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 investigated the role of interleukin 1 alpha (IL 1 alpha) in the pathogenesis of chronic liver disease. IL 1 alpha production by peripheral blood monocytes was measured with a specific, sensitive double-antibody radioimmunoassay. When monocytes were cultured for two days with bacterial lipopolysaccharide (LPS), IL 1 alpha production in asymptomatic hepatitis B virus carrier (ASC) and patients with chronic active hepatitis (CAH) was equivalent to that of controls (168 +/- 31 U/ml, mena +/- SD), while IL 1 alpha levels generated by monocytes from liver cirrhosis (LC) (117 +/- 45 U/ml, p less than 0.01) were significantly lower than controls. When normal monocytes were cultured together with LPS and IFN gamma, mena IL 1 alpha production was 297 +/- 56 U/ml. IL 1 alpha production in ASC did not differ from controls. On the other hand, IL 1 alpha production in patients with CAH (241 +/- 58 U/ml, p less than 0.05) and LC (189 +/- 70 U/ml, p less than 0.01) were significantly diminished in comparison with controls although there was considerable overlap. Serial study demonstrated that IL 1 alpha production rose significantly during acute deterioration of illness with marked rise in serum alanine aminotransferase. The addition of sera to normal monocytes cultures resulted in significantly enhanced suppression (p less than 0.05) for IL 1 alpha production in comparison with that of control sera. These findings indicate that decreased monocyte function and serum inhibitor(s) for IL 1 alpha production could contribute to the pathogenesis of chronic liver disease.
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PMID:Interleukin 1 alpha production by peripheral blood monocytes from patients with chronic liver disease and effect of sera on interleukin 1 alpha production. 314 31

Tumor necrosis factor (TNF) has been shown to mediate lipopolysaccharide-induced neutrophil adhesion to liver sinusoidal endothelium in vivo. Female NMRI mice received either 5 micrograms lipopolysaccharide (R595) per animal alone (model A) or together with 116 mumol D-galactosamine (model B). One hour after injection, TNF activity in the serum was detectable to an equal extent in both models. Neutrophils in the liver, which had been identified by chloroacetate esterase staining of liver sections and quantitated by light microscopy, started to increase at 1 h and were elevated 10-fold above baseline at 6 h after application in (A) and (B). If 0.5 micrograms TNF instead of lipopolysaccharide was injected alone (model C) or together with D-galactosamine (model D), neutrophil influx into the liver was comparable to that observed in (A) or (B). Alanine aminotransferase activity in the serum was nearly normal in (A) and (C) 6 h after injection, while it reached levels up to 50-fold above baseline in models (B) and (D). This reflects the well-known D-galactosamine sensitization against lipopolysaccharide or TNF. Furthermore, degranulation of a large number of intrasinusoidal neutrophils could be observed 9 h after lipopolysaccharide-galactosamine injection. The administration of 116 mumol D-galactosamine per animal alone led neither to a measurable TNF activity in the serum nor to an increase in alanine aminotransferase activity or number of liver neutrophils. If the animals had received 50 microliter turpentine subcutaneously 24 h prior to lipopolysaccharide, TNF or D-galactosamine injection, the induced acute-phase reaction suppressed the increase of liver neutrophils in all models. Acute-phase reaction also prevented neutrophil degranulation and the rise of alanine aminotransferase in (B) to a great extent, while serum TNF activity was only minimally affected. It is concluded that TNF mediates neutrophil adhesion to the sinusoidal endothelium in vivo and that acute-phase reactants prevent lipopolysaccharide- or TNF-induced neutrophil influx into the liver.
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PMID:Involvement of tumor necrosis factor in endotoxin-triggered neutrophil adherence to sinusoidal endothelial cells of mouse liver and its modulation in acute phase. 319 26

Experimental liver injury was produced in mice by the immunological technique. The utility of these models as an immunopharmacological method was investigated. The first model was produced by the injection of anti-basic liver protein (BLP) rabbit antibody into DBA/2 mice that had been previously immunized with rabbit IgG. The second liver injury was caused by injection of anti-liver specific protein (LSP) rabbit antibody into DBA/2 mice. The third model was produced by the injection of bacterial lipopolysaccharide (LPS) into Corynebacterium parvum pretreated ddY mice. In all injury models, extensive liver parenchymal cell damage was estimated by elevation of glutamate transaminase (GOT and GPT) activity. These were confirmed by histopathological studies of the liver. Typical histopathological changes in the liver from injured mice were submassive hepatocellular necrosis and infiltration of granulocytes and lymphocytes into the portal tract and sinusoid in the necrotic lesion. Administration of prednisolone and cyclophosphamide for 10 days prior to injection of eliciting antibodies or LPS suppressed the elevation of serum transaminase levels in all experimental liver injury models. Cianidanol and sylibin inhibited the elevation of GOT and GPT in anti-BLP induced liver injured mice. These evidences suggest that the above models are suitable for investigating the remedy for liver diseases.
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PMID:Liver injury model in mice for immunopharmacological study. 337 35

