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

Mouse resident peritoneal macrophages stimulated in vitro by purified bacterial lipopolysaccharide (LPS) produced both prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), the latter detected as its stable metabolite, 6-keto PGF1 alpha. Maximum production, induced in each case by 1 ng/ml purified LPS, was in the range of 10(-7)M for PGI2 and 3 x 10(-8)M for PGE2. A quantitatively similar increase in intracellular levels of macrophage cyclic AMP (measured on a whole cell basis), with a similar duration of effect, was stimulated by PGE2 and PGI2; however, only PGE2 had a negative regulatory effect on macrophage activation for tumor cell killing. These data confirm that more than a whole cell increase in the concentration of cyclic AMP is needed to shut off nonspecific tumor cell killing mediated by LPS-activated resident peritoneal macrophages.
 ...
PMID:Regulation of macrophage-mediated tumor cell killing by prostaglandins: comparison of the effects of PGE2 and PGI2. 630 Sep 68

The secretion of the phospholipase A2-inhibitor macrocortin and the binding of dexamethasone were studied in suspensions of rat peritoneal macrophages. Corticosteroid-induced macrocortin secretion was specific for glucocorticoids and did not occur in response to glucocorticoid antagonists or other steroids or in response to non-steroid macrophage activators (formyl-methionyl-leucyl-phenylalanine f-MLP), the calcium ionophore A23187, phorbol myristate acetate (PMA) and lipopolysaccharide-E.-coli(LPS) ). The apparent potency of competition by secretory glucocorticoids for dexamethasone binding to the macrophage parallelled their ability to induce secretion, implying that these binding sites represent the receptors by which macrocortin secretion is initiated. Agents which interfere with microtubule assembly (colchicine, vinblastine and trimethylcolchicinic acid) and prostacyclin and dibutyryl cyclic AMP inhibit macrocortin secretion. Inhibition studies of glucocorticoid-induced macrocortin secretion also suggest dependence upon metabolic energy, a source of Ca2+ and proteolysis and glycosylation prior to secretion.
 ...
PMID:Specificity and inhibition of glucocorticoid-induced macrocortin secretion from rat peritoneal macrophages. 631 16

The serous membranes of the rabbit peritoneal cavity are tissues in which cyclo-oxygenase and lipoxygenase pathways of arachidonate metabolism can be studied simultaneously. After elaboration of the optimum conditions, the metabolism of two concentrations of arachidonic acid (AA) was studied in the presence and absence of endotoxin lipopolysaccharide (LPS) from E. coli O127:B8 (0.1 and 1.0 mg/ml). LPS suppressed the formation of radiolabelled cyclo-oxygenase products (predominantly prostacyclin) at the lower concentration of exogenous AA (0.8 microM), but not at the higher substrate concentration (34.5 microM). The biosynthesis of lipoxygenase metabolites, i.e. monohydroxyeicosatetra-enoic acids (HETEs), was not influenced by LPS. These findings can be explained by an enhanced release of endogenous AA in the prostacyclin forming mesothelial cells in the presence of LPS. Measurements of the endogenous biosynthesis of prostacyclin supported this assumption.
 ...
PMID:Influence of endotoxin on arachidonate metabolism in isolated rabbit peritoneum. 641 18

Recent reports have shown that prostaglandin E2 (PGE2) is able to suppress lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-alpha (TNF-alpha). In the present study we compared PGE2 with prostacyclin (PGI2) analogs in their potency to influence LPS-stimulated production of interleukin-1 beta (IL-1 beta) and TNF-alpha by human mononuclear cells (MNC). Our results show, that the stable analogs of PGI2, iloprost and cicaprost, markedly suppress TNF-alpha synthesis in LPS-stimulated MNC without effect on IL-1 beta production. Although there was no significant difference in maximal suppression of TNF-alpha, iloprost and cicaprost reached suppression to 50% of control at 20-fold lower concentrations than PGE2. The ID50 for iloprost and cicaprost were 8 nM and 5 nM, respectively, compared to 125 nM for PGE2. Moreover, the prostacyclin analogs as well as PGE2 suppressed LPS-induced production of TNF-alpha in Mono Mac 6 cells, a permanent human cell line with characteristics of mature monocytes. Suppression of TNF-alpha synthesis by cicaprost and PGE2 is probably mediated by an increased intracellular cAMP formation. We were able to show elevated cAMP levels with 1 microM and 10 microM of PGE2 and cicaprost in this system. The suppression of TNF-alpha synthesis may add to the beneficial effects of iloprost reported in animal models of acute respiratory distress syndrome (ARDS) and may offer a therapeutic approach in TNF-alpha mediated pathologic processes.
 ...
PMID:Prostacyclin analogs suppress the synthesis of tumor necrosis factor-alpha in LPS-stimulated human peripheral blood mononuclear cells. 750 98

