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 relationship between the dietary level of vitamin E (VE) and the immune response of broilers was studied in three experiments. Immunity was assessed as antibody production to infectious bronchitis virus (IBV), SRBC, and Brucella abortus (BA) antigens, mitogenic response to phytohemagglutinin A (PHA) and concanavalin A (Con A), cutaneous basophil hypersensitivity (CBH) to PHA, and lipopolysaccharide induction of acute-phase proteins (APP) and heterophilia. A range of VE (0, 10, 17.5, 25, 37.5, 50, 100, and 200 IU/kg) levels were supplemented to a basal diet (corn-soy) containing 10.2 IU of VE/kg. We found a dose-dependent increase in antibody production in response to attenuated IBV between 0 and 25 IU/kg of supplemented VE and no further increase at higher levels. Antibody levels to SRBC were higher in birds supplemented with 50 IU of VE/kg compared to those supplemented with 0 or 200 IU/kg of VE. Antibody production in response to BA antigens was not influenced by VE. Mitogenic responses were suppressed by supplemented VE in Experiment 1 for PHA (25 IU/kg diet) and Con A (25 and 50 IU/kg diets). CBH and APP levels were not affected by VE. Heterophilia was lowest at 50 IU/kg 6 h after lipopolysaccharide injection (Experiment 1). Our study showed that moderate (25 to 50 IU/kg) levels of VE supplementation were most immunomodulatory and that high levels were less effective.
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PMID:Relationship between the level of dietary vitamin E and the immune response of broiler chickens. 1173 76

Inducible nitric oxide (NO) production in macrophages plays an important role in atherosclerosis, the protective effects of vitamin E and its derivatives perhaps being partly mediated by alteration in this parameter. We have investigated the influence of a novel synthesized vitamin E derivative, 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), on NO production in the RAW 264.7 mouse macrophage cell line. HTHQ dose-dependently inhibited lipopolysaccharide (LPS)-induced NO production through reducing LPS-triggered inducible nitric oxide synthase (iNOS) expression. The phosphorylation and subsequent degradation of IkappaB caused by LPS in RAW 264.7 cells was markedly blocked. The free radical scavenging activity of HTHQ was only 2-fold that of vitamin E, whereas its inhibition of NO production was found to be nearly 500-fold stronger. Our results indicated that HTHQ suppressed NO production in macrophages by blocking IkappaB degradation and thus inhibiting iNOS expression. The inhibitory activity of HTHQ on NO production did not parallel its free radical scavenging activity, implying a possible involvement of additional functions.
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PMID:1-O-hexyl-2,3,5-trimethylhydroquinone inhibits IkappaB phosphorylation and degradation-linked inducible nitric oxide synthase expression: beyond antioxidant function. 1190 4

Satisfactory therapy for acute lung injury related to endotoxemia remains to be established. However, in vivo antioxidant treatment with N-acetylcysteine reportedly suppresses acute lung injury and proinflammatory cytokine production induced by endotoxin (lipopolysaccharide, LPS). In addition, intrinsic vitamin E is protective against LPS-induced insults. We determined the effects of a novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), on acute lung injury and mortality induced by LPS in rats. Intravenous injection of TMG (4 or 40 mg/kg) effectively decreased mortality and prevented the increased alveolar permeability and pulmonary edema that were caused by intravenous injection of LPS (20 mg/kg). Treatment with TMG decreased the enhanced lung expression of TNF-alpha caused by LPS. TMG also suppressed the sequestration of neutrophils in the lung induced by LPS. These results indicate that TMG is a possible therapeutic agent for acute lung injury and mortality, especially that caused by gram-negative bacteria. The therapeutic effects could be mediated at least partly through suppression of the increased expression of TNF-alpha and neutrophil sequestration in the lung that are caused by LPS.
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PMID:A novel water-soluble vitamin E derivative, 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol, protects against acute lung injury and mortality in endotoxemic rats. 1246 69

