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 effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids.
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PMID:Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. 128 71

We have recently shown that cultured endothelial cells produce kinins that can stimulate endothelial nitric oxide (NO) production in an autocrine manner. Because both the kallikrein-kinin system and the L-arginine/NO pathway have been implicated in the pathogenesis of septic shock, we investigated the possible involvement of endothelium-derived kinins in the response of cultured endothelial cells to bacterial lipopolysaccharide (LPS). In primary cultures of human umbilical vein and porcine aortic endothelial cells, LPS (0.3 to 3 micrograms/ml) induced significant concentration-dependent increases in cyclic GMP and 6-keto-PGF1 alpha, both of which were abolished in the presence of the selective bradykinin B2-receptor antagonist HOE 140 (0.1 microM). These LPS-induced increases in cyclic GMP and 6-keto-PGF1 alpha were short lived, being maximal after 5 min but were not apparent after 60 min. In parallel with these effects, LPS (30 micrograms/ml) induced a distinct, HOE 140-sensitive increase in the intracellular calcium concentration of human endothelial cells loaded with indo-1. In summary, these data suggest that the release of endothelium-derived kinin and subsequent stimulation of endothelial cells, followed by the enhanced production of NO and prostacyclin (PGI2), are implicated in the immediate hypotension induced by LPS in vivo.
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PMID:Endothelium-derived kinins account for the immediate response of endothelial cells to bacterial lipopolysaccharide. 128 49

The effect of recombinant tumor necrosis factor and other cytokines stimulated by LPS (lipopolysaccharide), on the release of endothelial-derived relaxing factor and of prostacyclin was investigated using freshly harvested endothelial cells attached to plastic microcarrier beads. The results show that the cytokines failed to interfere with the release of EDRF and prostacyclin under the conditions of these experiments.
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PMID:The effect of immune mediators (cytokines) on the release of endothelium-derived relaxing factor (EDRF) and of prostacyclin by freshly harvested endothelial cells. 131 94

Arachidonate metabolism was examined in rats with experimentally induced acute and chronic liver injuries. Acute liver injury was induced by a single administration of D-galactosamine (D-Galn) and lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Chronic liver injury was produced by several administrations of CCl4 for 5 weeks. Non-parenchymal liver cells from rats with D-Galn/LPS-induced acute liver injury produced prominently leukotriene B4 and 5-hydroxy-arachidonic acid which were hardly synthesized by the normal rat liver. No apparent changes were observed in the arachidonate metabolism of the non-parenchymal cells of the acute CCl4-injured liver. In chronic liver injury, the production of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostaglandin I2, by the non-parenchymal cell fraction was significantly enhanced in contrast with the fixed amount of the other arachidonate metabolites. These results suggested the arachidonate metabolism by non-parenchymal liver cells might change according to the pathogenesis of the liver disease.
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PMID:Arachidonate metabolism in D-galactosamine or carbon tetrachloride-induced acute and chronic liver injuries in rats. 133 Jul 97

Tumor necrosis factor (TNF), a protein produced in large quantities by endotoxin-activated macrophages, has been implicated as an important mediator of the lethal effect of endotoxin. A stable prostacyclin analogue (iloprost) was investigated for its ability to interfere with TNF secretion of lipopolysaccharide (LPS)-stimulated macrophages. It could be demonstrated by bioassays that LPS-induced TNF production was suppressed in a dose-dependent manner when macrophages were treated with iloprost at the time of LPS stimulation. Northern blot analysis revealed that iloprost inhibited TNF production at the transcription level. In vivo, endotoxin-induced mortality rates in galactosamine-sensitized mice could be significantly (P less than .05) reduced by iloprost administration. It is assumed that prostacyclin modulates endotoxin-induced and TNF-mediated inflammation in septic shock.
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PMID:Inhibition of endotoxin-induced macrophage tumor necrosis factor expression by a prostacyclin analogue and its beneficial effect in experimental lipopolysaccharide intoxication. 137 36

Interleukin-1 receptor antagonist (IRA) is a secretory product of human monocytes or related cell lines that acts as a pure interleukin-1 (IL-1) antagonist in several bioassays. IRA administration was reportedly a life-saving intervention in rabbits injected with lethal doses of bacterial lipopolysaccharide (LPS). We report the inhibitory effect of IRA on three distinct types of vascular responses to IL-1 in rabbit isolated blood vessels. The rabbit isolated superior mesenteric artery, when precontracted with phenylephrine, relaxed in a sustained manner in less than 30 min following application of recombinant interleukin-1 beta (12-290 pM), and this was a prostaglandin (PG)-dependent and endothelium-independent process. IRA (human recombinant sequence; 0.9-15 nM) behaved as an antagonist of IL-1 alpha or IL-1 beta, based on the surmountability and the concentration dependence, but could only prevent the effect of IL-1, not reverse it. IRA had no direct effect on the preparation and did not influence the acute relaxing effect elicited by substance P or iloprost, a PGI2 mimetic. Exposure to IL-1 beta depressed the response to noradrenaline (NA) in several hours in rabbit aorta rings. The inhibitory effect of IL-1 beta was endothelium and prostaglandin independent, but was prevented by a treatment with NG-nitro-L-arginine (a nitric oxide synthesis inhibitor), cycloheximide, dexamethasone, or IRA. Using the residual NA-induced contraction as a quantification of the IL-1 agonist effect, IRA was a very potent antagonist of IL-1 beta but was not totally surmountable.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of interleukin-1 receptor antagonist on three types of responses to interleukin-1 in rabbit isolated blood vessels. 138 81