Two strains of mice (C57BL/10ScN and C3H/HeJ) that carry the same mutant lipopolysaccharide gene (Lpsd) which makes them resistant to the toxic effects of endotoxin (LPS) are also partially resistant to the hepatotoxic effects of D-galactosamine. As measured by serum alanine aminotransferase, the degree of liver injury induced by D-galactosamine in the LPS-resistant strains is only 10%-30% that of closely related strains of LPS-sensitive mice. Similarly, histopathologic changes are less pronounced in the endotoxin-resistant strains than in LPS-susceptible mice. By transferring spleen cells from LPS-susceptible strains to lethally irradiated, LPS-resistant mice, we established that susceptibility to D-galactosamine is mediated by lymphoreticular cells. Radiation-resistant spleen cells transferred D-galactosamine sensitivity, suggesting a role for macrophages. We did not exclude the possibility that lymphocytes can also transfer the response to D-galactosamine. These results establish that in mice, D-galactosamine sensitivity is associated with endotoxin sensitivity and that the former is mediated by lymphoreticular cells, not by hepatocytes.
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PMID:D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. 388 May 54

The aim of our study was to determine the role of cytokine interleukin-1-beta (IL-1-beta) in patients with chronic hepatitis C virus (HCV) infection. Twenty-eight patients with chronic HCV infection were studied and compared with 18 healthy subjects. IL-1-beta levels were measured with an enzyme-linked immunosorbent assay in plasma and in supernatants of peripheral blood mononuclear cells (PBMC) incubated alone or in the presence of lipopolysaccharide (LPS). No IL-1-beta was found in plasma or unstimulated PBMC supernatants. The mean LPS-induced IL-1-beta production was 20.0 +/- 4.0 ng/ml in patients with chronic HCV infection and 29.4 +/- 3.7 ng/ml in the control group. The patients had significantly lower levels of LPS-induced IL-1-beta than the control group (p < 0.00001). No difference in LPS-induced IL-1-beta production was found in patients in relation to the histologic diagnosis (p > 0.05). There was no correlation between LPS-induced IL-1-beta production and serum alanine aminotransferase levels in patients with chronic HCV infection (r = 0.37, p > 0.05). Although limited to a small number of cases, our results suggest that LPS-induced IL-1-beta production by PBMC is impaired in patients with chronic HCV infection.
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PMID:Impaired lipopolysaccharide-induced interleukin-1-beta production in patients with anti-hepatitis C virus antibody-positive chronic liver disease. 751 90

This study examines the effect of chronic alcohol consumption on nitric oxide release from the liver of rats with or without lipopolysaccharide (LPS) (Escherichia coli) treatment. Reactive nitrogen intermediates (RNIs) in plasma were monitored with an NOx Analyzer, and nitric oxide (NO) production was measured as nitrite or nitrite + nitrate accumulation in perfusates of the perfused liver, and in supernatants of the freshly isolated hepatic cells after incubation for 3 hr in Hank's balanced salt solution buffer containing 1 mM L-arginine. RNI concentration in plasma of control rats was 32.0 +/- 3.4 microM (mean +/- SE). Livers from diet-fed control rats produced RNIs at the barely detectable rate of 7.8 +/- 1.5 nmol/hr x g wet liver. Six hr after administration of LPS (1 mg/kg, i.v.), plasma RNI levels in diet-fed control rats increased to 426.9 +/- 29.4 microM, and RNI release from the perfused liver was also markedly elevated to 97.7 +/- 7.7 nmol/hr x wet g liver, indicating hepatic NO release as a potentially important source for the increased RNI in plasma. The presence of NG-monomethyl-L-arginine (0.5-1 mM) or the absence of L-arginine in the perfusate inhibited LPS-induced stimulation of RNI release. EGTA (1 mM) had little effect, indicating that the increased RNI release was likely to be due to inducible NO synthase activity. The release of RNIs by freshly isolated Kupffer cells increased 13-fold, and this small cell mass contributed almost half of the hepatic RNI production under these conditions. Plasma ALT concentration was elevated after LPS administration, indicating incipient liver damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic alcohol administration stimulates nitric oxide formation in the rat liver with or without pretreatment by lipopolysaccharide. 754 48

Hepatocyte growth factor (HGF), a potent hepatocyte mitogen in vitro, triggers hepatocyte regeneration after partial hepatectomy and acute liver cell necrosis induced by chemicals. In contrast, transforming growth factor beta 1 inhibits hepatocyte proliferation in vitro and suppresses liver regeneration in vivo. We assessed the expression of HGF and TGF beta 1 mRNA in an endotoxin-related hepatic cell necrosis model. Intravenous injection of Gram-negative lipopolysaccharide (LPS) into rats previously given heat-killed Propionibacterium acnes induced endotoxin-related hepatic cell necrosis. In this model, serum ALT began to rise to more than 100IU as early as 3 h after LPS injection, reaching 300IU 12h after injection. HGF mRNA levels in the liver did not increase significantly until 5h after LPS injection; at 12h, they had increased about threefold compared with controls. TGF beta 1 mRNA expression increased threefold after P. acnes treatment alone and increased further after LPS injection. In the spleen, HGF mRNA levels increased within 3h, but in the lung no increase in HGF mRNA was observed. Early elevation of liver TGF beta 1 mRNA levels and delayed elevation of HGF mRNA levels, with low expression of HGF in the lung, may play a role in the pathogenesis of endotoxin-related hepatic necrosis.
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PMID:Expression of hepatocyte growth factor and transforming growth factor beta 1 mRNA in P. acnes and lipopolysaccharide-treated rats. 771 14

