Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Among risk factors for vertical transmission of HIV there are listed concomitant viral and bacterial infections. Therefore the influence on the viruses replication in human placenta and amniotic membrane cultures of double viral infection with two unrelated viruses - encephalomyocarditis (EMCV) and vesicular stomatitis virus (VSV) - was studied and compared with the replication of the viruses in single virus infection (EMCV or VSV) in the same organ cultures. Additionally effect of bacterial factors - lipopolysaccharide (LPS) Escherichia coli and sonicated Treponema pallidum antigens (Tpa) - on VSV replication in the same culture system was studied and compared with VSV replication in untreated explants. Two effects were observed in double-virus infected cultures and also in bacterial factors treated cultures: inhibition and stimulation of virus replication. The kind of effect in the both cases was dependent on the presence or absence of innate antiviral immunity. In virus-sensitive organs double infected or treated with LPS or Tpa, inhibition of virus titer (2-5 log TCID(50)/ml) was observed. In the organs expressing the innate immunity, stimulation (1-4 log TCID(50)/ml) of virus replication was noticed. Contribution of endogenous TNFalpha in both reactions (stimulation and inhibition) was confirmed using antibodies against the TNF.
Placenta 2001 Apr
PMID:Study on risk factors for transplacental viral infections; effect of bacterial factors and double viral infections on virus replication in placenta and amniotic membranes. 1128 73

Placental hypoxia, ischaemia, reperfusion and resultant oxidative stress, with the release of various factors into the maternal vasculature acting as mediators of endothelial cell dysfunction, play an important role in the development of pre-eclampsia. Human term placental tissue explants were exposed to different stressors, e.g. hypoxia, oxidative stress and lipopolysaccarides, and the effect on the release of prostanoids and cytokines was determined. The hypoxic environment consisted of 2 per cent O2, 5 per cent CO2and 93 per cent N2. Oxidative stress was induced by addition of xanthine together with xanthine oxidase to the incubation medium. As a third experimental variable, lipopolysaccharide was added to the medium. Prostaglandins (8-iso-PGF(2alpha), or 6-keto-PGF(1alpha)and TXB(2)as stable metabolites of prostacyclin and thromboxane, respectively) and cytokines (TNF-alpha, IL-1alpha, IL-1beta, IL-6) were measured using commercial ELISA assays. Under control conditions, the production of prostaglandins in ng/24 h (mean +/- s.d.) was 6 +/- 3 for 8-iso-PGF(2alpha), 19 +/- 9 for 6-keto-PGF(1alpha)and 5 +/- 2 for TXB2. The production of cytokines was 13 +/- 6 pg for TNF-alpha, 7 +/- 2 pg for IL-1alpha, 5 +/- 3 pg for IL-1beta and 18 +/- 9 ng for IL-6. Under hypoxia the production of prostaglandins remained unchanged and of the cytokines only IL-1beta showed a 15-fold increase. Oxidative stress resulted in an increase in the release of prostaglandins and of cytokines of 4- to 15- and 3- to 130-fold, respectively. Lipopolysaccharides and oxidative stress had a similar effect on the production of prostaglandins, whereas the stimulatory effect of lipopolysaccharides on cytokines was significantly higher than that of oxidative stress.
Placenta 2001 Apr
PMID:Effect of hypoxia, oxidative stress and lipopolysaccharides on the release of prostaglandins and cytokines from human term placental explants. 1131 28

