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 aim of this study was to assay the influence of capsular polysaccharide (CPS), lipopolysaccharide (LPS) and components of B. thetaiotaomicron lipopolysaccharide--polysaccharide part (PS) and lipid part (lipid A) on the expression of adhesion molecules associated with inflammation (ICAM-1, VCAM-1, E-selectin) on the surface of vascular endothelial cells. Capsular polysaccharide was isolated by the method of Poxton and Ip (1981). Lipopolysaccharides were extracted using the hot phenol-water method (Westphal and Jann, 1965). Components of LPS were prepared by mild acid hydrolysis of lipopolysaccharide. Experiments with bacterial compounds at concentrations 10, 1, 0.1 and 0.01 (mg/ml) were performed on HMEC-1 cell line (human dermal microvascular endothelial cells). Immunoenzymatic ELISA test with mouse monoclonal antibodies against human: ICAM-1, VCAM-1 and E-selectin was applied to determine adhesion molecules. Resting HMEC-1 and E. coli O55:B5 LPS were used as controls in each experiment. Lipopolysaccharides were the strongest stimulants of endothelial adhesion molecules. Capsular polysaccharide caused the expression of three adhesion molecules, but only at the highest concentration (10 mg/ml). The stimulatory activities of LPS lipid components were much higher than the activities of polysaccharide parts. PS preparations did not reveal the property of adhesion molecule stimulation or their activities were weak. The activity of B. thetaiotaomicron cell-surface antigens in the process of adhesion molecule stimulation on vascular endothelium was lower than the activity of E. coli LPS.
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PMID:[Stimulation of adhesion molecules on vascular endothelium by capsular polysaccharide, lipopolysaccharide and components of lipopolysaccharide from Bacteroides thetaiotaomicron]. 1114 69

Transcription factor activating transcription factor (ATF)-2 is activated by inflammatory signals transduced by the JNK and p38 MAP kinase pathways. To better define the role of ATF-2 in inflammation, adult mice expressing small amounts of a mutant ATF-2 protein were challenged with lipopolysaccharide (LPS), anti-CD3 antibody or virus. Within 3 h of challenge by LPS, ATF-2 mutant mice had decreased induction of the adhesion molecules E-selectin, P-selectin and VCAM-1 as well as the cytokines tumor necrosis factor-alpha, IL-1beta and IL-6 compared with control mice. Stimulation of T lymphocytes by anti-CD3 antibody also showed less induction of IL-1 and IL-6 in ATF-2 mutant tissues. ATF-2 mutant thymocytes treated with anti-CD3 antibody in vitro demonstrated reduced induction of c-Jun, JunB, JunD and Fra-2. However, similar to what was observed after p38 kinase inhibition in normal mice, relative ATF-2 deficiency did not prevent the development of a mononuclear cell infiltrate in the week following an inflammatory stimulus. ATF-2 mutant mice proved more susceptible to death than control mice from LPS plus D-galactosamine injection or Coxsackievirus B3 infection and had a higher incidence of mononuclear pulmonary infiltrates after exposure to Herpes simplex virus-1. ATF-2 is essential for maximal immediate induction of adhesion molecules and cytokine genes, but at later time points may even protect against overactive immune responses.
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PMID:Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice. 1115 57

One of the recognized associations of bacterial infection with cardiovascular events is the activation of endothelium and upregulation of adhesion molecules. The two major proinflammatory mediators implicated in the causation of cardiovascular events, bacterial lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF), were found to cooperate to enhance the adhesive properties of endothelial cells. These caused synergistic upregulation of intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 in human umbilical vein endothelial cells as determined by flow cytometry analysis and enzyme-linked immunosorbent assay. This synergism was not due to TNF causing an upregulation of CD14 expression. Treatment with both LPS and TNF resulted in a marked increase in the translocation of NF-kappaB into the nucleus. The activity of p38 mitogen-activated protein kinase was also synergistically enhanced, while the activity of c-jun N-terminal kinase was increased in an additive manner. The results demonstrate that LPS and TNF act synergistically to upregulate the expression of endothelial cell adhesion molecules, possibly by amplification of signaling pathways upstream of transcription. These findings have implications for the understanding of the acceleration of atherosclerotic events seen in low-grade infections with gram-negative organisms.
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PMID:Bacterial lipopolysaccharide and tumor necrosis factor alpha synergistically increase expression of human endothelial adhesion molecules through activation of NF-kappaB and p38 mitogen-activated protein kinase signaling pathways. 1117 88

