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)

S-nitro-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, inactivated bovine glutathione peroxidase (GPx) in a dose- and time-dependent manner. The IC50 of SNAP for GPx was 2 microM at 1 h of incubation and was 20% of the IC50 for another thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase, in which a specific cysteine residue is known to be nitrosylated. Incubation of the inactivated GPx with 5 mM dithiothreitol within 1 h restored about 50% of activity of the start of the SNAP incubation. A longer exposure to NO donors, however, irreversibly inactivated the enzyme. The similarity of the inactivation with SNAP and reactivation with dithiothreitol of GPx to that of glyceraldehyde-3-phosphate dehydrogenase, suggested that NO released from SNAP modified a cysteine-like essential residue on GPx. When U937 cells were incubated with 100 microM SNAP for 1 h, a significant decrease in GPx activity was observed although the change was less dramatic than that with the purified enzyme, and intracellular peroxide levels increased as judged by flow cytometric analysis using a peroxide-sensitive dye. Other major antioxidative enzymes, copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase, were not affected by SNAP, which suggested that the increased accumulation of peroxides in SNAP-treated cells was due to inhibition of GPx activity by NO. Moreover, stimulation with lipopolysaccharide significantly decreased intracellular GPx activity in RAW 264.7 cells, and this effect was blocked by NO synthase inhibitor N omega-methyl-L-arginine. This indicated that GPx was also inactivated by endogenous NO. This mechanism may at least in part explain the cytotoxic effects of NO on cells and NO-induced apoptotic cell death.
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PMID:Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity. 767 30

When rabbit alveolar macrophages were treated with phorbol-12-myristate-13-acetate (PMA) and lipopolysaccharide (LPS), the synthesis of interleukin-1 (IL-1), as well as tumor necrosis factor (TNF), was greatly increased. These inducible cytokines were subjected to cloning by the differential colony hybridization method and the subsequent mRNA hybridization-translation assay. Cloned rabbit IL-1 cDNA was disclosed to encode the sequence of the counterpart of the mouse IL-1 alpha. This cDNA was used as a hybridization probe to screen a human cDNA library which was constructed from induced HL-60 cells, a human promyelocytic leukemia cell line. Isolated human IL-1 alpha cDNA was shown to direct the synthesis of a polypeptide with IL-1 activity in E. coli expression system. The chromosomal gene for human IL-1 alpha was isolated and characterized to elucidate the structural organization of this gene. To identify the region that is essential for regulating IL-1 alpha gene expression, various CAT (chloramphenicol acetyltransferase) fusion plasmids were constructed and analysed for their ability to direct CAT synthesis in a transient expression system. The unpublished results obtained in the early stages of these experiments are also presented and discussed in this review.
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PMID:Molecular studies on interleukin-1 alpha. 772 86

Cellular adherence is important for monocyte migration and function and is known to induce monocyte activation, leading to the production of mRNA for several proto-oncogenes and cytokines. In addition, since cellular adherence has important intracellular signalling function, it has the potential to enhance human immunodeficiency virus (HIV) replication in monocytic cells. We have investigated the effects of adhesion of the monocytic cell line THP-1 transfected with HIV1 or HIV2 long terminal repeat chloramphenicol acetyltransferase (LTR CAT) constructs. These studies have shown that adherence to tissue culture plastic or confluent endothelial cells is essential for enhanced HIV LTR CAT expression in lipopolysaccharide-stimulated cells. In addition, we have investigated the effects of engagement of specific adhesion molecules, using immobilized antibodies, on HIV replication in the promonocytic cell line OM101, which contains a single latent proviral copy of HIV. Such studies have demonstrated that engagement of CD18, the beta subunit of the lymphocyte function-related antigen-1 (LFA-1) and major histocompatibility complex class II (MHC II) enhanced HIV replication. LFA-1 is involved in both monocyte-endothelial cell interactions and monocyte-T-cell interactions, and MHC II is involved in monocyte interaction with antigen-specific T cells. These data suggest that such interactions of membrane adhesion molecules with their appropriate ligand enhance HIV replication in vivo. Thus, this study has demonstrated that cellular adherence is a key regulatory factor of HIV replication in monocytic cells.
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PMID:Cellular adherence enhances HIV replication in monocytic cells. 780 Sep 38