We and others have previously observed an imbalance in cytotrophoblast secretion of the vasoactive prostanoids prostacyclin and thromboxane A(2) in pre-eclampsia. To examine the effects of potential modulators of this imbalance, cytotrophoblasts isolated from normal and pre-eclamptic pregnancies were incubated in the presence of lipopolysaccharide, the calcium ionophore A23187, tumour necrosis factor alpha, or interleukin 1beta, with or without the cyclo-oxygenase inhibitor, indomethacin. Further incubations included the drugs tranylcypromine, a prostacyclin synthetase inhibitor (0.1, 10 microM ), or the thromboxane synthetase inhibitor, pirmagrel (0.001, 1 microM ). Results showed that cytotrophoblasts from pre-eclamptic pregnancies had increased thromboxane production and significant stimulation of prostacyclin production by lipopolysaccharide and calcium ionophore. Lipopolysaccharide stimulated thromboxane production in normal cytotrophoblasts, while indomethacin almost completely inhibited production of both prostanoids. Tranylcypromine mildly inhibited prostacyclin production in normal cytotrophoblasts only, whereas pirmagrel strongly inhibited thromboxane production in a dose-related manner, with reciprocal increase in prostacyclin production occurring in cytotrophoblasts from pre-eclamptic pregnancies. This study confirmed that cytotrophoblasts from pre-eclamptic women had increased thromboxane production and showed that pirmagrel, at the relatively low dose of 0.001 microM, was able to normalize the imbalance of thromboxane and prostacylin production and may therefore warrant further investigation as a treatment for pre-eclampsia.
Placenta
PMID:Modulation of prostacyclin and thromboxane secretion by cytotrophoblasts from normal and pre-eclamptic human pregnancies. 1236 79

The aim of this study was to 1) profile the basal release of TNF-alpha, IL-6, IL-8, and 8-isoprostane (a marker of oxidative stress); and 2) investigate the effect of stimulation on the release of cytokines from sc adipose tissue and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus (GDM). Placenta, sc adipose tissue, and skeletal muscle were incubated in the absence (control) or presence of lipopolysaccharide (LPS; 10 microg/ml), TNF-alpha (10 ng/ml), IL-6 (10 ng/ml), or IL-8 (10 ng/ml). After an 18-h incubation, the medium was collected, and the release of TNF-alpha, IL-6, IL-8, and 8-isoprostane was quantified by ELISA. In all three tissues, 8-isoprostane release was greater in women with GDM, and stimulation with LPS increased 8-isoprostane release from adipose and skeletal muscle, but not placenta, obtained from women with GDM. However, in tissues obtained from normal pregnant women, LPS stimulation increased 8-isoprostane release in placenta and had no effect in adipose tissue and skeletal muscle. Their was no difference in the release of TNF-alpha, IL-6, and IL-8 from placenta, adipose tissue, and skeletal muscle obtained from normal pregnant women and women with GDM. Stimulation of placenta, adipose tissue, and skeletal muscle with LPS and TNF-alpha resulted in greater release of IL-6 and IL-8, whereas only LPS increased TNF-alpha release from all three tissues. The data presented in this study demonstrate that there is a differential release of 8-isoprostane from fetal (placenta) and maternal (adipose tissue and skeletal muscle) tissues obtained from normal pregnant women and women with GDM. These data are consistent with the hypothesis that oxidative stress may be involved in the progression and/or pathogenesis of GDM.
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PMID:Release of proinflammatory cytokines and 8-isoprostane from placenta, adipose tissue, and skeletal muscle from normal pregnant women and women with gestational diabetes mellitus. 1553 21

Intra-amniotic lipopolysaccharide (LPS) causes an acute inflammatory response and cardiac dysfunction in fetal mice. We hypothesized that the placenta protects the fetus against maternally administered bacterial toxins, delaying the onset of a fetal inflammatory response and vascular compromise. At 14 to 15 days of gestation, DBA mice were randomized to receive LPS (2.4 mg/kg) or vehicle intraperitoneally. Doppler ultrasonography of fetal cardiovascular hemodynamics was performed before and 6 hours after maternal LPS. Six hours after the LPS, maternal serum concentrations of tumor necrosis factor-alpha and interleukin (IL)-6 (P < 0.05) were increased. Placenta showed severe maternal vascular dilatation and congestion. The expressions of tumor necrosis factor-alpha, IL-1alpha, and IL-6 (P < 0.05) were increased, and the expression of Toll-like receptor 4 was constitutive in placenta. The expression of Toll-like receptor 2 increased (P < 0.05) and was detected in labyrinthine macrophages. No inflammatory activation was found in fetal tissues, and amniotic fluid revealed no significant increase in cytokines. The ultrasonographic examination demonstrated increased fetal cardiac afterload after LPS, with 65% of the fetuses exhibiting atrioventricular valve regurgitation. In conclusion, maternal inflammatory insult activates placental labyrinthine macrophages leading to an acute increase in placental vascular resistance and fetal cardiac dysfunction without an inflammatory response in fetus.
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PMID:Mechanism of acute fetal cardiovascular depression after maternal inflammatory challenge in mouse. 1592 Jan 44