Liver injury is common in patients following hemorrhage and sepsis. There are multiple etiologies for this liver injury which involve both decreased nutrient blood flow and direct cellular injury. Enteral nutrients vasodilate gut blood vessels and increase blood flow to the intestines and liver. Since enteral nutrients vasodilate gut blood vessels, we wondered whether luminal nutrition would prevent hepatic injury during shock states. We randomized Sprague-Dawley rats to saline or enteral nutrition via duodenal feeding tubes. Animals were then subjected to 60 min of hemorrhagic hypotension or intraperitoneal injection of lipopolysaccharide (LPS). Liver injury was assessed by measuring levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) before and after hemorrhage or LPS. Enteral nutrients significantly decreased liver injury following hemorrhage. AST increased from 246 +/- 17 to 1605 +/- 593 U/L in saline animals and 283 +/- 39 to 551 +/- 94 U/L in enterally fed animals. ALT increased from 60 +/- 4 to 726 +/- 355 U/L in saline animals and 61 +/- 6 to 161 +/- 38 U/L in enterally fed animals. Enteral nutrients did not significantly alter the increase in AST/ALT following LPS. These results indicate that enteral nutrients can decrease liver injury following hemorrhagic hypotension.
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PMID:Enteral feeding minimizes liver injury during hemorrhagic shock. 774 61

Millions of people have been exposed to silicones because of the widespread use in consumer products such as cosmetics and toiletries, food products, household products and paints. Silicones have wide use in medical practice, including lubricants in tubing and syringes, and as implantable devices. The most prevalent silicone in medical use is polydimethylsiloxane. This study was undertaken to determine the subchronic immunotoxicologic potential of the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones did not alter the distribution of B cells and T cells in the spleen, but polyurethane perturbed the distribution of CD4+CD8+ and CD4-CD8- T cells. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, but polyurethane evoked an enhanced phagocytosis of Covaspheres by adherent peritoneal cells. Natural killer cell activity and serum complement were not altered. All silicone materials afforded modest protection to a challenge with Listeria monocytogenes that killed 40 to 58% of control mice. Host resistance to Streptococcus pneumoniae or the B16F10 tumor was not affected by any of the treatments. There is a pattern indicative of some perturbation of T cell differentiation in mice implanted with a polyurethane disk.
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PMID:Subchronic 10 day immunotoxicity of polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 83

Millions of people have been exposed to silicones which are present in consumer goods such as cosmetics and toiletries, processed foods and household products. In addition, silicones have been used extensively in medical practice as a lubricant in tubing and syringes, and as implantable devices. A silicone widely used in medical practice is polydimethylsiloxane. This study was undertaken to determine the immunotoxicologic potential of long term exposure to the principal constituents of breast implants: silicone fluid, silicone gel and silicone elastomer. An alternative covering for devices containing silicone gels, polyurethane, was also included in the study. Silicone fluid and gel were injected subcutaneously into female B6C3F1 mice (1 ml/mouse) and 6 mm disks of silicone elastomer or polyurethane were implanted subcutaneously. There were no treatment-related deaths or overt signs of toxicity during the 180 day exposure. None of the tested materials had notable effects on body or organ weights, erythrocytes or leukocytes in the blood, blood chemistries such as alanine aminotransferase, urea nitrogen, glucose, albumin or total protein, or serum CH 50 or C3 levels. The cellularity of the bone marrow and responses to CSF-GM and CSF-M were normal. The tested silicones and polyurethane marginally reduced the level of Ig+ cells in the spleen but did not consistently alter the distribution of T cell surface markers. The antibody response to sheep erythrocytes was not markedly altered, nor were proliferative responses to concanavalin A, phytohemagglutinin, lipopolysaccharide or allogeneic cells. Reticuloendothelial function was normal, as was phagocytosis of chicken erythrocytes and Covaspheres by adherent peritoneal cells. Natural killer cell activity was depressed in all silicone treatment groups and in mice implanted with polyurethane. No silicone or polyurethane treatment group displayed altered susceptibility to a challenge with Listeria monocytogenes, Streptococcus pneumoniae or the B16F10 tumor. The only consistent effect of 180 day exposure to silicone materials or polyurethane was a modest depression of natural killer cell activity.
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PMID:Immunotoxicity of 180 day exposure to polydimethylsiloxane (silicone) fluid, gel and elastomer and polyurethane disks in female B6C3F1 mice. 798 84


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