Murine hepatic cytochrome P450 2a5 (Cyp2a5) is induced during hepatotoxicity and hepatitis, however, the specific regulatory mechanisms have not been determined. We compared the influence of acute inflammation elicited in vivo by bacterial endotoxin lipopolysaccharide (LPS) and liver injury caused by the hepatotoxin pyrazole on hepatic Cyp2a5 expression in mice. Pyrazole treatment resulted in statistically significant increases in levels of Cyp2a5 mRNA, protein and catalytic activity by 540, 273 and 711%, respectively (P<0.05). In LPS-treated livers Cyp2a5 expression was significantly reduced compared to controls at the mRNA (46%) protein (35%), and activity (23%) levels (P<0.05). Treatment of mice with recombinant murine interleukin-1 beta and interleukin-6 had no significant effect on Cyp2a5 mRNA and protein levels. Liver injury, as assessed by serum alanine aminotransferase, was greater with pyrazole than with LPS treatment (609 vs 354% of control levels respectively). ER stress, determined by hepatic glucose regulated protein 78 (grp78) levels, was greater with pyrazole (185% of controls) than with LPS (128% of controls). In pyrazole-treated liver, overexpression of immunoreactive grp78 protein revealed that ER stress was localized to pericentral hepatocytes in which Cyp2a5 was induced. Evidence of glycogen loss and membrane damage in these cells was suggestive of oxidative damage. Moreover, vitamin E attenuated Cyp2a5 induction by pyrazole in vivo. These results suggest that induction of Cyp2a5 that has been observed in mouse models of hepatitis and hepatoxicity may be related to oxidative injury to the endoplasmic reticulum of pericentral hepatocytes rather than exposure to pro-inflammatory cytokines.
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PMID:Effects of lipopolysaccharide-stimulated inflammation and pyrazole-mediated hepatocellular injury on mouse hepatic Cyp2a5 expression. 1249 23

Previously, we found that 25 to 50 IU/kg of dietary vitamin E (VE) had very different immunoregulatory effects than high VE levels (200 IU/kg), and we hypothesized that this difference was due to different cytokine profiles. Chicks were fed 0, 30, or 200 IU/kg supplemental VE and percentages of CD4+CD8-, CD4-CD8+, CD4+CD8+, and CD4-CD8- lymphocytes, and the ratio of CD4+/CD8+ lymphocytes was determined. The expression of chicken splenic interleukin-1beta (IL-1beta), myelomonocytic growth factor (MGF), interferon (IFN-gamma), and transforming growth factor-beta (TGFbeta) mRNA was determined by reverse transcription (RT)-PCR after intravenous injection of lipopolysaccharide (LPS). Due to a tendency for increased CD4-CD8+ lymphocytes at 30 IU/kg VE (P=0.072), the CD4+/CD8+ ratio was significantly lower for 30 IU/kg VE compared with 0 IU/kg VE (P=0.041). The VE dose of 200 IU/kg decreased the constitutive (prior to LPS) expression of TGFbeta. The LPS caused an increase in IL-1beta, MGF, and IFNgamma expression at all VE concentrations and had no effect on IL-2 and TGFbeta mRNA expression. Dietary VE decreased MGF mRNA (P=0.049) in a dose-dependent manner but had no effect on the expression of other cytokines. The decreased expression of MGF could explain the immunomodulatory effect of VE in inflammation.
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PMID:Profile of chicken cytokines induced by lipopolysaccharide is modulated by dietary alpha-tocopheryl acetate. 1294 97

1. Various chemokines, such as keratinocyte chemoattractant (KC), macrophage inflammatory protein (MIP)-1alpha and macrophage chemoattractant protein (MCP)-1, are involved in the pathogenesis of acute lung injury induced by bacterial endotoxin (lipopolysaccharide; LPS). Oxidative stress is an important regulator of the expression of these chemokines, whereas vitamin E protects against LPS-induced insults. In the present study, we determined the effects of 2-(alpha-D-glucopyranosyl) methyl-2,5,7,8-tetramethylchroman-6-ol (TMG), a novel water-soluble vitamin E derivative with excellent anti-oxidant activity, on acute lung injury induced by intratracheal instillation of LPS (125 micro g/kg) in mice. 2. When TMG was administered intratracheally and intravenously (0.1, 1.0 or 10 mg/kg), it dose-dependently decreased the infiltration of neutrophils into bronchoalveolar lavage fluid after LPS challenge. 3. Histological examination showed that treatment with TMG ameliorated the LPS-induced infiltration of neutrophils into the lungs. Furthermore, TMG attenuated the LPS-induced increase in pulmonary expression of KC, MIP-1alpha and MCP-1 at both the transcriptional and translational levels. 4. These results indicate that TMG is a possible treatment for acute lung injury, especially that caused by Gram-negative bacteria. The therapeutic effect of TMG may be mediated, at least in part, by suppression of the local expression of chemokines, possibly through its strong anti-oxidant activity.
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PMID:A novel water-soluble vitamin E derivative prevents acute lung injury by bacterial endotoxin. 1505 18