Up-regulation of pro-inflammatory cytokines, cyclooxygenase (COX-2) and prostaglandins is a critical factor driving human term labour and inflammation-associated preterm labour. Nuclear factor kappa B (NF-kappaB) is activated in response to a number of inflammatory mediators, including cytokines and lipopolysaccharide (LPS). The aim of this study was (i) to investigate if TNF-alpha and LPS activate the NF-kappaB pathway; and (ii) to use short interfering RNA (siRNA) against inhibitor kappaB kinase (IKK)-beta to confirm the role of the NF-kappaB pathway in the regulation of pro-inflammatory mediators in human placental JEG-3 cells. JEG-3 cells (3 independent experiments) were (i) incubated in the presence or absence of 10 microg/ml LPS or 20 ng/ml TNF-alpha, or (ii) transfected with 100 nM IKK-beta siRNA. Incubation of JEG-3 cells with LPS and TNF-alpha increased the expression of cytoplasmic IKK-beta and phosphorylated IkappaB-alpha, and nuclear NF-kappaB proteins p50 and p65. This was associated with a concurrent increase in COX-2 protein, and IL-6 and PGF2alpha release from JEG-3 cells. Treatment of cells with BAY 11-7082 at 50 microM significantly inhibited basal, LPS- and TNF-alpha-induced NF-kappaB and COX-2 expression, and IL-6 and PGF2alpha release. Transfection of JEG-3 cells with IKK-beta siRNA significantly decreased IL-6 and PGF2alpha release. The data presented in this study demonstrate that pro-inflammatory mediators regulate the NF-kappaB transcription pathway in human JEG-3 cells, and the IKK-beta/NF-kappaB pathway is a regulator of inflammatory mediators in placental JEG-3 cells.
Placenta
PMID:Lipopolysaccharide and TNF-alpha activate the nuclear factor kappa B pathway in the human placental JEG-3 cells. 1612 89

Mechanisms of HIV-1 in utero mother-to-child transmission (MTCT) protection provided by AZT are not completely understood. The placental cytokine network is involved in the control of HIV-1 in utero transmission but the effect of AZT on this network is unknown. To evaluate the effects of AZT on placental cytokine expression, the chorionic villi from HIV-1 uninfected women term placentae were cultured with 0, 100, and 2,000 ng/ml AZT. Tissue fragments were harvested at days 1, 4, and 7 to determine the level of cytokine mRNA by real-time RT-PCR. The viability and morphology of the placental histocultures were monitored by the expression of beta-human chorionic gonadotropin (beta-hCG) gene, lipopolysaccharide (LPS) activation, and microscopic examination. AZT at 2,000 ng/ml significantly down-regulated TNF-alpha mRNA expression at day 1 and day 4, but had no effect on beta-hCG, stromal cell-derived factor 1 (SDF-1), and IL-10 gene expression. AZT did not induce any deleterious impact on placental tissue structure. Furthermore, activation of chorionic villi by LPS for 24 h up-regulated IL-10 and TNF-alpha mRNA expression. Down-regulation of TNF-alpha mRNA could represent a mechanism through which AZT can decrease the risk of HIV-1 MTCT, in addition to its direct effect on HIV-1 replication.
Placenta
PMID:Down modulation of TNF-alpha mRNA placental expression by AZT used for the prevention of HIV-1 mother-to-child transmission. 1635 28