Thioglycolate-elicited murine macrophages from genetically susceptible A/J mice activated with lipopolysaccharide (LPS) and infected with Legionella pneumophila in vitro evince marked inhibition of intracellular growth of this bacterium. The mechanism of inhibition by LPS-activated macrophages in terms of replication of this intracellular pathogen is unclear. LPS activation of murine macrophages induced a downshift in transferrin receptor (TfR) expression and reduction in cellular iron content, and this was correlated with augmented intracellular growth of Legionella in the cells. When LPS-stimulated macrophages were first saturated with iron, partial reversion of L. pneumophila growth restriction was observed. However, an excess of exogenous L-tryptophan (Trp) did not reverse this growth inhibition, nor did supplementation of the macrophage culture medium with both iron and Trp. The antilegionella activity of the macrophages induced by LPS activation was independent of reactive oxygen intermediates (ROI), since the scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on growth restriction. Likewise, notwithstanding the ability of LPS-activated macrophages to synthesize reactive nitrogen intermediates (RNI), which was inhibited by L-arginine analogs NG-monomethyl-L-arginine and L-aminoguanidine), as well as by incubation in arginine-free medium, their ability to inhibit the intracellular replication of L. pneumophila was not affected. Thus, we conclude that LPS-activated macrophages inhibit the intracellular growth of L. pneumophila partially by iron-dependent, Trp-independent, and ROI- and RNI-independent mechanisms. We also suggest that additional unknown mechanisms are involved, since complete reversion was not obtained.
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PMID:LPS inhibits the intracellular growth of Legionella pneumophila in thioglycolate elicited murine peritoneal macrophages by iron-dependent, tryptophan-independent, oxygen-independent, and arginine-independent mechanisms. 782 75

Using a rat lung organ culture system, we analyzed the role of monocyte chemoattractant protein 1 (MCP 1) in leukocyte to lung adhesive interactions and monocyte-mediated lung injury. Quantitative leukocyte to lung adhesive interactions were examined using an adaptation of the Woodruff-Stamper frozen section binding assay. Pretreatment of organ cultures with recombinant human tumor necrosis factor (rhTNF alpha) resulted in a protein synthesis-dependent increase in the adhesiveness of lung tissue for peripheral blood monocytes. Adhesion of monocytes to lung tissue was not increased above baseline after 7 hours but increased more than twofold by 24 hours and persisted through 48 hours. Binding of monocyte to lung tissue was further increased when recombinant rat MCP 1 was added to monocyte suspensions immediately before being layered onto lung sections derived from either TNF alpha-treated or untreated organ cultures. Addition of antibody directed against rat CD11b/c resulted in a moderate reduction in monocyte binding. TNF or lipopolysaccharide-induced activation of mononuclear cells in the presence of [3H]leucine-labeled organ cultures resulted in lung injury as assessed by radioisotope release. Mononuclear cell-mediated organ culture injury could be partially inhibited with anti-rat MCP 1 antibody, anti-rat CD11b/c antibody, or antioxidants including catalase and deferoxamine. Anti-MCP 1 and anti-CD11b/c increased the absolute numbers of monocytes that could be retrieved from monocyte-lung co-cultures while catalase and deferoxamine did not. In vitro studies revealed that isolated rat peripheral blood monocytes produce O2- in response to MCP 1. These data provide a functional correlate for recent in vitro studies which suggest that MCP 1 may mediate leukocyte adhesive processes by up-regulating beta 2 integrin expression on monocytes. This study provides evidence that monocytes activated by MCP 1 can damage lung tissue through an oxidant-mediated mechanism. Monocyte chemoattractant protein 1 may participate in the pathogenesis of monocyte-mediated lung injury by modulating inflammatory cell adhesion as well as through monocyte activation.
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PMID:Analysis of monocyte chemoattractant protein 1-mediated lung injury using rat lung organ cultures. 810 96

