UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stimulation of human polymorphonuclear leucocytes (PMN) with phagocytosable particles [yeast-IgG (Y-IgG)], lipopolysaccharide (LPS), tumour necrosis factor (TNF) or formyl-methionyl-leucyl-phenyl-alanine (FMLP) results in an increase of the interleukin-8 (IL-8) mRNA accumulation and a subsequent release of the protein. Here, we report that interferon-gamma (IFN-gamma) down-regulates the constitutive IL-8 mRNA levels expressed by resting PMN. As shown by Northern analysis, this down-modulation occurred rapidly, was not dependent on new protein synthesis, and was not caused by an increased rate of degradation of IL-8 mRNA. Preincubation of PMN with IFN-gamma significantly inhibited their ability to release IL-8 upon stimulation with TNF, LPS, FMLP and Y-IgG, but enhanced the respiratory burst capability in response to FMLP and TNF. TNF-, LPS- and FMLP-induced expression of IL-8 mRNA was also selectively inhibited by IFN-gamma. Taken together these findings suggest that IFN-gamma has important regulatory effects on acute inflammatory response because of its capacity to modulate negatively IL-8 gene expression and secretion by human PMN. Further observations revealed that, in human PMN, degradation of IL-8 mRNA is finely regulated, and that cycloheximide (CHX), an inhibitor of protein synthesis, super-induces the mRNA accumulation for IL-8 in a dose- and time-dependent manner.
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PMID:Interferon-gamma inhibits interleukin-8 production by human polymorphonuclear leucocytes. 847 10

Structural characteristics of peptidoglycan fragments required to prime mice for the induction of anaphylactoid reactions by Salmonella abortusequi lipopolysaccharide were examined in endotoxin-resistant C3H/HeJ mice, with special focus on the disaccharide-pentapeptide [N-acetylglucosaminyl-beta(1-4)-N-acetylmuramyl-L-alanyl-D -isoglutaminyl-meso-2,6-diaminopimelyl (DAP)-D-alanyl-D -alanine] and its smaller partial derivatives. The bacterial and synthetic muramyl tripeptides (DAP- and lysine [Lys]-type, respectively) and synthetic muramyl dipeptide primed mice for induction of anaphylactoid reactions accompanied by death within 1 h. The disaccharide-tripeptide exhibited weaker activity, and the disaccharide-tetrapeptide and muramyl tetrapeptide exhibited marginal activity. In contrast, intact peptidoglycans of various bacteria and the disaccharide-pentapeptide lacked the priming activity, although they showed adjuvant activity similar to that of the above components.
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PMID:Structural characteristics of peptidoglycan fragments required to prime mice for induction of anaphylactoid reactions by lipopolysaccharides. 855 Feb 22

The objective of this study was to elucidate the role of the proteasome pathway or multicatalytic proteinase complex in the induction of immunologic nitric oxide (NO) synthase (iNOS) in rat alveolar macrophages activated by lipopolysaccharide. Macrophages were incubated in the presence of lipopolysaccharide plus test agent for up to 24 hr. Culture media were analyzed for accumulation of stable oxidation products of NO (NO2- + N03-, designated as NOX-), cellular RNA was extracted for determination of iNOS mRNA levels by Northern blot analysis, and nuclear extracts were prepared for determination of NF-kappa B by electrophoretic mobility-shift assay. Inhibitors of calpain (alpha-N-acetyl-Leu-Leu-norleucinal; N-benzyloxycarbonyl-Leu-leucinal) and the proteasome (N-benzyloxycarbonyl-Ile-Glu-(O-t-Bu)-Ala-leucinal) markedly inhibited or abolished the induction of iNOS in macrophages. The proteinase inhibitors interfered with lipopolysaccharide-induced NOX- production by macrophages, and this effect was accompanied by comparable interference with the appearance of both iNOS mRNA and NF-kappa B. Calpain inhibitors elicited effects at concentrations of 1-100 microM, whereas the proteasome inhibitor was 1000-fold more potent, producing significant inhibitory effects at 1 nM. The present findings indicate that the proteasome pathway is essential for lipopolysaccharide-induced expression of the iNOS gene in rat alveolar macrophages. Furthermore, the data support the view that the proteasome pathway is directly involved in promoting the activation of NF-kappa B and that the induction of iNOS by lipopolysaccharide involves the transcriptional action of NF-kappaB.
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PMID:Inhibitors of the proteasome pathway interfere with induction of nitric oxide synthase in macrophages by blocking activation of transcription factor NF-kappa B. 862 34