Chorioamnionitis increases the risk of preterm labour and is associated with adverse neonatal outcomes including cerebral palsy. Tumour necrosis factor-alpha (TNF-alpha) derived from the gestational tissues (placenta, fetal membranes and maternal decidua) is thought to play a pivotal role in the induction of cytokine response in chorioamnionitis. Tumour necrosis factor-alpha converting enzyme (TACE) is essential for the release of TNF-alpha. Our aim was to determine whether the expression of TACE is increased in human gestational tissues from pregnancies complicated by chorioamnionitis, and whether lipopolysaccharide (LPS) causes increased expression of TACE in the human gestational tissues in vitro. The immunostaining of TACE was generally more intense, in particular in the syncytiotrophoblast and stromal cells, in villous samples from pregnancies complicated by chorioamnionitis than those from normal pregnancies. Increased immunoreactivity of TACE was also noted in the amnion and choriodecidua. In parallel, there was an increased infiltration of monocytes/macrophages within the villous stroma and choriodecidua. As a complement to our in vivo findings, LPS significantly increased the levels of mRNA and protein of TACE in a dose-dependent response in villous and fetal membrane explant cultures. Together, our results imply a potential role of TACE in the pathogenesis of chorioamnionitis.
Placenta
PMID:Tumour necrosis factor-alpha converting enzyme in human gestational tissues from pregnancies complicated by chorioamnionitis. 1637 86

Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) induced immune responses, which may contribute to preterm labor associated with intraamniotic gram-negative bacterial infections. The study objective was to investigate gestational age and LPS-induced changes in TLR4 subcellular localization within amniotic epithelium, the first line of host defense against intraamniotic bacteria. TLR4 localization in amniotic epithelium was assessed using immunohistochemistry on 24 placentas of different gestational ages: first trimester (n=6), second trimester (n=6), and third trimester (n=12). Immunofluorescence was used to determine TLR4 localization following ex vivo LPS stimulation of amnion from women undergoing cesarean section without labor at term. TLR4 was expressed in the cytoplasm of amniotic epithelium starting at 9weeks with apical polarization by 25weeks gestation. TLR4 localization to the basal membrane was significantly associated with chorioamnionitis (p=0.01). After LPS stimulation, TLR4 was expressed sequentially within the apical membrane, cytoplasm, and finally in the basal cellular compartment. This suggests that TLR4 expression in amniotic epithelium is poised to monitor amniotic fluid for pathogens. TLR4 translocation to the basal membrane may decrease LPS signaling early in an infection, but allow the amniotic epithelium to remain competent to invasive or intracellular bacteria.
Placenta
PMID:LPS induces translocation of TLR4 in amniotic epithelium. 1705 75

Haem oxygenase-1 (HO-1) is an inducible enzyme that catalyses the rate-limiting step in the degradation of haem to biliverdin, carbon monoxide and iron. There is increasing evidence that HO plays important roles in the cellular defence against oxidative stress and the deleterious effects of pro-inflammatory cytokines. In the present study, we investigated the effects of lipopolysaccharide (LPS) on the expression of HO-1 in mouse placenta. When a single dose of LPS (75 microg/kg, i.p.) was administered to the pregnant mice, the expression of HO-1 in mouse placenta was markedly increased at 12 h after LPS treatment and remained elevated up to 48 h after LPS administration. The expression of HO-2, the constitutive form, did not change at the various time points observed. LPS-induced up-regulation of placental HO-1 was blocked after the pregnant mice were pre-treated with alpha-phenyl-N-t-butylnitrone (PBN), a free radical spin trapping agent. Correspondingly, PBN pre-treatment significantly inhibited LPS-induced lipid peroxidation and glutathione (GSH) depletion in mouse placenta. Furthermore, pentoxifylline (PTX), an inhibitor of tumour necrosis factor alpha (TNF-alpha) synthesis, also significantly attenuated LPS-induced up-regulation of placental HO-1. However, aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS), had little effect on LPS-induced up-regulation of HO-1 in mouse placenta. Taken together, these results indicate that LPS up-regulates the expression of HO-1 in mouse placenta. LPS-induced up-regulation of placental HO-1 is probably mediated, at least in part, by reactive oxygen species (ROS) and TNF-alpha, rather than nitric oxide.
Placenta
PMID:Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta. 1756 Jun 46


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