Previous studies have shown that prostacyclin analogs can inhibit the expression of tissue factor (TF) procoagulant activity by human monocytes. The present studies have investigated this phenomenon further, by using a plasma coagulation assay to measure cellular TF activity, an immunoassay to measure TF antigen and reverse transcription/polymerase chain reaction with appropriate oligomer primers to measure TF mRNA. Iloprost and cicaprost inhibited lipopolysaccharide-induced increases in TF activity, antigen and mRNA (50% inhibition, 2-8 nM), with no apparent effect on TF mRNA stability. These agents therefore act at or before the level of transcription of the TF gene. The analogs were more potent inhibitors of tumor necrosis factor-alpha synthesis (50% inhibition at 334 +/- 40 pM cicaprost or 846 +/- 182 pM iloprost) and extraordinarily potent when combined with a phosphodiesterase inhibitor (50% inhibition at 101 +/- 31 pM iloprost in the presence of 20 microM isobutylmethylxanthine). Iloprost and cicaprost were less potent in inhibiting the synthesis of interleukin-1 beta (50% inhibition, 50-100 nM). Cicaprost inhibited lipopolysaccharide-induced increases in mRNA levels for TF, tumor necrosis factor-alpha and interleukin-1 beta; differential potency was again observed. We conclude that these three important monocyte functions can be down-regulated by prostacyclin analogs, and with differential sensitivity. Furthermore, the extreme sensitivity of tumor necrosis factor-alpha synthesis to inhibition suggests that such inhibition may be a major physiological function of prostacyclin itself.
 ...
PMID:Effects of prostacyclin analogs on the synthesis of tissue factor, tumor necrosis factor-alpha and interleukin-1 beta in human monocytic THP-1 cells. 752 28

In this study we have investigated the correlation between prostaglandin generation and the L-arginine:nitric oxide (NO) pathway in the lung of rats challenged with lipopolysaccharide. We found that in rats treated with L-arginine, the amount of prostacyclin, measured as 6-keto-PGF1 alpha, was significantly increased. Conversely in rats treated with NG-nitro-L-arginine methyl ester the production of 6-keto-PGF1 alpha by lung was significantly decreased. Chopped lungs that had been removed from rats challenged with lipopolysaccharide and were incubated overnight with L-arginine or nitric oxide inhibitors, NG-nitro-L-arginine methyl ester or NG-monomethyl-L-arginine, released respectively increased or decreased amount of 6-keto-PGF1 alpha. These results suggest that, in the rat, lung endogenous nitric oxide may modulate prostanoid production.
 ...
PMID:Nitric oxide modulates prostacyclin biosynthesis in the lung of endotoxin-treated rats. 752 84

We examined the effects of E. coli lipopolysaccharide (LPS) and synthetic analogs of lipid A, a bioactive moiety of LPS, on the prostacyclin (PGI2) production by young and old human endothelial cells in vitro. PGI2 production by endothelial cells has been shown to decrease during in vitro cellular senescence as well as in vivo. LPS and all the analogs tested in this study did not stimulate PGI2 production by young endothelial cells more than twofold. However, LPS and the majority of the lipid A analogs examined stimulated the PGI2 production by old cells more than twofold (approximately two- to sixfold). These results indicate that the responses to certain stimuli sometimes differ markedly between young and old cells, and this should be carefully considered when evaluating the biological effects of various compounds. Furthermore, these results suggest that certain synthetic lipid A analogs can be used as drugs to prevent some age-related vascular diseases.
 ...
PMID:Elevated promotion of prostacyclin production by synthetic lipid A analogs in aged human endothelial cells in culture. 759 96

