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)

The effects of pretreatment with prostaglandin E2 or the platelet-activating factor antagonist, CV-3988, on endotoxin-induced gastric damage, gastrointestinal plasma protein leakage, and systemic hypotension were examined in the rat. Endotoxic shock was induced by intravenous administration of lipopolysaccharide from Escherichia coli and was characterized by prolonged hypotension, gastrointestinal hyperemia and hemorrhage, and marked leakage of radiolabelled albumin into the interstitium and lumen of the gastrointestinal tract. Prostaglandin E2 (25-100 micrograms/kg i.v.) dose-dependently inhibited the hypotension and gastric damage induced by endotoxin. At the dose tested, CV-3988 (10 mg/kg i.v.) also significantly reduced endotoxin-induced hypotension and gastric damage. Both prostaglandin E2 (50 micrograms/kg) and CV-3988 reduced endotoxin-induced plasma protein leakage into the interstitium and lumen of the gastrointestinal tract, although there were differences in terms of the regions most affected by the two compounds. The results of the present study suggest that prostaglandin E2 and CV-3988 may have acted via a similar mechanism, possibly involving inhibition of a mediatory role of platelet-activating factor in endotoxic shock.
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PMID:Gastrointestinal plasma leakage in endotoxic shock. Inhibition by prostaglandin E2 and by a platelet-activating factor antagonist. 347 14

Exposure of rats to high concentrations of oxygen (greater than 95%) at 1 ATA pressure (101 kPa) is lethal within three days. Rats treated with a small dose of endotoxin are protected against these lethal effects of hyperoxia. Recently, we found that the lysine salt of acetylsalicylic acid antagonises this protective action of endotoxin. This suggests that prostaglandin metabolism plays an important role in the protective action of endotoxin against pulmonary oxygen toxicity. Therefore, we measured the plasma levels of 6KPGF1 alpha, a stable degradation product of prostacyclin (PGI2), PGE2 and thromboxane B2, the stable degradation product of thromboxane A2, in rats exposed to air or greater than 95% oxygen for 48 hours. We compared these with the plasma levels of rats treated with endotoxin (Salmonella typhimurium lipopolysaccharide 1 mg/kg) and exposed to air or greater than 95% oxygen for 48 hours. We found that exposure of rats to greater than 95% oxygen for 48 hours leads to a significant rise in the 6KPGF1 alpha levels. Rats exposed to greater than 95% oxygen for 48 hours and treated with endotoxin had significantly higher PGE2 and significantly lower 6KPGF1 alpha plasma levels than saline-treated rats exposed to greater than 95% oxygen for 48 hours.
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PMID:Endotoxin protection against pulmonary oxygen toxicity and plasma prostaglandin levels in the rat. 347 92

Mononuclear phagocyte populations and monocytes are able to produce, among numerous substances, a neutral protease, i.e. plasminogen activator (PA) and prostaglandins. Since it has been shown that prostaglandins (PGs) and particularly PGE2 could exert an inhibitory effect on PA production by macrophages, we have measured the in vitro production of PA and PGE2 by monocytes isolated from healthy donors. These monocytes were cultured either in the absence or the presence of various immunomodulators: lipopolysaccharide from E. coli, concanavalin A and RU 41740 or Biostim a broad spectrum immunostimulating agent isolated from Klebsiella pneumoniae (Cassenne Laboratories, France). The production of PGE2 was proportional to the number of monocytes per incubation, and at a given cell concentration varied greatly from one subject to another. When considering PGE2 productions, the type of the response to the different immunomodulators varied from subject to subject and ranged from stimulation to no effect, or even inhibition. Moreover, a statistically significant, inverse relationship exists between the spontaneous production of PGE2 and the effect of each immunomodulator. For a given subject, all agents always acted in the same way and there was an inverse relationship between the effects of the immunomodulators on plasminogen activator and PGE2 production.
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PMID:Regulation of prostaglandin E2 and plasminogen activator by various immunomodulators in human monocytes. 351 84

