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)

We have examined the effect of ONO-5046.Na, a synthetic specific inhibitor of neutrophil elastase, on lipopolysaccharide (LPS)-induced acute lung inflammation. Syrian golden hamsters were injected intraperitoneally with either 300 mg.kg-1 of ONO-5046.Na or saline, 30 min before and 1 h after intratracheal administration of 0.1 mg.kg-1 LPS. Animals were sacrificed 2 and 24 h later and the wet-to-dry lung weight ratio (W/D) was determined. Bronchoalveolar lavage (BAL) was performed, and tissue sections were examined histologically. The effect of ONO-5046.Na on migration of isolated neutrophils was determined. W/D was not significantly different at 2 h, but was increased at 24 h in the LPS-treated animals. This increase was attenuated in the LPS-treated animals injected with ONO-5046.Na. Analysis of BAL fluid revealed that both at 2 and 24 h after LPS administration the total cell number and neutrophil number, albumin concentration, and elastase-like activity were significantly lower in the LPS-treated animals injected with ONO-5046.Na than in those given LPS alone. Histological examination of the lungs of the animals treated with LPS alone showed intra-alveolar haemorrhages and inflammatory cell infiltration 24 h after LPS administration, whereas the lungs of the LPS-treated ONO-5046.Na injected animals were only sparsely infiltrated by inflammatory cells, as indicated by the inflammation score.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A specific neutrophil elastase inhibitor (ONO-5046.Na) attenuates LPS-induced acute lung inflammation in the hamster. 748 93

Angiotensinogen has been assumed to be an acute-phase protein, because some forms of acute inflammation, eg, the injection of lipopolysaccharide or cellite or partial hepatectomy, increased the hepatic synthesis of angiotensinogen. In addition, the well-characterized nephrectomy-induced stimulation of angiotensinogen was thought to represent an acute-phase reaction. To evaluate this hypothesis, we examined changes in angiotensinogen secretion by the isolated perfused rat liver after the systemic administration of turpentine or lipopolysaccharide as well as in response to nephrectomy or sham nephrectomy. Comparison was made with the secretion of two typical acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, and with the secretion of the negative acute-phase protein albumin. All forms of experimental surgery stimulated the secretion of both control acute-phase proteins several-fold. In contrast, the response of angiotensinogen was not uniform; lipopolysaccharide and bilateral nephrectomy stimulated secretion twofold to threefold, sham nephrectomy had no effect, and turpentine decreased the secretion to 30% of the control level. A similar inhomogeneity was found in an additional experiment performed to analyze the direct effects of interleukin-1 or interleukin-6 on the secretion of angiotensinogen by freshly isolated hepatocytes. Interleukin-6 increased but interleukin-1 decreased the mRNA and secretion of angiotensinogen, whereas both cytokines increased the secretion of both acute-phase proteins. Because of this nonuniform behavior of angiotensinogen, it is premature to classify angiotensinogen as an acute-phase protein until a specific function for angiotensinogen during acute inflammation is known.
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PMID:Angiotensinogen: an acute-phase protein? 750 96

1. The effect of endotoxin (E. coli lipopolysaccharide) on the induction of nitric oxide synthase (NOS) and the changes in vascular permeability in the colon and jejunum over a 5 h period have been investigated in the rat. 2. Under resting conditions, a calcium-dependent constitutive NOS, determined by the conversion of radiolabelled L-arginine to citrulline, was detected in homogenates of both colonic and jejunal tissue. 3. Administration of endotoxin (3 mg kg-1, i.v.) led, after a 2 h lag period, to the appearance of calcium-independent NOS activity in the colon and jejunum ex vivo, characteristic of the inducible NOS enzyme. 4. Administration of endotoxin led to an increase in colonic and jejunal vascular permeability after a lag period of 3 h, determined by the leakage of radiolabelled albumin. 5. Pretreatment with dexamethasone (1 mg kg-1 s.c., 2 h prior to challenge) inhibited both the induction of NOS and the vascular leakage induced by endotoxin. 6. Administration of the NO synthase inhibitor NG-monomethyl-L-arginine (12.5-50 mg kg-1, s.c.) 3 h after endotoxin injection, dose-dependently reduced the subsequent increase in vascular permeability in jejunum and colon, an effect reversed by L-arginine (300 mg kg-1, s.c.). 7. These findings suggest that induction of NOS is associated with the vascular injury induced by endotoxin in the rat colon and jejunum.
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PMID:The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. 750 78

