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)

Lipid A is the lipophilic moiety of lipopolysaccharides (LPSs), the major components of the external membrane of almost all gram-negative bacteria. It is responsible for the toxicity of LPS and has a heterogeneous structure composed of a bis-phosphorylated glucosamine disaccharide backbone that is acylated at the positions 2, 3 of the GlcN I (proximal) and GlcN II (distal) residue with O- and N-linked 3-hydroxy fatty acids (primary substitution). These fatty acids are further acylated by means of their 3-hydroxy groups (secondary substitution). The toxicity of Lipid A is dependent on its primary structure; the number, the length, and the distribution of the fatty acids on the disaccharide backbone strongly influence the endotoxic activity. In this paper a general and easy methodology to obtain secondary fatty acid distribution, which is one of the most difficult issues in the structural determination of Lipid A, is proposed. The method combines ammonium hydroxide hydrolysis and matrix assisted laser desorption ionization (MALDI)-mass spectrometry analysis and has been successfully proven with five different Lipid A species. The procedure exploits the lower stability under mild alkaline conditions of acyl and acyloxyacyl esters with respect to that of the acyl and acyloxyacyl amides. The partially degraded Lipid A species obtained are analyzed by MALDI-MS. The generality of this approach was tested on five Lipid As, namely those arising from Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas reactans, and Burkholderia caryophylli.
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PMID:Ammonium hydroxide hydrolysis: a valuable support in the MALDI-TOF mass spectrometry analysis of Lipid A fatty acid distribution. 1245 82

Robinet, Harriette G. (Walter Reed Army Institute of Research, Washington, D.C.). Relationship of host antibody to fluctuations of Escherichia coli serotypes in the human intestine. J. Bacteriol. 84:896-901 1962.-A study was undertaken to determine the relationship of host antibody to the changes which take place among Escherichia coli serotypes present in the intestine. A survey of six healthy persons examined for E. coli monthly for 6 months reaffirmed the periodic fluctuations of antigenic types. Serotypes were studied from each individual and their appearance and maintenance or disappearance closely followed. Representative strains were chosen each month and used to prepare a heated sodium hydroxide lipopolysaccharide extract for sensitizing human group O Rh-negative red blood cells for the hemagglutination test. These antigens were tested with the sera drawn from each of the six individuals at the time monthly cultures were made. Results showed that antibody levels for each serotype remained basically constant over the 6-month period. Titer levels tended to be characteristic of the host rather than related to the E. coli bacteria, as shown by tests with serotypes both from the individual's own intestinal tract and from other individuals in the study. High normal antibody levels for autologous E. coli serotypes did not act as a deterrent to the ability of the organisms to establish themselves in the bowel, nor did antibody titer for E. coli strains determine whether they would continue as residents over several months or depart as transient flora.
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PMID:Relationship of host antibody to fluctuations of Escherichia coli serotypes in the human intestine. 1397 1

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (KL-1156) is a novel chemically synthetic compound. In the present study, the chroman KL-1156 compound was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide production in macrophages RAW 264.7. KL-1156 compound attenuated LPS-induced synthesis of both mRNA and protein of inducible nitric oxide synthase (iNOS), in parallel, and inhibited LPS-induced iNOS promoter activity, indicating that the chroman compound down-regulated iNOS expression at transcription level. As a mechanism of the anti-inflammatory action shown by KL-1156 compound, suppression of nuclear factor (NF)-kappaB has been documented. KL-1156 compound exhibited a dose-dependent inhibitory effect on LPS-induced NF-kappaB transcriptional activity in macrophages RAW 264.7. Furthermore, the compound inhibited LPS-induced nuclear translocation of NF-kappaB p65 and DNA binding activity of NF-kappaB complex, in parallel, but did not affect IkappaBalpha degradation. Taken together, this study demonstrated that chroman KL-1156 compound interfered with nuclear translocation step of NF-kappaB p65, which was attributable to its anti-inflammatory action.
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PMID:Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-kappaB activation. 1552 22

6-Hydroxy-7-methoxychroman-2-carboxylic acid phenylamide (CP compound) is a novel chemically synthetic compound with vitamin E-like chemical structure. In the present study, the CP compound was discovered to inhibit nitric oxide (NO) and interleukin (IL)-6 productions in lipopolysaccharide (LPS)-stimulated macrophages. Further, CP compound attenuated LPS-induced synthesis of mRNA and protein levels of inducible NO synthase (iNOS), in parallel, and inhibited iNOS promoter activity. In the similar way, CP compound inhibited LPS-induced synthesis of IL-6 transcript but also IL-6 promoter activity. These results indicate that CP compound could down-regulate LPS-induced iNOS and IL-6 expression at the transcription step. As a mechanism of the anti-inflammatory action shown by CP compound, suppression of LPS-induced activation of both nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) has been documented. Finally, CP compound could provide an invaluable tool to investigate LPS-induced NF-kappaB and AP-1 activation, in addition to its therapeutic potential in NO- and IL-6-associated inflammatory diseases.
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PMID:Inhibitory effect of 6-hydroxy-7-methoxychroman-2-carboxylic acid phenylamide on nitric oxide and interleukin-6 production in macrophages. 1597 34

The rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay have been used to detect endotoxins in vaccines, but interactions between the endotoxins and proteins or aluminum hydroxide can interfere with the results. Currently, the rabbit pyrogen test is used to detect endotoxin in hepatitis B (HB) vaccines even though the HB surface protein, the active ingredient, is over-expressed in and purified from eukaryotic cells which lack endotoxin. Therefore, we examined the possibility of replacing the animal tests with the more efficient LAL test. To this end, we determined whether the aluminum hydroxide in the HB vaccines affects the rabbit pyrogen test and the LAL assay. HB vaccines and HB protein solutions spiked with lipopolysaccharide (LPS) produced almost the same dose-dependent temperature rise in rabbits, indicating that the aluminum hydroxide in the HB vaccine does not interfere with the pyrogenic response in rabbit. In contrast, a spike recovery study showed that aluminum hydroxide interfered with the LAL clot and kinetic assays; however, the LAL clot assay was effective at detecting endotoxin without loss of LAL activity after serial dilution of the samples. Furthermore, there was good correlation in the LAL clot assay between the amount of LPS added and the amount recovered. However, both turbidimetric and chromogenic kinetic assays displayed no correlation between the LPS amount added and recovered. Our results suggest that the LAL clot assay is sensitive and reliable when samples are properly prepared, and can be used to replace the rabbit pyrogen test for the detection of endotoxin in HB vaccines.
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PMID:Comparison of the rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay for endotoxin in hepatitis B vaccines and the effect of aluminum hydroxide. 1605 44

In this study, the haemolytic activities of Bupleurum chinense saponins (BCS) and its adjuvant potentials on the immune responses of ICR mice against ovalbumin (OVA) were evaluated. BCS showed a slight haemolytic effect, with its haemolytic percents being 3.32% and 1.19% at the concentrations of 500 and 250 microg/ml, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing aluminium hydroxide gel (Alum, 200 microg), QuilA (10 and 20 microg) or BCS (50, 100 or 200 microg) on Days 1 and 15. Two weeks later (Day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. BCS significantly enhanced the Con A-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice especially at a dose of 100 microg (P<0.05 or P<0.001). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by BCS compared with OVA control group (P<0.01 or P<0.001). Moreover, no significant differences (P>0.05) were observed between enhancing effect of BCS and QuilA on the OVA-specific IgG2b antibody responses to OVA in mice. In conclusion, the results suggest that BCS could be safely used as adjuvant with low or non-haemolytic effect.
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PMID:Haemolytic activities and adjuvant effect of Bupleurum chinense saponins on the immune responses to ovalbumin in mice. 1621 70

In this study, the haemolytic activities of Gynostemma pentaphyllum saponins (GPS) and its adjuvant potential on the immune responses of ICR mice against ovalbumin (OVA) were evaluated. GPS showed a slight haemolytic effect, with its haemolytic activity being 10.20% and 4.90% at concentrations of 500 and 250 microg/mL, respectively. ICR mice were immunized subcutaneously with OVA 100 microg alone or with OVA 100 microg dissolved in saline containing aluminium hydroxide gel (Alum, 200 microg), QuilA (10 and 20 microg) or GPS (50, 100 or 200 microg) on days 1 and 15. Two weeks later (day 28), concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. GPS significantly enhanced the Con A-, LPS- and OVA-induced splenocyte proliferation in the OVA-immunized mice, especially at a dose of 100 microg (p < 0.05 or p < 0.001). OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by GPS compared with the OVA control group (p < 0.05, p < 0.01 or p < 0.001). In conclusion, the results suggest that GPS could be used safely as an adjuvant with low or no haemolytic effect.
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PMID:Haemolytic activities and adjuvant effect of Gynostemma pentaphyllum saponins on the immune responses to ovalbumin in mice. 1626 22

