TGF-alpha had a stimulatory effect on DNA synthesis in decidual cells and an inhibitory effect on PRL secretion from these cells. These results suggest that TGF-alpha, like epidermal growth factor (EGF), may be one of the substances which regulate decidual function.

Regulation of prostaglandin H synthase-2 in chorion and decidual cells

The regulation of chorio-decidual prostaglandin biosynthesis has important implications for our understanding of the mechanisms of human parturition. It has been known for many years that prostaglandin H synthase (PGHS) is a key enzyme in prostaglandin biosynthesis but recently an inducible form (PGHS-2) has been identified that is separate from the constitutive form (PGHS-1). We have evaluated whether substances known to stimulate prostaglandin biosynthesis in chorio-decidua act via PGHS-2. Human chorion and decidual cells were grown to confluence and treated for up to 16 h with interleukin 1β 10 ng/ml), epidermal growth factor (EGF) (10 ng/ml) or phorbol 12-myristate 13-acetate (PMA) (10 −7 M). Microsomal protein was isolated, separated by gel electrophoresis and PGHS-2 amounts determined using an antibody specific for PGHS-2. All three test agents caused an increase in PGHS-2 levels in chorion cells (189%–288%) and decidual cells (153%–541%). Hence, induction of PGHS-2 is one of the mechanisms by which several substances can elevate the rate of prostaglandin biosynthesis.

Effect of interleukin-10 (IL-10) on IL-6 mRNA and cyclooxygenase-II (COX-II) protein expression in human decidual cells

Effect of interleukin-10 (IL-10) on IL-6 mRNA and cyclooxygenase-II (COX-II) protein expression in human decidual cells

A Biological Model for the Regulation of Peri-Implantational Hemostasis and Menstruation

To delineate the physiologic mechanisms whereby the human endometrium maintains hemostasis during endovascular trophoblast invasion but permits menstrual hemorrhage. Experimental results are presented that are relevant to developing a comprehensive biological model for studying peri-implantational hemostasis and menstruation. A marked increase in the expression of tissue factor (TF) and type-1 plasminogen activator inhibitor (PAI-1) and an inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA, respectively), matrix metalloproteinases (MMP), and endothelin-1 (ET-1) expression accompany progestin-induced decidualization of estrogen-primed endometrial stromal cells both in vivo and in vitro. The presence of these important regulators of hemostasis, fibrinolysis, extracellular matrix (ECM) turnover, and vascular tone in decidualized human stromal cells and decidual cells isolated from gestational endometrium suggests a mechanism to explain the absence of hemorrhage during invasion of the endometrial vasculature by trophoblasts. Conversely, progesterone withdrawal reduces TF and PAI-1 expression and increases tPA, uPA, MMP, and ET-1 expression accounting for the hemorrhage, enhanced fibrinolysis, ECM degradation, and ischemic spiral arterial vascular injury characterizing menstruation. Perivascular decidualized endometrial stromal cells are spatially and temporally positioned to promote endometrial hemostasis during implantation but, paradoxically, promote the hemorrhage of menstruation via their hormone-regulated expression of hemostatic, proteolytic, and vasoactive proteins.

β-endorphin inhibits the production of prostaglandin E 2 by human chorio 2-decidual cells in carson

The regulation of chorio-decidual prostaglandin biosynthesis has important implications for our understanding of the mechanisms of human parturition. It has been known for many years that prostaglandin H synthase (PGHS) is a key enzyme in prostaglandin biosynthesis but recently an inducible form (PGHS-2) has been identified that is separate from the constitutive form (PGHS-1). We have evaluated whether substances known to stimulate prostaglandin biosynthesis in chorio-decidua act via PGHS-2. Human chorion and decidual cells were grown to confluence and treated for up to 16 h with interleukin 1β 10 ng/ml), epidermal growth factor (EGF) (10 ng/ml) or phorbol 12-myristate 13-acetate (PMA) (10−7 M). Microsomal protein was isolated, separated by gel electrophoresis and PGHS-2 amounts determined using an antibody specific for PGHS-2. All three test agents caused an increase in PGHS-2 levels in chorion cells (189%–288%) and decidual cells (153%–541%). Hence, induction of PGHS-2 is one of the mechanisms by which several substances can elevate the rate of prostaglandin biosynthesis.

Interferon-y Inhibits the Synthesis and Release of Renin from Human Decidual Cells1

Experiments were performed to examine the effect of interferon-gamma (IFN gamma) on the expression of renin by human uterine decidual cells and decidual macrophages. Exposure of a mixed population of decidual cells consisting of 80% decidualized stromal cells and 20% macrophages to IFN gamma for 4 days caused a dose-dependent inhibition of renin release beginning 2 days after exposure. Renin release on Day 4 was inhibited by a maximum of 83.9%, and the half-maximal effective dose of IFN gamma was 5 ng/ml (290 pM). The inhibition of renin release in response to IFN gamma was accompanied by a comparable inhibition of renin mRNA levels. In addition to inhibiting basal renin expression, IFN gamma potentiated the inhibitory effect of tumor necrosis factor alpha (TNF alpha) on renin expression. IFN gamma also inhibited basal renin release and potentiated the inhibitory effect of TNF alpha by highly purified populations of decidual stromal cells and decidual macrophages prepared by immunomagnetic separation with beads coupled to an anti-human leukocyte antigen (HLA-DR) antibody that binds macrophages but not stromal cells. Reverse transcription-polymerase chain reaction analysis showed that HLA-DR(+) cells express IFN gamma mRNA, and that both HLA-DR(+) and HLA-DR(-) cells express IFN gamma receptors. Since IFN gamma is expressed only by decidual macrophages, the results of this study strongly suggest that IFN gamma inhibits the expression of decidual renin by a paracrine action.