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)

To investigate the role of polymorphonuclear leukocytes in galactosamine-induced hepatic injury, we injected rats intraperitoneally with antiserum against rat polymorphonuclear leukocytes to deplete circulating neutrophils, then administered galactosamine plus lipopolysaccharide. Polymorphonuclear leukocytes in the hepatic sinusoids were increased after administration of galactosamine plus lipopolysaccharide, whereas pretreatment with the antiserum decreased the number of circulating leukocytes and reduced the mortality and the severity of hepatic injury. Serum collected 1 hr after galactosamine/lipopolysaccharide treatment enhanced in vitro polymorphonuclear leukocyte adherence to hepatic endothelial cells and induced leukocyte superoxide production. Intercellular adhesion molecule-1 expression on hepatic endothelial cells was also enhanced after stimulation with the serum. Polymorphonuclear leukocyte adhesion was partially inhibited by an antibody against tumor necrosis factor-alpha but not by superoxide dismutase. These results suggest that polymorphonuclear leukocytes play an important role in galactosamine-induced hepatic injury and that the accumulation and activation of leukocytes, as well as the enhanced expression of adhesion molecules on hepatic endothelial cells, can be induced by biologically active mediators such as tumor necrosis factor-alpha. In addition, prostaglandins E1 and E2 lessened the enhanced adherence of polymorphonuclear leukocytes and thus contributed to protection against hepatic injury.
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PMID:Role of polymorphonuclear leukocytes in galactosamine hepatitis: mechanism of adherence to hepatic endothelial cells. 798 55

The effects of methylprednisolone succinate (MP) on plasma lipid peroxidation, plasma SOD activity and superoxide production in polymorphonuclear leukocytes (PMNs) induced by lipopolysaccharide (LPS) were examined in rats in vivo and in vitro. In rats subjected to LPS treatment, plasma phosphatidylcholine hydroperoxide (PCOOH) levels significantly increased, and the plasma Cu,Zn-SOD activity decreased by about 75%. When rats were given 30 mg/kg of MP intravenously, MP suppressed the elevation of plasma PCOOH levels and partially inhibited the decrease in plasma Cu,Zn-SOD activity. MP also suppressed PMA-induced superoxide production in PMNs primed by LPS. In in vitro experiments, low concentrations of MP had no effect on NADPH-dependent lipid peroxidation, but 4 mM MP produced 50% inhibition. MP had little effect on PMA-induced superoxide production in PMNs primed by LPS. Moreover, MP had no radical-trapping effect on superoxide, hydroxyl radical and stable DPPH radical. These results suggest that the suppressive effect of plasma lipid peroxidation by MP is not due to radical-trapping effects or preventive anti-oxidation, but may involve the suppression of the lipid chain reaction in liver membrane resulting from PMA-induced superoxide anions generated by PMNs.
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PMID:Effect of methylprednisolone on plasma lipid peroxidation induced by lipopolysaccharide. 802 18

To determine whether cytokines or lipopolysaccharide (LPS) are involved in the induction of superoxide dismutase (SOD) in the nervous system, we examined the effects of these substances on the levels of SOD in cultured mouse astrocytes. Treatment of astrocytes with 10(2) to 10(4) U/ml tumor necrosis factor-alpha for 3 days increased the levels of Mn SOD in a dose- and time-dependent manner to as much as six times the level under nontreated conditions. Treatment with 1.0 microgram/ml LPS for 3 days elicited a fourfold increase in levels of Mn SOD, and the effect of LPS was also dose dependent. Furthermore, Mn SOD in astrocytes was induced by a 3-day exposure to interleukin-1 alpha at concentrations of 10(2) or 10(3) U/ml. However, these stimuli had no effect on levels of copper-zinc SOD (Cu/Zn SOD) in astrocytes. By contrast, interferon-gamma did not change the levels of either Mn or Cu/Zn SOD in the cells. The results indicate that the selective induction of Mn SOD by cytokines and LPS, which has been observed in nonnervous tissues, may also occur in nervous tissues. The induction of Mn SOD may represent a mechanism for protection of cells from oxidative stress.
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PMID:Induction of manganese superoxide dismutase by cytokines and lipopolysaccharide in cultured mouse astrocytes. 803 84

Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-kappa B protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-kappa B activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-kappa B protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-kappa B subunits were detected on gel supershift assays. Minimal NF-kappa B activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-kappa B activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-kappa B activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models.
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PMID:Dimethyl sulfoxide modulates NF-kappa B and cytokine activation in lipopolysaccharide-treated murine macrophages. 803 80