Plasma cytokine levels are enhanced in aged animals and in elderly people. Vascular cells are known to be both targets and sources of cytokines. To investigate the effect of aging on vascular cytokine synthesis, we studied tumor necrosis factor (TNF), interleukin-6 (IL-6), and prostacyclin (PGI2) production by the arterial wall using organoid culture of aorta from 10- (n = 8) and 30-mo-old (n = 8) rats, after activation by lipopolysaccharide (LPS). Biological activity of TNF and IL-6 was measured in supernatant from incubated vessels. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of PGI2, a secondary inflammatory mediator, was measured using enzyme immunoassay. In the absence of LPS, TNF production was undetectable in most animals and was not significantly increased in the aged group. By contrast IL-6 and 6-keto-PGF1 alpha productions, in the absence of LPS, were significantly greater in 30- (8,140 +/- 1,350 U/micrograms DNA and 23.2 +/- 6.4 ng/micrograms DNA, respectively) than in 10-mo animals (3,060 +/- 350 U/micrograms DNA and 8.4 +/- 1.6 ng/micrograms DNA, P < 0.01 and P < 0.05, respectively). LPS-induced production of TNF, IL-6, and 6-keto-PGF1 alpha was significantly increased in old rats, being increased respectively by 3.2-, 3.5-, and 2.4-fold at 1 ng/ml LPS, compared with the production in young rats. Because TNF and IL-6 are capable of regulating vascular cell function such as proliferation protein synthesis and contractility, these cytokines might play a major role in age-related remodeling of arteries and age-related vascular diseases.
 ...
PMID:Increased production of tumor necrosis factor and interleukin-6 by arterial wall of aged rats. 761 79

We determined the efficacy of continuous arteriovenous hemofiltration (CAVH) in removing tumor necrosis factor (TNF), thromboxane A2, and prostacyclin, and in improving survival in endotoxemia. Twelve rats were given 10 mg/kg of E. coli 0:127:B8 lipopolysaccharide. Fifteen min later, the rats were randomized to ultrafiltered or non-ultrafiltered groups. Blood and ultrafiltrate were collected for TNF, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). After 4 hr, surviving rats were sacrificed. Five of 6 ultrafiltered and none of 6 non-ultrafiltered rats survived 4 hr. Plasma TxB2 > 1,000 pcg/ml and its rate of increase within the first 2 hr predicted death (P < 0.03). Ultrafiltration decreased the rate of rise in TxB2 (P < 0.04). Plasma TxB2 inversely correlated with TxB2 clearance by ultrafiltration. The concentration and rate of increase in TNF and 6-keto-PGF1 alpha did not predict survival. We conclude that CAVH improves short term survival in endotoxemia. Salutary effects appear to be due to thromboxane A2 removal.
 ...
PMID:Efficacy of continuous arteriovenous hemofiltration in endotoxic shock. 762 59

Prostacyclin analogues have been reported to inhibit the expression of tissue factor procoagulant activity in human monocytes, primarily by elevating intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP). The present studies have investigated whether prostacyclins can also inhibit tissue factor expression in endothelial cells. Iloprost, carbacyclin, and ciprostene had no effect on human umbilical vein endothelial tissue factor activity induced by lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), or interleukin-1 beta (IL-1 beta). Iloprost failed to elevate intracellular levels of cAMP, even when combined with a phosphodiesterase inhibitor. In contrast, forskolin increased endothelial cAMP and inhibited tissue factor expression. Conditioned medium from LPS-challenged monocytic THP-1 cells, which contained both TNF-alpha and IL-1 beta, induced endothelial cell procoagulant activity to levels 20-fold higher than those achieved in response to LPS alone. Iloprost abolished LPS-induced TNF-alpha secretion by THP-1 cells and inhibited IL-1 beta secretion by 45%. In keeping with this, iloprost reduced levels of TNF-alpha and IL-1 beta mRNA in LPS-challenged cells. Treatment of THP-1 cells with iloprost strongly inhibited the ability of conditioned medium to induce endothelial tissue factor expression, an effect that was mimicked by treating the medium with blocking antibodies to the cytokines. We conclude that although prostacyclin analogues do not directly suppress endothelial tissue factor expression due to their failure to elevate cAMP, they may do so indirectly by inhibiting the amplification produced by monocyte-derived cytokines.
 ...
PMID:Effects of prostacyclin analogues on human endothelial cell tissue factor expression. 768 94


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>