SC-45662 and SC-41661A, selective arachidonate 5-lipoxygenase (5-LO) inhibitors, had markedly different effects on formyl-methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a (C5a) induced superoxide release from human neutrophils (PMNs). SC-45662 inhibited superoxide generation induced by fMLP and C5a with IC50 values of 12 and 5 microM, respectively. Furthermore, SC-45662 was capable of inhibiting fMLP and C5a induced superoxide release in PMNs primed with bacterial lipopolysaccharide, tumor necrosis factor-alpha and other priming agents. SC-41661A, a compound from the same chemical series as SC-45662, did not inhibit or induce superoxide generation, but instead primed PMNs for fMLP and C5a induced superoxide generation. The induced superoxide release was concentration dependently enhanced 2 to 4-fold at 5-50 microM. Superoxide release induced by phorbol myristate acetate or serum-activated zymosan was unaffected by either SC-45662 or SC-41661A. The regulation of superoxide generation by these compounds, both of which have the identical oxidation-reduction pharmacophore, was clearly independent of their effects on 5-LO activity. Furthermore, the mechanism by which SC-45662 and SC-41661A alter superoxide generation did not appear to depend on inhibition of xanthine oxidase, catalase or superoxide dismutase. These new compounds provide effective tools for further investigation of the relationship of these two biochemical oxidative systems.
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PMID:Contrasting effects of two arachidonate 5-lipoxygenase inhibitors on formyl-methionyl-leucyl-phenylalanine (fMLP) and complement fragment 5a induced human neutrophil superoxide generation. 814 1

Interleukin 8 (IL-8) is a recently described cytokine that functions as a potent neutrophil chemoattractant and activator. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) and the regulation of IL-8 gene expression to specifically test the hypothesis that ROI would induce production of IL-8 mRNA and protein. In lipopolysaccharide-stimulated human whole blood, the OH radical scavenger dimethyl sulfoxide (Me2SO) dramatically inhibited (approximately 90%) IL-8 production, but had minimal effects on the production of tumor necrosis factor, interleukin 1 beta (IL-1), and IL-6. To determine whether NADPH-oxidase-generated free radicals were critical in the regulation of IL-8, studies were performed using blood from patients with chronic granulomatous disease. In both normal individuals and patients with chronic granulomatous disease, production of IL-8 could be initiated with lipopolysaccharide, phytohemagglutinin, or aggregated immune complexes, and this production could be inhibited by Me2SO (1% v/v). To examine if oxidant stress represents a ubiquitous mechanism for the induction of IL-8, experiments were performed in cultured cell lines. In the human hepatoma cell line Hep-G2, Me2SO dose-dependently inhibited tumor necrosis factor-stimulated IL-8 production, with a 74 +/- 1% reduction observed at a Me2SO concentration of 1%. Direct exposure to ROI demonstrated that H2O2 stimulated IL-8 production in a dose-dependent manner in Hep-G2 cells, A549 pulmonary type II epithelial cells, and human skin fibroblasts; this induction could be prevented by addition of catalase. The production of IL-8 appeared to be specific to an oxidant stress since exposure of the cells to heat shock or chemical stress did not induce expression of IL-8. These studies demonstrate that oxidant stress is an important regulator of IL-8 gene expression and support the hypothesis that low levels of ROI may serve to initiate IL-8 production which then serves to recruit neutrophils to sites of inflammation.
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PMID:Regulation of interleukin 8 gene expression by oxidant stress. 824 94

