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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was developed by stimulation of the celiac ganglion with lipopolysaccharide (LPS) in pregnant rabbits. The renal and hepatic blood flow were measured after stimulation of the celiac ganglion with 10 microL (group 1), 100 microL (group II) and 300 microL (group III) of LPS (10 mg/mL conc.) and with 100 microL of normal saline (group IV). The bifurcation of the abdominal aorta was also stimulated with 300 microL of LPS (group V). A control experiment was also done in this study (group VI). Histopathological studies of kidney and liver tissue were also performed in this protocol. A significant reduction in renal and hepatic blood flow was observed in pregnant rabbits with the times and dosage dependent on stimulation of the celiac ganglion by LPS. Stimulation of the bifurcation of the abdominal aorta with LPS could not produce any changes in renal and hepatic blood flow. Preeclampsia-like histologic changes of kidney and liver tissue were also observed. These results suggest that exogenous stimulation of the celiac ganglion causes decreased renal and hepatic blood flow, resulting in preeclampsia-like histologic changes of kidney and liver in pregnant rabbits.
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PMID:Decreased renal and hepatic blood flow with preeclampsia-like histologic changes was obtained by stimulation of the celiac ganglion with LPS. 951 35

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.
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PMID:Effect of hypoxia, oxidative stress and lipopolysaccharides on the release of prostaglandins and cytokines from human term placental explants. 1131 28

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopolysaccharide (LPS, endotoxin) in mice. Pregnancy enhanced the LPS-induced production of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although adrenergic receptors are important regulators of cytokine production in non-pregnant mice, the alpha(2)- and the beta-adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with severe endotoxemia. These data may explain how excessive activation of the non-specific immune responses during pregnancy can contribute to the increased severity of some maternal diseases, including septic shock, and can be an important pathophysiological factor in disseminated intravascular coagulation or preeclampsia.
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PMID:Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice. 1169 56

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.
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PMID:Modulation of prostacyclin and thromboxane secretion by cytotrophoblasts from normal and pre-eclamptic human pregnancies. 1236 79

Increased fgl2 prothrombinase activity in maternal decidua and fetal trophoblasts may trigger abortions by proinflammatory cytokines induced by bacterial lipopolysaccharide (LPS) in mice and is implicated in human recurrent miscarriages and pre-eclampsia. Defining the physiological and pathological role of the fgl2/fibroleukin gene required an fgl2-knockout mouse and data on normal pattern of fgl2 expression during pregnancy. Expression of fgl2 protein was determined by immunostaining with specific antibody. Fgl2 knockout mice were generated and typed by PCR for presence of the altered gene. Immunostaining of timed CBAxDBA/2 mouse matings in a low-abortion-rate colony showed a distinct pattern of development of fgl2 protein expression in maternal decidua, and in embryonic tissues in early pregnancy. Outbred (mixed background) heterozygous fgl2 +/-x+/- matings with a similar low abortion rate showed selective occult loss of both +/- and, to a greater extent, -/- embryos prior to gestation day 11.5, in association with haemorrhage at the anti-mesometrial pole of fgl2-deficient embryo. LPS injected on day 6.5 caused classical abortions at mid-pregnancy in fgl2 +/+x+/+ matings, but not -/-x-/- matings. Physiological expression of fgl2 in fetal trophoblast may prevent occult loss in early pregnancy, along with other coagulation factors, but fgl2 expression is required for LPS to induce abortion pathology.
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PMID:The fgl2 prothrombinase/fibroleukin gene is required for lipopolysaccharide-triggered abortions and for normal mouse reproduction. 1474 94

Observations that the innate arm of the immune system is upregulated in pregnancy have highlighted the need for methods of isolating pure populations of monocytes for studies into pregnancy and pre-eclampsia without activating them during the isolation process. Density gradient centrifugation using iodixanol is a useful method for isolating relatively pure populations of unactivated monocytes from human blood but has not been validated in pregnant subjects. We compared the ability of monocytes isolated from pregnant women by density gradient centrifugation using iodixanol (n=6) with monocytes isolated by countercurrent centrifugal elutriation (n=6) in terms of their ability to produce interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) under basal conditions and after stimulation with bacterial lipopolysaccharide (LPS). Under basal conditions, monocytes isolated by density gradient centrifugation produced low amounts of IL-6 and MCP-1. Production of IL-6 and MCP-1 after stimulation of the monocytes with LPS was much greater (p<0.01). There was no statistically significant difference between the two methods in terms of stimulated levels of either cytokine.
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PMID:Isolating pure populations of monocytes from the blood of pregnant women: comparison of flotation in iodixanol with elutriation. 1554 Dec 90