We investigated if a two-hit shock model, commonly referred to as generalized Shwartzman reaction (GSR), can prime for indirect acute respiratory distress syndrome (ARDS) in mice. The GSR was provoked in C57BL/6 mice by two consecutive i.p. injections of 100 microg lipopolysaccharide (LPS) at t = 0 and t = 20 h. These mice demonstrated a dramatic decrease in respiratory capacity and 80% mortality after the second injection. No such effect was observed when LPS was given as a single 200 microg dose at t = 0. Increased expression of proinflammatory cytokines in serum (interleukin-1beta, interleukin-6 and interferon-gamma), lung neutrophilia, and edema formation were observed in mice injected with one dose of LPS, but notably, mice exposed twice did not further increase their inflammatory response. Early treatment 1 h after the first LPS injection (t = 1 h) with either dexamethasone (10 mg/kg) or vitamin E (50 mg/kg) improved respiratory function and down-modulated the induction of proinflammatory cytokines in serum. In conclusion, mice with a generalized Shwartzman reaction exhibited features resembling some aspects of the pathophysiology in septic ARDS, i.e., neutrophilic inflammation, edema formation, impaired respiratory capacity, and mortality. Our data indicate that a systemic cytokine response and lung neutrophilia may prime for the GSR but that other mechanisms account for the rapid decline in lung function after the second challenge. We suggest that this model can be used for studies of pathogenesis and therapeutic prevention of acute respiratory failure.
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PMID:Lung effects during a generalized Shwartzman reaction and therapeutic intervention with dexamethasone or vitamin E. 1548 43

The synthesis of a series of Tocopherol long chain Fatty Alcohols (TFA) and their biological activities on the modulation of microglial activation are described. Specifically, the 2-(12-hydroxy-dodecyl)-2,5,7,8-tetramethyl-chroman-6-ol, the TFA bearing 12 carbon atoms on the side chain (n=12), shows the most potent inhibition of secretion on nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-activated microglia.
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PMID:Tocopherol long chain fatty alcohols decrease the production of TNF-alpha and NO radicals by activated microglial cells. 1554 21

1. Gram-negative bacterial lipopolysaccharide (LPS) release and subsequent septic shock is a major cause of death in intensive care units. Lipopolysaccharide has been reported to increase the production of nitric oxide (NO) and the formation of oxygen-derived free radicals (OFR) in different organs. The aim of the present study was to evaluate the role of an inducible form of NO synthase (iNOS) and OFR production in LPS-induced renal impairment. 2. Measurement of vitamin E as the most important fat-soluble anti-oxidant was used as a marker of tissue oxidative stress. Lipopolysaccharide (10 mg/kg), L-iminoethyl lysine (L-Nil; 3 mg/kg, i.p.; a specific inhibitor of iNOS activity) and dimethyl thiourea (DMTU; 500 mg/kg i.p.; a well-known OFR scavenger) were used. Four groups of eight rats were studied. One group received LPS, whereas a second group received LPS + L-Nil. A third group received LPS + DMTU and the fourth group, receiving saline, acted as a control group. To evaluate renal function, plasma creatinine and blood urea nitrogen (BUN) were measured. High-pressure liquid chromatography and ultraviolet detection were used to measure plasma and tissue vitamin E levels. Light microscopy was used to examine histopathological changes in the four groups. 3. Lipopolysaccharide markedly decreased the vitamin E content of renal plasma and tissue (P < 0.05). Administration of L-Nil attenuated renal dysfunction and preserved vitamin E levels. However, DMTU failed to prevent renal injury, as indicated by plasma BUN levels and renal histology, despite the fact that it maintained renal vitamin E levels and increased plasma vitamin E levels. Thus, the overproduction of NO by iNOS may have a role in this model of LPS-induced renal impairment.
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PMID:Inhibition of inducible nitric oxide synthase reduces lipopolysaccharide-induced renal injury in the rat. 1565 46

Nitric oxide is thought to be an important modulator of various functions in normal and inflamed airways. In the present study, we evaluated the effects of high vitamin E (250 mg and 1250 mg alpha-tocopheryl acetate (TA)/kg diet/10 days) on nitric oxide (NO(.)) release by alveolar macrophages (AMs) in response to lipopolysaccharide (LPS), interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha). LPS and IL-1beta treatment (1-10 microg/ml) enhanced NO(.) release in AMs from control animals fed on 50 mg vitamin E/kg diet in a concentration dependent manner. However, this enhancement of NO(.) was attenuated in the AMs of animals fed with 250 mg or 1250 mg vitamin E/kg diet. TNF-alpha had no effect in eliciting the release of NO(.) in AMs obtained either from control or from hyper vitamin E fed animals. Further, LPS (1-10 microg/ml) enhanced the inducible nitric oxide synthase (iNOS) activity of AMs of control group and TA-fed animals almost to equal extent. Similarly, LPS-induced formation of N-nitrosamine (N-nitroso-L-[(14)C]-proline) in AMs of control and TA-supplemented animals were not different statistically. On the other hand, in vitro addition of vitamin E (200 microM) in AMs of control animals, when triggered with 10 microg LPS/ml, caused a significant decrease in N-nitroso-L-[(14)C]-proline formation. It seems that high doses of TA in diet may play a role in reducing the lipopolysaccharide and proinflammatory cytokines-induced NO(.)-mediated damage by AMs.
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PMID:Inhibitory effect of vitamin E on proinflammatory cytokines-and endotoxin-induced nitric oxide release in alveolar macrophages. 1579 34


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