An analysis of cell lines representing different stages of the B-cell differentiation pathway indicated that about 50% of the cell lines examined expressed exclusively wild type p53 protein. These lines therefore offer a convenient system to study the involvement of p53 in cell differentiation. When 70Z/3, a pre-B cell line which expresses wild type p53, was treated with the differentiation inducer lipopolysaccharide (LPS), it was seen that increased levels of p53 mRNA preceded specific changes in kappa (kappa) immunoglobulin expression. This increased expression of kappa specific mRNA, which was evaluated by specific PCR analysis, was blocked following transfection with mutant p53 coding plasmids. Treatment of 13A60, another cell line which endogenously expresses wild type p53, with LPS caused a secretion of IgA antibodies, also accompanied by increased p53 mRNA expression. The conclusion was that induction of B-cell differentiation involves the transcription of the p53 gene. This was further substantiated by experiments showing that differentiation of stable clones derived from the 70Z/3 cell line, harboring a p53-promoter-CAT plasmid, induced increased CAT activity. Furthermore, wild type p53 transactivated the promoter control sequences of the kappa light chain gene. Taken together, these results suggest that p53 is involved in B-cell differentiation, a pathway which involves DNA rearrangements that may be accompanied by generation of faulty DNA. The fact that wild type p53 was shown to function as a transcriptional factor, coupled with the notion that it is associated with DNA repair systems, may designate p53 as a control protein in the B-cell differentiation pathway.
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PMID:Wild type p53 functions as a control protein in the differentiation pathway of the B-cell lineage. 824 32

The purpose of this study was to determine the most potent activator of the respiratory burst of polymorphonuclear leukocytes (PMN) with respect to the oxidative modification of low density lipoprotein (LDL). Phorbol-12-myristate-13-acetate (PMA), n-formyl-methionyl-leucylphenylalanine (nFMLP), lipopolysaccharide (LPS), and opsonized zymosan (OZ) were tested. The generation of reactive oxygen species by PMN was assayed as superoxide anion production. Oxidative modification of LDL was monitored by thiobarbituric acid reactive substance (TBARS) activity, by conjugated dienes formation at 234nm and by electrophoretic mobility on agarose gel. PMA was the most potent activator of PMN, inducing a 6-fold increase in the superoxide anion production, followed by OZ (3-fold increase). PMA activation also induced the greatest modification of LDL by PMN: 700% increase of conjugated dienes formation, 222% increase of TBARS, and 70% increase in the electrophoretic mobility. The indices of oxidative modification significantly correlated with the superoxide anion generated by different activators. Also, LDL oxidation by PMN was inhibited by superoxide dismutase but not by catalase, methionine, or hydroxyl radical scavengers. Our data indicate that PMNs activated by PMA produce a mildly oxidized form of LDL by a mechanism that appears to involve the superoxide anion.
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PMID:LDL modification by activated polymorphonuclear leukocytes: a cellular model of mild oxidative stress. 829 96

Human alveolar macrophages (AM) can produce potent reactive oxygen intermediates (ROI) and arachidonic acid metabolites (eicosanoids), which have important roles in host defense and the pathogenesis of some diseases of the lung. Bacterial lipopolysaccharide (LPS) is believed to cause profound lung injury and can prime mouse peritoneal macrophages for the enhanced secretion of ROI and eicosanoids. Therefore, we investigated the effect of LPS pretreatment on the ability of AM to release superoxide anions (O2-) and leukotriene B4 (LTB4). LPS can prime AM for the enhanced secretion of O2- and LTB4, regardless of whether they are derived from nonsmokers or smokers. Moreover, judging from the time-response characteristics, this priming for LTB4 release could be inhibited in the later stages of pretreatment, when the O2(-)-releasing capacity was enhanced. The priming inhibition was prevented, at least in part, by cycloheximide, but not by SOD and/or catalase. In addition, cycloheximide also inhibited the priming for O2- release. Hence, protein synthesis might be necessary for the priming for O2- release and for inhibiting the priming for LTB4 release. This phenomenon of self-limiting the priming response with LPS seems to be very important when we consider the high oxygen tension in the lungs and the many bacterial substances inspired into alveoli.
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PMID:Lipopolysaccharide primes human alveolar macrophages for enhanced release of superoxide anion and leukotriene B4: self-limitations of the priming response with protein synthesis. 838 27


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