To clarify the mechanism involved in regulating the secretion of albumin and alpha 1-acid glycoprotein by rat hepatocytes, we studied hepatocyte culture and cocultures of hepatocyte and liver nonparenchymal cells. The secretion of alpha 1-acid glycoprotein by hepatocytes was stimulated and that of albumin was inhibited by combinations of dexamethasone and monokines, especially by dexamethasone and interleukin-6. The secretion of these proteins was equally inhibited during stimulation by lipopolysaccharide in cocultures. The inhibitory effect of sinusoidal endothelial cells was smaller than that of Kupffer cells. This inhibition was partially abolished by blocking the nitric oxide synthase pathway in cocultured cells and was completely abolished by dexamethasone. In conclusion, the secretion of albumin and alpha 1-acid glycoprotein by hepatocytes was regulated by monokines, dexamethasone, and the inducible nitric oxide synthase pathway in hepatocytes and liver nonparenchymal cells in vitro.
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PMID:Regulation of hepatocyte albumin and alpha 1-acid glycoprotein secretion by monokines, dexamethasone, and nitric oxide synthase pathway: significance of activated liver nonparenchymal cells. 751 18

1. The effects of the nitric oxide (NO) synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the vascular damage induced by the endotoxin, E. coli lipopolysaccharide (LPS), in the ileum and colon were investigated in the conscious rat over a 5 h period. 2. Administration of LPS (3 mg kg-1, i.v.) increased ileal and colonic vascular injury after a lag period of 2 h, as determined by the leakage of radiolabelled albumin. 3. Administration of L-NAME (1-5 mg kg-1, s.c.) concurrently with LPS, produced a dose-dependent increase in vascular albumin leakage in the intestinal tissues, when determined over a 5 h period. Vascular albumin leakage with LPS and L-NAME (5 mg kg-1) was substantially increased after 1 h, reached maximal levels 3 h after administration, and then slowly declined. 4. L-NMMA (50 mg kg-1, s.c.), likewise elevated intestinal albumin leakage when administered concurrently with LPS, but this reached maximal levels after 1 h and rapidly declined over the subsequent 2 h. 5. In control rats, in the absence of LPS challenge, neither L-NAME (5 mg kg-1, s.c.) nor L-NMMA (50 mg kg-1, s.c.) increased intestinal vascular leakage of albumin over a 5 h period. 6. By contrast, when L-NAME (1-5 mg kg-1, s.c.) or L-NMMA (12.5-50 mg kg-1, s.c.) was injected 3 h after LPS, a dose-dependent reduction in the LPS-provoked vascular albumin leakage was observed. 7 Pretreatment with L-arginine (300 mg kg-1, s.c.) 15 min prior to the NO synthase inhibitors, reversed either the potentiation or the inhibition by L-NAME (5 mg kg-1, s.c.) or L-NMMA (50 mg kg-1, s.c.) of the LPS-induced intestinal vascular damage.8. These findings indicate that initial suppression of the constitutive NO synthase by L-NAME orL-NMMA following challenge with LPS aggravates the acute vascular injury in the ileum and colon,suggesting a defensive role of NO. By contrast, the delayed administration of NO synthase inhibitors, ata time of known expression of the inducible NO synthase, provides protection against the subsequent damage to the intestinal vasculature.
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PMID:Time-dependent enhancement or inhibition of endotoxin-induced vascular injury in rat intestine by nitric oxide synthase inhibitors. 751 98