Net acid-generating capacities of 39.74 kg of H(2)SO(4) per ton (ca. 0.05 kg/kg) (pH 2.68) for the Lemoine copper mine tailings (closed ca. 8 years ago; located 40 km west of Chibougamau, Quebec, Canada) and 16.07 kg of H(2)SO(4) per ton (ca. 0.02 kg/kg) (pH 3.01) for the Copper Rand tailings (in current use and 50 km distant [east] from those of Lemoine) demonstrate that these sulfide tailings can support populations of acidophilic thiobacilli. Oxidized regions in both tailings environments were readily visible, were extremely acidic (Lemoine, pH 2.36; Copper Rand, pH 3.07), and provided natural isolates for our study. A 10% (wt/vol) oxalic acid treatment, which solubilizes both ferric sulfate and ferric hydroxide precipitates (B. Ramsay, J. Ramsay, M. deTremblay, and C. Chavarie, Geomicrobiol. J. 6:171-177, 1988), enabled the recovery of intact bacterial cells from the tailings material and from liquid synthetic medium for lipopolysaccharide analysis. No viable cells could be cultured after this oxalic acid treatment. Sodium dodecyl sulfate-polyacrylamide gel electro-phoretic profiles of lipopolysaccharides extracted from the Lemoine tailings were complex, indicating a heterogeneous population of Thiobacillus ferrooxidans. Six T. ferrooxidans subspecies as identified by lipopolysaccharide analysis (i.e., lipopolysaccharide chemotypes) were eventually isolated from a total of 112 cultures from the Lemoine tailings. Using the same isolate and lipopolysaccharide typing techniques, we identified only a single lipopolysaccharide chemotype from 20 cultures of T. ferrooxidans isolated from the Copper Rand tailings. This homogeneity of lipopolysaccharide chemotype was much different from what was found for the older Lemoine tailings and may reflect a progressive lipopolysaccharide heterogeneity of Thiobacillus isolates as tailings leach and age.
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PMID:Examination of Lipopolysaccharide (O-Antigen) Populations of Thiobacillus ferrooxidans from Two Mine Tailings. 1634 25

6-Hydroxy-7-methoxychroman-2-carboxylic acid (3-nitrophenyl)amide (CP-1158) is a synthetic chroman carboxamide with trolox-like chemical structure. In the present study, CP-1158 was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The CP-1158 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity. Further, CP-1158 attenuated LPS-induced syntheses of tumor necrosis factor (TNF)-alpha, IL-1beta, interferon-inducible protein (IP)-10 and macrophage inflammatory protein (MIP)-1beta transcripts. Nuclear factor (NF)-kappaB has been evidenced to play a major mechanism in LPS-induced expression of IL-6 or other inflammatory cytokines. CP-1158 prevented LPS-induced nuclear translocation of NF-kappaB complex and subsequently inhibited DNA binding activity of NF-kappaB complex as well as NF-kappaB transcriptional activity in macrophages RAW 264.7. However, CP-1158 did not affect LPS-induced phosphorylation and degradation of inhibitory kappaB (IkappaB). In another experiment, CP-1158 inhibited IL-6 promoter activity elicited by expression vectors encoding NF-kappaB p50 or p65 subunit. Taken together, CP-1158 inhibited LPS-induced expression of inflammatory cytokines including IL-6, targeting NF-kappaB activating pathway downstream IkappaB degradation, and thus could provide an anti-inflammatory potential of chroman carboxamide.
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PMID:Inhibitory effect of chroman carboxamide on interleukin-6 expression in response to lipopolysaccharide by preventing nuclear factor-kappaB activation in macrophages. 1679 5

Macrophage cyclooxygenase-2 (COX-2) plays an important role in prostaglandin E2 and thromboxane A2 production. Statins are inhibitors of HMG CoA (3-Hydroxy-3-methylglutaryl coenzyme A) reductases and cholesterol synthesis, which block the expression of several inflammatory proteins independent of their capacity to lower endogenous cholesterol. In the present study, we investigated the effect of simvastatin and mevastatin on COX-2 induction in human monocytic cell line U937 and analyzed the underlying mechanisms. Pretreatment of U937 cells with simvastatin or mevastatin for 24 h resulted in a significant reduction in the lipopolysaccharide (LPS)-dependent induction of prostaglandin E2, thromboxane A2 synthesis, and COX-2 expression. Mevalonate, the direct metabolite of HMG CoA reductase, and farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, intermediates of the mevalonate pathway, significantly reversed the inhibitory effect of statins on COX-2. An inhibitor of geranylgeranyl transferases, GGTI-286 mimicked the effect of statins on COX-2 expression. Cytonecrotic factor-1 increased LPS-dependent expression of COX-2. Treatment of cells with NSC 23766, an inhibitor of Rac, which we demonstrated to block Rac 2 activation, resulted in an inhibition of the LPS-dependent expression of COX-2. Whereas no effect was obtained with RhoA/C blocker, C3 exoenzyme. Gel retardation experiments and NFkappaB-p65 transcription factor assay showed that simvastatin and NSC 23766 decrease significantly NF-kappaB complex formation. In macrophages, the antiinflammatory effects of statins are mediated in part through the inhibition of COX-2 and prostanoids. Rac GTPase protein is identified as one of the targets of statins in this regulation.
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PMID:Modulation of COX-2 expression by statins in human monocytic cells. 1731 25


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