After stimulation with select activating agents such as lipopolysaccharide (LPS) or recombinant interferon-gamma (rIFNgamma), several macrophage proteins may be induced, acylated with myristic acid, or both. Our goal in this study was to determine whether altering the levels of myristic acid in the diet would modulate the levels of a specific acylated macrophage protein, MacMARCKS (myristoylated, alanine-rich C kinase substrate), because that fatty acid can be found in substantial quantities in some foods. Thioglycollate-elicited peritoneal macrophages from groups of mice fed diets with various levels of myristic acid (from 0.2 to 99 g/100 g fatty acids) were treated with LPS, phorbol myristate acetate (PMA), or rIFNgamma plus LPS, which are well-established macrophage activating agents. Levels of MacMARCKS were measured by enzyme-linked immunosorbent assay using a rabbit anti-mouse polyclonal antibody against the first 10 amino acids of murine MacMARCKS. A 42-kDa protein with the same molecular weight as MacMARCKS was identified in macrophage lysates by Western analysis using the antibody. Lipopolysaccharide- and PMA-activated macrophages from mice fed the trimyristin diet had significantly greater levels of MacMARCKS than LPS- and PMA-activated macrophages of mice fed the safflower oil-containing diet. The levels of MacMARCKS were also greater in lysates of LPS plus rIFNgamma-stimulated macrophages from mice fed the trimyristin diet and mice fed a diet containing a moderate level of myristic acid (12 g/100 g fatty acids) compared with the lysates of macrophages from mice fed the safflower oil diet. These results indicate that altering the level of myristic acid in the diet may alter the production of specific proteins that may be involved in macrophage activation.
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PMID:Dietary myristic acid alters acylated proteins in activated murine macrophages. 864 29

rBPI23 is a biologically active, recombinant N-terminal fragment of human bactericidal/permeability-increasing protein (BPI). While rBPI23 is readily purified from culture supernatants of Chinese hamster ovary (CHO)-K1 transfectants, it is heterogeneous, consisting of monomer and disulfide-linked dimer, characteristics due presumably to the presence of three cysteines within the molecule. We have examined the role of these cysteines in rBPI23 expression, function, and dimer formation by mutating their codons to alanine (C132A), serine (C135S), or alanine (C175A) and expressing analogues of N-terminal fragments ("variants") lacking one, two, or all three cysteines in permanently transfected CHO-K1 cells. We also expressed a variant in which serine 18 was changed to cysteine (S18C), as found in both bovine and rabbit BPI. The C132A variant was readily secreted and purified as a homogeneous, stable monomeric protein species. The C135S and S18C variants were produced as mixtures of monomer and dimer; the C135S variant was poorly secreted, difficult to purify, and unstable on storage. In contrast, the C175A variant and those lacking any two or all three cysteines were expressed but not secreted. Purified rBPI23 and the C132A and S18C variants had comparable bactericidal and lipopolysaccharide (LPS) binding activities and were similarly effective at neutralizing LPS-induced tumor necrosis factor synthesis by THP-1 cells; the purified C135S variant lacked all activities. From these studies with CHO-K1 transfectants, we conclude that (i) cysteines 135 and 175 are both necessary for efficient secretion of a biologically active N-terminal BPI fragment, presumably through the formation of a disulfide bond, (ii) cysteine 132 is responsible for dimer formation, and (iii) only the C132A modification yields a stable, biologically active, N-terminal BPI fragment (designated rBPI21) that is free of dimeric species.
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PMID:Expression and characterization of cysteine-modified variants of an amino-terminal fragment of bactericidal/permeability-increasing protein. 881 32