A comparative study of leukocyte adhesion to the endothelium of the thoracic aorta and left carotid artery in rats has been performed after administration of two hyperlipidemic diets for 15 days, proinflammatory agents (thrombin, lipopolysaccharide and zymosan activated serum) and plasma expanders [dextran, polyvinylpyrrolidone (PVP), rat albumin and several bovine albumins from different sources]. Leukocytes adhered to the endothelium were demonstrated in surface preparations by esterase activity. Activation of circulating leukocytes was measured by nitroblue tetrazolium reduction and luminol enhanced chemiluminescence. Both hyperlipidemic diets produced, in all rats, more leukocyte adhesion in the aorta than in the carotid artery. All proinflammatory agents produced at 1 h, increases in leukocyte adhesion--which in all rats were greater in the carotid artery than in the aorta--and leukocyte activation, which was higher at 3 h than at 1 h. Dextran, PVP, bovine albumins 103700 and A-4503 at 18 h produced slight increases in leukocyte adhesion in the aorta but not in the carotid artery. Rat albumin and bovine albumin A-7906 determined an intense leukocyte adhesion at 18 h which was not preferential to either vessel. Adhesion produced by A-7906 was maximal at 12 h and partially inhibited by dexamethasone. This last albumin produced leukocyte activation at 3 h and was sequestered 5 min after administration, reaching normal values at 1 h. Albumins 103700 and A-4503 neither activated leukocytes nor were sequestered after administration.
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PMID:Effect of hyperlipidemic diets, proinflammatory agents and plasma expanders on leukocyte adhesion to the endothelium of aorta and carotid artery of rats. 753 42

The effects of aminoguanine on the intestinal vascular permeability following endotoxin administration in vivo has been compared to those of the nitric oxide (NO) synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) in the rat. Concurrent administration of aminoguanidine. (12.5-50 mg/kg, s.c.) with endotoxin (E. coli lipopolysaccharide, 3 mg/kg, i.v.), dose dependently increased vascular leakage of radiolabelled albumin in the ileum and colon after 1 h, an effect reversed by the pretreatment with L-arginine (300 mg/kg, s.c.). Aminoguanidine (50 mg/kg, s.c.) also elevated arterial blood pressure over the 1 h investigation period. Similar acute potentiation of endotoxin-provoked vascular injury was observed 1 h following L-NMMA (50 mg/kg s.c.) which also increased blood pressure, indicating the inhibition of constitutive NO synthase. By contrast, administration of aminoguanidine (12.5-50 mg/kg, s.c.) 3 h after endotoxin, at the time of the expression of the inducible NO synthase, reduced the subsequent endotoxin-induced vascular leakage, as did L-NMMA (50 mg/kg). In homogenates of rat ileal or colonic tissue, aminoguanidine inhibited both the constitutive and inducible NO synthase activity showing only 2-fold selectivity for the inducible isoform. Thus, although aminoguanidine inhibits these isoforms of NO synthase, it is not a selective inhibitor of the inducible isoform in the intestinal microvasculature in vivo.
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PMID:Aminoguanidine inhibits both constitutive and inducible nitric oxide synthase isoforms in rat intestinal microvasculature in vivo. 753 62

The regulation of acute-phase protein production and nitric oxide (NO) release in lipopolysaccharide-induced liver injury is thought to occur in response to monocytes/macrophages and Kupffer-cell-derived cytokines. In this study, we used primary cultured rat hepatocytes maintained as a differentiated phenotype to investigate the direct effects of endotoxin (lipopolysaccharide) on the production of the acute-phase proteins and on NO release. Lipopolysaccharide (10 micrograms/ml) increased the production of alpha 2-macroglobulin 2.5-fold compared to untreated cultures and decreased the production of albumin by 50%. The effect of lipopolysaccharide was mimicked by adding interleukin-6 (IL-6) and tumor-necrosis factor alpha (TNF-alpha), cytokines being induced by treatment of hepatocytes with lipopolysaccharide. Maximal TNF-alpha (600 pg/ml) and IL-6 (1800 pg/ml) concentrations were observed 4 h and 6 h after lipopolysaccharide stimulation, respectively. The lipopolysaccharide-induced acute-phase protein response was blocked by anti-(IL-6) but not by anti-(TNF-alpha) IgG. The latter reduced the lipopolysaccharide-induced IL-6 production by 60%. Besides its effects on the acute-phase proteins, endotoxin caused a significant increase in NO production in cultured rat hepatocytes. Unlike anti-(IL-6) IgG, anti-(TNF-alpha) IgG reduced the lipopolysaccharide-induced NO production by 50% indicating that endotoxin-induced NO production is partially mediated by TNF-alpha but not by IL-6. Preculture with gadolinium chloride (GdCl3), an inhibitor of Kupffer cells, did not change the response of hepatocytes to lipopolysaccharide indicating that the observed findings are direct endotoxin effects on hepatocytes. The data demonstrate that by their production of TNF-alpha and IL-6 rat hepatocytes respond to lipopolysaccharide treatment with an IL-6 mediated acute-phase protein and a TNF-alpha-mediated NO production. These features have previously been attributed to monocytes/macrophages and Kupffer cells.
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PMID:Hepatocyte-derived interleukin-6 and tumor-necrosis factor alpha mediate the lipopolysaccharide-induced acute-phase response and nitric oxide release by cultured rat hepatocytes. 753 77