Bolus i.v. administration of 100 micrograms/kg of E. Coli lipopolysaccharide endotoxin (LPS) to adult male Munich-Wistar rats (N = 18) resulted in a progressive fall in RBF and GFR from 6.9 +/- 0.2 SE and 1.1 +/- 0.05 ml/min to minimal values at 50 minutes of 3.8 +/- 0.4 and 0.32 +/- 0.08 (P less than 0.05), respectively, without a fall in mean arterial pressure. At 50 minutes, renal cortical generation rates of PGE2 (1075 +/- 108 pg/mg tissue), 6 keto PGF1 alpha (221 +/- 41 pg/mg), and TxB2 (106 +/- 12 pg/mg) were significantly higher than those of vehicle-treated control rats (N = 10, PGE2 = 466 +/- 107, 6 keto PGF1 alpha = 94 +/- 3, and TxB2 = 35 +/- 3 pg/mg), and morphologic examination revealed normal histology with notable absence of leukocytes and platelets. Pretreatment of a third group of nine rats with TxA2 synthetase inhibitor UK-37.248 (dazoxiben, 10 mg/kg) selectively abolished the LPS-induced rise in TxB2 (29 +/- 3 pg/mg), but not PGE2 (837 +/- 62 pg/mg) or 6 keto PGF1 alpha (179 +/- 5 pg/mg), prevented the fall in RBF at 50 minutes (6.3 +/- 0.4 ml/min), and allowed for significant preservation of GFR (0.67 +/- 0.08 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Roles for thromboxane A2 and leukotrienes in endotoxin-induced acute renal failure. 353 51

Prostaglandin E2 (PGE2) and lipopolysaccharide (LPS) derived from E. coli were injected into the lateral cerebral ventricle of rabbits at 30 degrees C ambient temperature. The threshold core temperatures for ear cutaneous vasoconstriction (Thv) and shivering (Thsh) were determined by whole-body cooling with an intestinal thermode. Each threshold, as determined at the plateau phase of LPS fever and PGE2 hyperthermia respectively, were compared with the control values before LPS and PGE2 injection. Thsh was not changed by the injection of LPS, while Thv was increased. After PGE2 injection both Thsh and Thv were increased in comparison to their control levels. These changes paralleled the elevation of core temperature. The present study does not exclude prostaglandins as humoral mediators involved in some of the central processes generating fever, but suggest at the same time that there are additional properties of LPS fever for which prostaglandins do not account.
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PMID:Comparison of the action of prostaglandin with endotoxin on thermoregulatory response thresholds. 390 50

We have investigated the role of arachidonic acid metabolites in the regulation of interleukin-1 production by murine peritoneal macrophages. Indomethacin a potent inhibitor of prostaglandin synthesis caused a dose-dependent augmentation of lipopolysaccharide induced interleukin production (up to 7-fold at 5 microM). In contrast, lipoxygenase inhibitors, nordihydroguarietic acid and nafazatrom had no effect at doses that did not significantly decrease prostaglandin synthesis. Added to lipopolysaccharide stimulated cultures, PGE2 was also augmented by indomethacin but unlike lipopolysaccharide treated cultures was suppressed by nordihydroguarietic acid. These data suggest that arachidonate metabolites may be potent autoregulators of macrophage interleukin-1 production.
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PMID:Arachidonic acid metabolites regulate interleukin-1 production. 392 70

We demonstrated previously that rabbit alveolar macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) have markedly enhanced procoagulant activity (PCA), caused by increased production of a cell-associated tissue thromboplastin. The present study examined the role of arachidonic acid metabolites in modulating the expression of this PCA. Alveolar macrophages lavaged from normal rabbits were incubated in vitro with LPS, indomethacin, and purified prostaglandins, and the resultant PCA was measured. LPS stimulated a significant increase in macrophage PCA relative to unstimulated controls (p less than 0.01). Indomethacin suppressed the ability of LPS to stimulate PCA in a dose-related fashion. The addition of PGE2 or PGE1 reversed the suppressive action of indomethacin (p less than 0.01), whereas PGF2 alpha, PGD2, TXB2, and 6-keto PGF1 alpha had no such effect. PGE2 did not affect PCA unless the macrophages were also stimulated with LPS. A significant correlation (rs = 0.72, p less than 0.01) existed between the level of LPS-stimulated macrophage PCA and the corresponding amount of immunoreactive PGE2 released into the culture medium. The results of this study demonstrate that PGE is required for the LPS-mediated enhancement of rabbit alveolar macrophage-associated tissue thromboplastin and that PGE can stimulate the expression of PCA by appropriately conditioned cells.
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PMID:Prostaglandin E is required for the augmentation of procoagulant activity of LPS-stimulated rabbit alveolar macrophages. 658 Dec 28