A model for an alpha-helical peptide library based on a lactam bridged stabilized two-stranded alpha-helical coiled-coil is described. Sites for library display were incorporated in the middle of the peptide sequence of the most solvent accessible sites of a coiled-coil. A comparison was made between this coiled coil and a native coiled-coil based on the same sequence but lacking the lactam bridges. A lactam bridged peptide where the hydrophobic repeat consisted of all alanine residues, such that the tendency to dimerize would be diminished, was also prepared. This enabled us to determine the role tertiary interactions play in maintaining library positions in a helical conformation. The consensus sequence derived from a Zn finger library screened against an IgA reactive against the lipopolysaccharide of Shigella flexneri was transplanted into the peptides. CD spectroscopy revealed that although both coiled-coils are highly helical at 100 microM, the lactam bridge enhanced dimerization and allow the peptide to maintain its coiled-coil conformation at lower peptide concentrations. The helical content of the alanine based peptide was 69% and was independent of concentration over a range of 1.4 to 1410 microM. Urea denaturation studies indicated that the coiled-coils were considerably more stable than the alanine based peptide and that the lactam bridge coiled-coil was more stable than the native coiled coil by 1.6 kcal/mol. The lactam bridged coiled-coil was found to inhibit binding of the Zn finger peptide to the IgA in a concentration dependent manner with an IC50 of 5.0 microM whereas the peptide lacking the lactam bridges was much less effective in inhibiting binding. The alanine peptide was less active than the lactam bridged coiled-coil but more effective than the native coiled-coil with an IC50 of 16 microM. The versatility of the lactam stabilized coiled-coil template was demonstrated by incorporating five Gly residues into the library display sites. While the native coiled-coil adopted a random conformation the lactam bridged coiled-coil was 59% helical. Incorporation of a Cys-Gly-Gly linker to the N terminus and formation of a disulfide bond stabilized the peptide to the extent that it adopted a highly helical coiled-coil (94%) with a [urea]1/2 value of 5.9 M. Since the five glycine residues represent one of the most destabilizing combinations of amino acids that would be encountered at the five library display sites (with the exception of Pro), this stabilized coiled-coil should maintain its folded conformation regardless of the amino acids occupying the library positions.
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PMID:Use of a conformationally restricted secondary structural element to display peptide libraries: a two-stranded alpha-helical coiled-coil stabilized by lactam bridges. 883 93

When administered with D-galactosamine, lipopolysaccharide endotoxins produce a good experimental animal model of hepatitis. This galactosamine plus endotoxin model has been used widely, but the acute effect of this fixed combination of two chemicals on hepatic and extrahepatic biotransformation has not been determined. Therefore, either 2 or 4 hr after a single intraperitoneal dose of 300 mg/kg galactosamine plus 30 micrograms/kg lipopolysaccharide was administered, serum, liver, kidney, intestine, and spleen were collected. Serum enzymes (alanine and aspartate aminotransferases, sorbitol dehydrogenase, and gamma-glutamyltranspeptidase) were elevated dramatically 2 and 4 hr after treatment. Cytochrome P450 monooxygenase activity toward benzo-[a]pyrene was increased in kidney 4 hr after treatment, whereas dealkylation of 7-methoxycoumarin or 7-ethoxyresorufin was unchanged in any tissue at either time point. An increase in UDP-glucuronosyltransferase activity toward 4-methylumbelliferone and 4-hydroxybiphenyl was noted in the intestine. Conjugation of 1-chloro-2,4-dinitrobenzene with glutathione was increased in intestine and spleen 2 hr after treatment. gamma-Glutamyltranspeptidase activity was unaltered in all tissues studied. Reduced glutathione concentrations were increased significantly by different amounts depending on which organs were studied 2 or 4 hr after treatment. These results indicate that galactosamine/lipopolysaccharide-induced liver injury is not accompanied by major effects on the examined biotransformation reactions.
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PMID:Minimal effect of acute experimental hepatitis induced by lipopolysaccharide/D-galactosamine on biotransformation in rats. 895 52