To disclose cell-to-cell interaction associated with the defensive mechanism of the peritoneum, the peritoneum was stimulated with lipopolysaccharide (LPS) and analyzed three-dimensionally, ultrastructurally, and immunohistochemically with immunoSEM (scanning electron microscopy). The activated hepatic peritoneal surface demonstrated numerous microvilli with the adhesion molecules ICAM-1 and VCAM-1. They were restricted to villi and peaked at 1.5 microg/g body weight of LPS. Delicate strands appeared moderately and were interwoven among microvilli with increasing LPS. These strands did not express ICAM-1 or VCAM-1, but fibronectin. Leukocytes began to adhere to the peritoneal surface above die value of LPS (2.5 microg). These results suggest that the peritoneal surface gives a defensive sheet for cell-to-cell interaction through adhesion molecules and fibronectin.
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PMID:Expression of adhesion molecules and fibronectin of activated peritoneal surface with lipopolysaccharide (LPS) analyzed with immuno SEM. 1150 61

We used cDNA arrays to investigate differentially expressed genes in astrocytes challenged with lipopolysaccharide (LPS). Astrocyte cultures were prepared from 1-day-old rat brains. Purified astrocytes were treated with LPS (1 microg/ml) for 2, 8 and 48 h. Differentially expressed genes in these astrocytes were examined with Atlas rat cDNA arrays. At all the three time points studied, three genes were found consistently up-regulated: I-kappaB alpha chain, NF-kappaB, and interferon induced protein. In addition to these three, six other genes were also up-regulated at 2 and 8 h. They were genes encoding vascular cell adhesion protein 1 (VCAM-1), interferon regulatory factor 1 (IRF-1), mitochondrial hydroxymethylglutaryl-CoA synthase (HMG-CoA synthase), aldehyde dehydrogenase 2, macrophage inflammatory protein 1 (MIP-1) and neurotensin receptor 2. At these two time points, three genes were down-regulated: copper-zinc-containing superoxide dismutase 1 (SOD-1), insulin-like growth factor binding protein 1 (IGFBP-1), and insulin-like growth factor binding protein 3 (IGFBP-3). Expression of several differentially expressed genes in cDNA array (I-kappaB, VCAM-1 and MIP-3) were further confirmed by reverse transcription polymerase chain reaction study. The prominently modulated genes could be classified into three categories: nuclear transcription factors, pro-inflammatory cytokines/chemokines and metabolic enzymes. Application of pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kB (NF-kappaB), prior to LPS stimulation not only prevented up-regulation of NF-kappaB gene expression, but also completely blocked up-regulation of pro-inflammatory cytokine genes (TNF-alpha and interleukin-1beta) and two chemokine genes: CXC chemokine LIX and CC chemokine MIP-3 alpha. These results indicate that both up-regulation of inflammatory cytokine expression and down-regulation of growth factor expression are probably involved in the response of astrocytes upon exposure to LPS.
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PMID:Analysis of genes differentially expressed in astrocytes stimulated with lipopolysaccharide using cDNA arrays. 1157 93

It is well established that constitutive production of nitric oxide is central to numerous processes in the microvasculature, including controlling the trafficking of inflammatory leucocytes. However, during many inflammatory responses induction of inducible nitric oxide synthase (iNOS) increases nitric oxide production. The role of iNOS-derived nitric oxide in modulating leucocyte recruitment is less well understood, although recent studies using iNOS-deficient mice have begun to examine this issue. This article describes much of the work that implicates iNOS as having a role in controlling leucocyte recruitment, including the intravital microscopy studies which revealed that iNOS-deficient mice have elevated leucocyte-endothelial cell interactions during endotoxaemia. Furthermore in additional studies, we compared expression of endothelial adhesion molecules in wild-type and iNOS-deficient mice, under conditions in which iNOS was expressed. Adhesion molecule expression was measured using an in vivo dual radiolabel immunoassay. To induce iNOS, mice were treated with either 1 or 50 microg of bacterial lipopolysaccharide (LPS), and 4 h later expression of P-selectin, E-selectin and vascular cell adhesion molecule-1 was determined in eight different tissues. In nearly all cases, adhesion molecule expression did not differ between the two types of mice, either in the absence of an inflammatory stimulus, or following LPS treatment. These findings indicate that iNOS does not regulate expression of endothelial adhesion molecules either under basal conditions, or during the endotoxaemic response. This further suggests that alterations in leucocyte function may mediate the modulating effect of iNOS on leucocyte recruitment.
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PMID:Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice. 1167 34