Parenteral injection of the cytokines interleukin-1 and tumor necrosis factor, or of endotoxin (lipopolysaccharide), protects rats against lethal pulmonary oxygen toxicity. To determine the potential importance of manganese superoxide dismutase (MnSOD) in this model, we measured MnSOD mRNA and activity in lung. In addition, we confirmed that increases in activities were related to changes in MnSOD protein, which was measured using an enzyme-linked immunosorbentassay (ELISA) technique. After cytokine or endotoxin administration, increases in lung MnSOD mRNA occurred promptly (4 h), with or without hyperoxic exposure. In parallel, lung MnSOD protein and activity were increased after 24 h, and protein levels remained elevated after 52 h. MnSOD activity and protein levels were closely correlated. Neither lung copper-zinc superoxide dismutase (CuZnSOD) mRNA nor activity increased following administration of cytokines. Small increases in CuZnSOD mRNA, which did not exceed those in beta-actin mRNA, occurred early (4 h) after endotoxin, but CuZnSOD activity was unchanged. Immunohistochemistry was used to demonstrate in which cell types the increase in MnSOD protein occurred after cytokine or endotoxin administration. In agreement with ELISA findings, immunoreactive MnSOD appeared to be increased in lung parenchyma, but not in lung neutrophils, 24 h after cytokine or endotoxin treatment. MnSOD was heavily concentrated in alveolar type II cells. However, the numbers of surfactant protein D-positive (type II) cells in lung sections did not appear to be increased after treatment with cytokines or endotoxin. We conclude that early and sustained increases in endogenous MnSOD, but not CuZnSOD or other antioxidant enzymes, are associated with protection of rat lungs against hyperoxic damage by cytokines or endotoxin.
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PMID:Lung manganese superoxide dismutase increases during cytokine-mediated protection against pulmonary oxygen toxicity in rats. 811 Apr 68

Murine macrophages can be activated to produce nitric oxide (NO) and superoxide and these two radicals can react to form peroxynitrite, a powerful oxidant which may be involved in parasite killing. We now show that murine macrophages activated with zymosan and interferon-gamma (ZYM/IFN-gamma) produced both superoxide (peaking 1-2 h after stimulation, then rapidly declining) and NO (barely detectable at 6 h, peaking by 24 h). Macrophages activated with ZYM alone produced only superoxide, while stimulation with lipopolysaccharide (LPS) and IFN-gamma induced NO but not superoxide. Cells stimulated with ZYM/IFN-gamma or LPS/IFN-gamma killed Leishmania major to a similar degree, an effect that was completely blocked by the addition of N-iminoethyl-L-ornithine. However, macrophages stimulated with ZYM alone were unable to kill L. major. S-nitroso-acetyl-penicillamine, which releases NO, was highly leishmanicidal when added directly to the parasites. 3-morpholino-sydnonimine hydrochloride which releases both NO and superoxide simultaneously, was also efficient at killing L. major and this cytotoxicity was greatly enhanced by the addition of superoxide dismutase. Finally, authentic peroxynitrite failed to induce any cytotoxic effect, even at a high concentration. Thus macrophages can produce either NO, superoxide or both, depending on the stimulus. However, the killing of L. major is dependent only on the production of NO.
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PMID:Production of nitric oxide and superoxide by activated macrophages and killing of Leishmania major. 812 36

SC-45662 and SC-41661A, selective arachidonate 5-lipoxygenase (5-LO) inhibitors, had markedly different effects on formyl-methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a (C5a) induced superoxide release from human neutrophils (PMNs). SC-45662 inhibited superoxide generation induced by fMLP and C5a with IC50 values of 12 and 5 microM, respectively. Furthermore, SC-45662 was capable of inhibiting fMLP and C5a induced superoxide release in PMNs primed with bacterial lipopolysaccharide, tumor necrosis factor-alpha and other priming agents. SC-41661A, a compound from the same chemical series as SC-45662, did not inhibit or induce superoxide generation, but instead primed PMNs for fMLP and C5a induced superoxide generation. The induced superoxide release was concentration dependently enhanced 2 to 4-fold at 5-50 microM. Superoxide release induced by phorbol myristate acetate or serum-activated zymosan was unaffected by either SC-45662 or SC-41661A. The regulation of superoxide generation by these compounds, both of which have the identical oxidation-reduction pharmacophore, was clearly independent of their effects on 5-LO activity. Furthermore, the mechanism by which SC-45662 and SC-41661A alter superoxide generation did not appear to depend on inhibition of xanthine oxidase, catalase or superoxide dismutase. These new compounds provide effective tools for further investigation of the relationship of these two biochemical oxidative systems.
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PMID:Contrasting effects of two arachidonate 5-lipoxygenase inhibitors on formyl-methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a induced human neutrophil superoxide generation. 814 1