Lipopolysaccharide was isolated from dry biomass of the Pseudomonas fluorescens strain IMV 472 (biovar I) by the Westphal procedure and purified by ultracentrifugation. Fractions of the structural components of the lipopolysaccharide macromolecule-lipid A, the core oligosaccharide, and the O-chain-were isolated and characterized. 3-Hydroxydecanoic, 2-hydroxydodecanoic, 3-hydroxydodecanoic, hexadecenoic, octadecenoic, and hexadecanoic acids were identified as the main fatty acids of lipid A. The hydrophilic moiety of lipid A was found to include glucosamine, phosphoethanolamine, and phosphate. Glucose, galactose, rhamnose, glucosamine, galactosamine, alanine, phosphoethanolamine, and 2-keto-3-deoxyoctulosonic were identified in the core region of lipid A. The O-specific polysaccharide chain consisted of a repeating tetrasaccharide fragment that included two L-rhamnose residues, a D-fucose residue, and an N-acetyl-D-glucosamine residue as a side substituent. Double immunodiffusion in agar and the lipopolysaccharide precipitation reaction revealed no serological interrelation between strain IMV 472 and P. fluorescens strains studied previously.
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PMID:[Characterization of the lipopolysaccharide from the Pseudomonas fluorescens strain IMV 472 (biovar I)]. 899 40

Recent studies demonstrate that taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) and other proinflammatory mediators in cultured macrophages when added to the media at the time of activation. Because Tau-Cl may react with various media constituents and it is difficult to measure Tau-Cl in complex solutions, we designed experiments to more carefully control cell exposure to various chloramines and NaOCl. RAW 264.7 cells were exposed to 1 mM of NaOCl, Tau-Cl, or chloramine preparations of the following amino acids: L-alanine (L-Ala-Cl), beta-alanine (beta-Ala-Cl), serine (Ser-Cl), or glycine (Gly-Cl) in Hanks' balanced salt solution (HBSS) for up to 2 h (37 degrees C, 5% CO2). The HBSS solution was then replaced with complete media containing interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) for an additional 24 h before measuring cell viability. The chemical stability of NaOCl and each chloramine was evaluated after various times of preactivation exposure by measuring retention of each solution's UV absorption spectra and ability to oxidize KI. Cytotoxicity of each solution was evaluated by the maintained ability of RAW 264.7 cells to reduce MTT. Whereas Tau-Cl, beta-Ala-Cl, and Gly-Cl were stable chloramines, only Tau-Cl was not cytotoxic. L-Ala-Cl, Ser-Cl, and the highly reactive oxidant NaOCl were unstable and toxic. In further studies RAW 264.7 cells were exposed to Tau-Cl in HBSS for 2 h and the solution was then replaced with complete media containing IFN-gamma and LPS, taxol, lipoarabinomannan, or interleukin-2. Production of NO was measured 24 h later and was inhibited in activated cells that were previously exposed to Tau-Cl. Inhibition of NO production was dependent on Tau-Cl concentration and was accounted for by reduced expression of inducible nitric oxide synthase mRNA, regardless of activator combinations. These results support the idea that Tau-Cl has the potential to function as an inhibitory modulator of inflammations.
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PMID:Preactivation exposure of RAW 264.7 cells to taurine chloramine attenuates subsequent production of nitric oxide and expression of iNOS mRNA. 902 21

As a key receptor for lipopolysaccharide (LPS) on the surface of monocytes and macrophages, the CD14 molecule is primarily involved in non-specific host defense mechanisms against gram-negative bacteria. To delineate the structural basis of LPS binding, 23 mutants in the N-terminal 152 amino acids of human CD14 were generated and stably transfected into CHO cells. In each mutant, a block of five amino acids was substituted by alanine. Reactivity of the mutants with anti-CD14 mAbs, and their ability to interact with LPS and Escherichia coli were tested. 4 of 21 expressed CD14 mutants, ([Ala9-Ala13]CD14, [Ala39-Ala41, Ala43, Ala44]CD14, [Ala51-Ala55]CD14 and [Ala57, Ala59, Ala61-Ala63]CD14), are not recognized by anti-CD14 mAbs that interfere with the binding of LPS to human monocytes. However, only [Ala39-Ala41, Ala43, Ala44]CD14 is unable to react with fluorescein-isothiocyanate-labeled LPS or with FITC-labeled E. coli (055:B5). In addition, [Ala39-Ala4l, Ala43, Ala44]CD14 does not mediate LPS (E. coli 055:B5; 10 ng/ml)-induced translocation of nuclear factor kappaB in CHO-cell transfectants. The results indicate that the region between amino acids 39 and 44 forms an essential part of the LPS-binding site of human CD14.
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PMID:Mutation of amino acids 39-44 of human CD14 abrogates binding of lipopolysaccharide and Escherichia coli. 903 Jul 27

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