Body reaction to injury comprises two major pathways: the immune response, predominantly mediated by IL-1 and other cytokines, and neuroendocrine mechanisms, resulting in an increased glucocorticoid production. Each has distinct effects on prostaglandin (PG) production, which may in turn mediate both systemic and local inflammatory responses. The interactions, if any, between the two systems on PG synthesis have not been studied. Bovine aortic endothelial cell cultures were used and prostacyclin (PGI2) production was monitored. Cells were treated with dexamethasone (Dex) 10(-6) M and IL-1 10-30 U/ml in one experiment, and lipopolysaccharide (LPS, 0.1-1.0 micrograms/ml) in another experiment, separately or in combination, for either 2 or 24 + 2 h. While Dex was without effect, IL-1 and LPS stimulated PGI2 in a concentration- and time-dependent manner. Short exposure to Dex (2 h) enhanced the stimulation by IL-1 and LPS. On the contrary, more prolonged exposure (24 + 2 h) reversed the effects of IL-1 and LPS, resulting in PGI2 levels below the baseline. A biphasic regulation by Dex was also observed with increasing concentrations of LPS. Dex was actually ineffective by itself, but it enhanced PGI2 production in combination with lower concentrations of LPS, while abolishing the influence of higher concentrations of this agonist. The data suggest that Dex may initially stimulate phospholipase A2 (PLA2) activity, while inhibiting it later. This biphasic behavior may be attributed to different concentrations of a PLA2-modulating protein, possibly lipocortin, that accumulate during exposure to Dex.
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PMID:Biphasic regulation by dexamethasone of IL-1- and LPS-stimulated endothelial prostacyclin production. 141 91

This study demonstrates that bacterial lipopolysaccharide and lipid A exert a significant effect on eicosanoid formation by primary cultures of microvascular endothelial cells (MECs). Qualitative studies using [14C]-arachidonic acid demonstrated that prostaglandin E2 was the primary eicosanoid formed by MECs after 20 h of treatment with either vehicle or lipopolysaccharide. Significant, dose-dependent productions of PGE2 and prostacyclin, beginning at an endotoxin dose of 0.01 ng/ml, were quantified by radioimmunoassay in supernatants of cells treated for 20 h with lipopolysaccharide or lipid A. This eicosanoid production was inhibited by meclofenamate and cycloheximide and occurred without cellular injury. The time course and kinetics of eicosanoid production in response to endotoxin demonstrate a significant, time-related enhancement. Endotoxin-treated MECs responded to exogenous substrate with augmented PGE2 production, suggesting enhanced prostaglandin endoperoxide synthase activity. These results demonstrate a significant interaction of endotoxin with endothelial cells of microvascular origin that results in an enhanced potential for eicosanoid metabolism. This effect may be mediated in part through induction of prostaglandin endoperoxide synthase.
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PMID:Endotoxin enhances arachidonic acid metabolism by cultured rabbit microvascular endothelial cells. 141 70

Continuous lipopolysaccharide (LPS) infusion in pigs induced death in approximately half of the animals and a prolonged state of shock (up to 3 hours of experimental observation period, i.e., two hours after discontinuation of LPS infusion) in the surviving animals. Lethal-induced shock was marked by huge release of Tumor Necrosis Factor (TNF) into the blood, whereas eicosanoid and Platelet Activating Factor (PAF) levels remained unchanged. In pigs surviving LPS-infusion but still remaining in a state of shock, transient increases in PAF and thromboxane levels were observed, whereas prostacyclin and leukotrienes values remained above normal levels up to the end of the observation period. It is concluded that different types of mediators play a role in LPS-induced lethal shock as compared to non-lethal prolonged state of shock.
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PMID:Lethal and non-lethal course of endotoxic shock is determined by interactions between tumor necrosis factor, platelet activating factor and eicosanoids. 148 41

Arachidonic acid metabolism in normal rat incisor pulp was examined by measuring the conversion activity of exogenously added arachidonic acid in pulpal homogenates. It was demonstrated that the major metabolites were 12-hydroxyeicosatetraenoic acid and prostaglandin (PG) I2. Immunohistochemical studies revealed that PGI2 synthase was distributed in the pulpal blood-vessel cells, fibroblasts and odontoblasts, suggesting that PGI2 may contribute to regulating the function of these cells. When the incisor pulp was experimentally inflamed by applying lipopolysaccharide, arachidonic acid metabolism in the pulp showed overall increase. Change in the pulpal vascular permeability, which was assessed by quantifying the amount of extravasated dye, was almost parallel to the changes in PGE2 and PGI2 production. When production of the PGs was inhibited by indomethacin, the increase of vascular permeability in the inflamed pulp was also suppressed. Topically-applied PGE2 and PGI2 methyl ester abolished the suppression of increase in vascular permeability by indomethacin. These results suggest that PGE2 and PGI2 may be involved in the increase of vascular permeability in the experimental pulp inflammation. We further measured the production of leukotriene (LT) B4 in the inflamed pulp by incubating isolated pulp samples with Ca ionophore A23187, followed by radioimmunoassay. Change in LTB4 production was revealed to be almost parallel to that of neutrophil infiltration. BW755C, an inhibitor of both cyclooxygenase and lipoxygenase, reduced both LTB4 production and neutrophil infiltration. Accordingly, it was suggested that LTB4 may be involved in neutrophil infiltration in the experimental pulp inflammation.
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PMID:Pathophysiological roles of arachidonic acid metabolites in rat dental pulp. 150 2


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