Pre-eclampsia is associated with inadequate cytotrophoblast invasion and remodeling of the uterine spiral arterioles, as well as by an aberrant maternal immune response. This study determined the effect of activated macrophages and one of its products, tumor necrosis factor (TNF)-alpha, on cytotrophoblast invasiveness. Coculture with human lipopolysaccharide-activated macrophages decreased the ability of immortalized HTR-8/ SVneo human trophoblast cells to invade through reconstituted extracellular matrix (P < 0.05). This effect of activated macrophages on trophoblast invasiveness was paralleled by abrogation of a 55-kDa caseinolytic activity corresponding to prourokinase plasminogen activator (pro-uPA) and an increased secretion of plasminogen activator inhibitor 1 (PAI1), as determined by gel zymography and ELISA, respectively. Coculture with nonactivated macrophages did not significantly affect trophoblast invasiveness or pro-uPA and PAI1 secretion. Activated macrophages secreted detectable levels of TNF, and administration of exogenous TNF significantly decreased trophoblast invasiveness (P < 0.05), increased the secretion of PAI1 (P < 0.01), and completely inhibited the pro-uPA-associated caseinolytic activity by binding to the TNF receptor 1. Moreover, addition of up to 10 ng/ml of TNF did not increase the rate of apoptosis in HTR-8/SVneo cells. Finally, the increased secretion of PAI1 by trophoblast cells cocultured with activated macrophages was significantly inhibited when a neutralizing anti-TNF antibody was added to the cocultures. These results suggest that the aberrant presence of activated macrophages around uterine vessels may contribute to inadequate trophoblast invasion and remodeling of the uterine spiral arterioles. Thus, the presence of activated macrophages may be important in the etiology of pre-eclampsia.
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PMID:Activated macrophages inhibit human cytotrophoblast invasiveness in vitro. 1580 Jan 79

The maternal syndrome preeclampsia is characterized by a generalized inflammatory response with activation of circulating leukocytes and altered levels of inflammatory cytokines. We hypothesized that one potential source of inflammatory cytokines during preeclampsia is the circulating maternal monocytes. By using flow cytometry, we found that the spontaneous intracellular synthesis of IL-1beta, IL-6, and IL-8 in monocytes of preeclamptic women was higher than in normal pregnant and non-pregnant women. The highest levels of cytokines were detected in women with the most abnormal laboratory values. When stimulated with lipopolysaccharide (LPS), the percentage of IL-1beta+ monocytes was lower in preeclampsia (72.6% +/- 8.2 SEM) than in normal pregnancy (90.7% +/- 2 SEM) (P = 0.03) and non-pregnant women (92.5% +/- 1.4 SEM) (P = 0.04) suggesting that monocytes from preeclamptic patients cannot be further stimulated. These results indicate that maternal circulating monocytes represent a source of inflammatory cytokines during preeclampsia.
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PMID:Monocytes of preeclamptic women spontaneously synthesize pro-inflammatory cytokines. 1633 93

Periodontal disease is a common infectious disease in women of reproductive age. The disease is often not diagnosed and in studies of over 10 000 women has been associated with preterm birth, small for gestational age newborns, and preeclampsia. It has been shown in a smaller number of women that treatment of periodontal disease may reduce the rate of preterm birth. The pregnancy complications of periodontal disease may be due to lipopolysaccharide from the periodontal pockets inciting prostaglandin pathways controlling parturition. Three large randomized controlled trials of treatment of periodontal disease are underway and may provide confirmation of the importance of periodontal disease in causing complications of pregnancy.
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PMID:Periodontal disease and adverse pregnancy outcomes. 1696 19

Trophoblast invasion and modification of the spiral arterioles are essential for the establishment of adequate uteroplacental blood flow during pregnancy. However, such vascular remodeling is deficient in preeclampsia. This disease is also associated with increased maternal levels of circulating proinflammatory cytokines such as tumor necrosis factor (TNF) and reduced levels of immunoregulatory cytokines such as interleukin 10 (IL10). We have previously shown that activated macrophages inhibit trophoblast invasiveness in vitro. The present study demonstrates that IL10 interferes with the invasion-inhibitory effect that activated macrophages exert on trophoblast cells. Co-culture experiments revealed that human lipopolysaccharide (LPS)-activated macrophages inhibited the ability of immortalized HTR-8/SVneo human trophoblast cells to invade through reconstituted extracellular matrix. This effect of activated macrophages on trophoblast invasiveness was paralleled by decreased expression of urokinase plasminogen activator receptor (PLAUR) on the surface of trophoblast cells, and by increased secretion of plasminogen activator inhibitor type 1 (SERPINE1). Exposure of LPS-treated macrophages to IL10 prior to co-culture prevented their ability to inhibit trophoblast invasion, PLAUR expression, and to stimulate SERPINE1 secretion. Interleukin 10 prevented macrophage activation by LPS as determined by the lack of secretion of TNF in the culture medium, and a neutralizing TNF antibody completely blocked the effect of macrophages on trophoblast invasion. These results indicate that decreased circulating levels of IL10 associated with preeclampsia may contribute to inadequate trophoblast invasion and remodeling of the uterine spiral arterioles.
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PMID:Coordinated regulation of human trophoblast invasiveness by macrophages and interleukin 10. 1715 53


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