Human monocytes from normal donors as well as breast or colon cancer patients were fractionated on five-step discontinuous bovine serum albumin (BSA) density gradients, and the monocytes from each fraction were allowed to mature into macrophages during a 5 day incubation period. The macrophages were then examined both for their ability to kill tumor cells after activation with lipopolysaccharide (LPS) and the quantity of prostaglandin E2 (PGE2) synthesized. When the macrophages obtained from normal donors were fractionated, fractions 2 and 4 which comprised 58% of the total cell population, were cytotoxic for tumor cells. In contrast, when the macrophages from breast cancer patients were fractionated, only the high density cells found in fraction 4 were cytotoxic. It is also conceivable that since fraction 4 comprises only 26% of the total macrophages recovered, this may be the reason unfractionated macrophages from breast cancer patients are unable to kill tumor cells. When the colon cancer patients' macrophages were fractionated on BSA density gradients, fractions 1, 2 and 4, which comprised 79% of the total cell population, were cytotoxic for tumor cells. Prostaglandin E2 synthesis was also analyzed and it was found that fraction 3 consistently synthesized increased quantities of PGE2 when compared with the other three fractions. Furthermore, since fraction 3 was non-cytotoxic for tumor cells, it is conceivable that the increased synthesis of PGE2 by fraction 3 rendered these macrophages non-cytotoxic.
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PMID:Separation of macrophages on discontinuous bovine serum albumin (BSA) density gradients: cytotoxic effects of fractionated cells from normal donors and cancer patients. 659 30

Spleen cells of diabetes-prone BB Wistar rats were found to generate excessively low proliferative responses, and interleukin 2 (IL-2) levels in response to T-dependent mitogens. This abnormality was not due solely to abnormal T cell numbers since: (a) addition of BB spleen cells of BB splenic macrophages to normal major histocompatibility complex (MHC)-matched Wistar Furth (WF) spleen cells resulted in severe suppression of concanavalin A (Con A)-, phytohemagglutinin (PHA)-, and pokeweed mitogen (PWM)-mediated proliferation, and IL-2 production; (b) macrophage depletion from BB spleen cells, but not B cell or T cell depletion, removed completely the suppressive effects of BB cells on WF cells; (c) macrophage depletion greatly enhanced the response of BB lymphocytes to T-dependent mitogens. Although suppressor macrophages could also be found in the spleen of WF control rats they were present in much smaller numbers than in the spleen of BB rats. The suppressive effect of BB macrophages was partially reduced by addition of the prostaglandin synthetase inhibitor indomethacin to cultures. Furthermore, indomethacin (but not catalase or PMA) considerably augmented IL-2 secretion of Con A-stimulated BB spleen cells, but had little effect on WF spleen cells. In contrast, prostaglandins E1 and E2 (PGE1 and PGE2) suppressed IL-2 production. While IL-2 secretion was severely depressed in BB rats unstimulated and lipopolysaccharide (LPS)-stimulated IL-1 secretion by splenic macrophages was normal. BB macrophages did not inactivate IL-2. Low IL-2 production and macrophage-mediated suppression were features of all BB rats tested.
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PMID:Immune dysfunction in diabetes-prone BB rats. Interleukin 2 production and other mitogen-induced responses are suppressed by activated macrophages. 660 15

The serum-free spent medium of lipopolysaccharide-activated rabbit peritoneal macrophages contains a proteinaceous factor that stimulates the synthesis of PGE2 in rabbit articular chondrocytes. Synthesis of this factor by macrophages is inhibited by cycloheximide. Stimulation of PGE2 in chondrocytes is detected after a four-hour exposure to the macrophage factor and is completely abolished by the addition of either cycloheximide or indomethacin to the chondrocyte cultures. The macrophage derived factor has an apparent molecular weight of 30,000, is heat stable and not inactivated upon reductive alkylation or on treatment with phenylglyoxal. Activity is partially destroyed upon treatment with acid (pH 2.0) and upon trypsin treatment.
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PMID:Stimulation of prostaglandin E2 synthesis in chondrocytes by a factor derived from activated macrophages. 696 Mar 88


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