Intravenous administration of bacterial endotoxin (lipopolysaccharide: LPS) induces shock and disseminated intravascular coagulation in rats. Our report here shows that LPS-administered rats (10 mg/100 g) develop tissue injuries and functional disorders in multiple vital organs. In the present study, we investigated changes in tissue antioxidant enzyme activities, neutrophil sequestration, and lipid peroxides in multiple organs (lung, stomach, small intestine for antioxidant enzyme activities and neutrophil sequestration; lung, stomach, small intestine, liver, abdominal aorta for lipid peroxides) of LPS-treated rats. LPS-treated animals morphologically revealed pulmonary interstitial edema, alveolar hemorrhage, and mucosal hemorrhage in the small intestine 45 min after LPS administration. Blood samples withdrawn from LPS-treated animals exhibited increases in serum amylase, blood urea nitrogen, creatinine, and transaminase levels up to 180 min post-LPS infusion. LPS-treated animals showed a significant increase in tissue myeloperoxidase (MPO) activities of the lung, but not of the small intestine and stomach 45 min after LPS infusion. Thiobarbituric acid reactive substances (TBARS) in the lung, small intestine, stomach, liver, and abdominal aorta significantly increased at 45 min post-LPS-infusion. Tissue superoxide dismutase (SOD) activities of the LPS-treated animals demonstrated a significant decrease in the lung, which suffered from severe insults and neutrophil sequestration; no significant change in the small intestine, which suffered from morphological insults without neutrophil sequestration, and a significant increase in the stomach, which showed no histological impairment, at 180 min post-LPS administration. Glutathione peroxidase (GSH-PX) activities of the lung and small intestine showed no significant change in LPS-treated rats, while those of the stomach revealed a marked increase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in tissue antioxidant enzyme activities and lipid peroxides in endotoxin-induced multiple organ failure. 814 10

1. We describe a rapid and reliable technique for the assessment of basal nitric oxide release in clinical situations, using peripheral blood polymorphonuclear leucocytes isolated by a single-step density gradient procedure. The assay is based on the quantitative conversion of oxyhaemoglobin to methaemoglobin by nitric oxide. We have further examined the ability of these cells to respond to various stimuli. 2. Basal (unstimulated) nitric oxide release occurred, which was augmented by superoxide dismutase. The mean value for healthy subjects was 283 +/- 96.7 pmol min-1 10(-6) cells. 3. Both phorbol myristate acetate and N-formyl-methionyl-leucylphenylalanine induced further release of nitric oxide, which was increased by preincubation with lipopolysaccharide, interleukin-6 and interferon-gamma. 4. Preincubation of cells with NG-monomethyl-L-arginine or L-canavanine sulphate inhibited nitric oxide production. 5. The procedure provides a valuable tool for monitoring nitric oxide up-regulation in clinical situations.
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PMID:Nitric oxide production by human peripheral blood polymorphonuclear leucocytes. 816 35

The antiinflammatory efficacy of CuPu(Py)2 ([[N,N'-bis(2-pyridylmethylene)-1,4-butanediamine] (N,N',N'',N''')]-Cu2+), a serum stable active center analog of Cu2Zn2superoxide dismutase (SOD), was tested in vitro and in vivo in male Wistar rats suffering from potassium peroxochromate-induced inflammation. Parameters including 99mTc gamma-scintigraphic imaging, the arthritis score, the plasma superoxide dismutase activity, the inhibition of plasma sulfhydryl depletion as well as mitogenic and phagocytic responses were used to quantify the disease activity. All parameters improved impressively during the treatment with CuPu(Py)2 and resembled those of healthy animals after 21 days. The arthritis score was inhibited by 80% (P > 0.001) and the plasma SOD activity enhanced by 380% (P > 0.001). The depletion of plasma sulfhydryls and the leukocytic responses to concanavalin A, tetradecanoylphorbolacetate, and lipopolysaccharide were significantly reduced (P > 0.001) and correlated well with the arthritis score. The collapse of antioxidant defenses in human plasma as well as the depolymerization of hyaluronic acid was mimicked in vitro and successfully inhibited by CuPu(Py)2. Oxidant-induced injury of plasma components during the aqueous decay of potassium peroxochromate were demonstrated to activate the oxidative burst of phagocytes in human blood. The role of impaired pro- and antioxidant balances in the etiology of inflammatory and autoimmune rheumatic diseases is discussed.
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PMID:Reactivity of an active center analog of Cu2Zn2superoxide dismutase in murine model of acute and chronic inflammation. 822 66


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