The effect of dietary protein concentration on stress responses against injection of Escherichia coli lipopolysaccharide (LPS) was studied in male broiler chickens. Chickens (7 d of age) were fed on a 100 (low-protein; LP) or 300 g protein/kg (high-protein; HP) diet for 2 weeks. LPS was injected intraperitoneally every 2 d during the final 6 d, or once 16 h before the end of the experiment, at a concentration of 900 micrograms/chick. The LPS injection did not affect body-weight gain, feed intake, gain:intake ratio, or plasma Fe concentration. The single injection of LPS reduced plasma Zn concentration, but the repeated injections did not. Feeding the HP diet increased the response of plasma Zn concentration to the single injection of LPS. Plasma albumin concentration was reduced by LPS injection. Feeding the HP diet resulted in a higher plasma alpha 1-acid glycoprotein (AGP) concentration than feeding the LP diet, in chicks untreated with LPS. An increase in plasma AGP concentration observed after LPS injection in chicks fed on the LP diet was greater than that seen in chicks fed on the HP diet. No significant changes in plasma AGP concentration in response to repeated injections of LPS were observed in chicks fed on the HP diet. Plasma interleukin-1 (IL-1)-like activity was greater in chicks fed on the LP diet than in those fed on the HP diet, when LPS was injected. The response of plasma IL-1-like activity to the single injection of LPS in chicks fed on the LP diet was the greatest among the treatment groups. These results suggest that acute-phase responses to LPS injection are much greater in chicks fed on a LP diet than in those fed on a HP diet, and multiple injection of LPS weakens the responses.
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PMID:Effect of dietary protein concentration on responses to Escherichia coli endotoxin in broiler chickens. 754 35

1. The effects of the nitric oxide (NO) donors, S-nitroso-glutathione (SNOG) and S-nitroso-N-acetyl-penicillamine (SNAP), on the acute intestinal microvascular dysfunction induced by NG-nitro-L-arginine methyl ester (L-NAME) in combination with low doses of endotoxin were investigated in the anaesthetized rat. 2. Administration of L-NAME (5 mg kg-1, s.c.) concurrently with E. coli lipopolysaccharide (LPS, 3 mg kg-1, i.v.) provoked the leakage of radiolabelled albumin in the ileum and colon, as a measure of microvascular damage, determined 1 h after challenge. 3. Intravenous infusion of SNOG or SNAP (1-10 micrograms kg-1 min-1) dose-dependently attenuated the microvascular leakage induced by L-NAME and LPS. 4. Infusion of the lowest doses of SNOG or SNAP (1 microgram kg-1 min-1, i.v.) that significantly reduced the albumin leakage, did not affect the increase in blood pressure in response to L-NAME in LPS-treated rats. Higher doses of SNOG or SNAP (5-10 micrograms kg-1 min-1, i.v.) dose-dependently reduced this increase in blood pressure. 5. In control studies, intravenous infusion of glutathione (10 micrograms kg-1 min-1) or N-acetyl-penicillamine (10 micrograms kg-1 min-1) had no effect on microvascular leakage in the ileum and colon induced by LPS and L-NAME. 6. Pretreatment with rabbit anti-rat neutrophil serum (0.4 ml kg-1, i.p., 4 h before challenge), which reduced the neutrophil count in peripheral arterial blood, also inhibited the microvascular leakage in the ileum and colon. 7. The protective effects of the nitrosothiol NO donors in this model may reflect, in part, modulation of neutrophil interactions within the microcirculation or actions on endothelial cell integrity, in addition to any local vasodilator action.
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PMID:Attenuation by nitrosothiol NO donors of acute intestinal microvascular dysfunction in the rat. 758 63


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