Thioredoxin (Trx), a redox enzyme with a conserved active site (Cys-32-Gly-Pro-Cys-35), is induced and secreted into circulation in response to inflammation. Studies here demonstrate that elevating Trx levels in circulation either by i.v. injection of recombinant Trx or stimulating Trx release in Trx-transgenic mice dramatically blocks lipopolysaccharide (LPS)-stimulated neutrophil migration in the murine air pouch chemotaxis model. Furthermore, we show that leukocyte recruitment induced by the murine chemokines KC/GROalpha, RANTES (regulated upon activation, normal T cell expressed and secreted), and monocyte chemoattractant protein-1 (MCP-1) is suppressed also in Trx-transgenic mice. Addressing the mechanism responsible for this suppression, we show that circulating Trx blocks (i) the LPS-stimulated in vitro activation of neutrophil p38 mitogen-activated protein kinase, (ii) the normal down-regulation of CD62L on neutrophils migrating into the LPS-stimulated air pouch, and (iii) the in vitro adhesion of LPS-activated neutrophils on endothelial cells. However, as we also show, Trx does not alter the expression of endothelial cell adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, CD62P, and CD62E) within 3 h. Collectively, these findings indicate that elevated levels of circulating Trx interfere with chemotaxis by acting directly on neutrophils. We discuss these findings in the context of recent studies reporting beneficial effects of acutely elevated Trx in ischemic injury and negative effects associated with chronically elevated Trx in HIV disease.
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PMID:Circulating thioredoxin suppresses lipopolysaccharide-induced neutrophil chemotaxis. 1174 67

The influence of metronidazole on the level of expression of adhesion molecules ICAM-1, VCAM-1 and E-selectin on the surface of vascular endothelial cells activated with B. fragilis endotoxins and enterotoxin was examined. Three enterotoxigenic (ETBF) strains and one nonenterotoxigenic (NTBF) strain were used for lipopolysaccharide extraction. Enterotoxin was prepared from the culture supernatant of the reference B. fragilis ATCC 43858 strain. Expression of adhesion molecules on vascular endothelial cells (HMEC-1 cell line) was determined after their stimulation with bacterial compounds at the concentration of 10 micrograms/ml in the presence of metronidazole at the concentration of 4 micrograms/ml. Endothelial cells were activated for 4 hours (E-selectin expression) and for 24 hours (ICAM-1 and VCAM-1 expression). Adhesion molecules were detected in immunoenzymatic test (ELISA) with mouse, monoclonal antibodies against human ICAM-1, VCAM-1 and E-selectin. The results of experiments suggest, that metronidazole enhances the expression of examined adhesion molecules on endothelial cells. This antimicrobial agent causes some changes in the expression of endothelial ICAM-1, VCAM-1 and E-selectin stimulated by B. fragilis endotoxins and enterotoxin.
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PMID:[The effect of metronidazole on stimulation of adhesion molecule expression on the surface of vascular endothelial cells by Bacteroides fragilis endotoxins and enterotoxin]. 1175 5

The adhesive interactions involved in monocyte recruitment to the alveolar space in vivo are only poorly defined. To study these interactions, we used a recently developed mouse model that allowed the separation and quantification of freshly recruited monocytes, resident alveolar macrophages (rAM), neutrophils, and lymphocytes in the bronchoalveolar compartment by fluorescence activated cell sorting technology. In these mice, the combined intratracheal administration of the monocyte chemoattractant JE/monocyte chemotactic protein (MCP)-1 and low dose Escherichia coli lipopolysaccharide (LPS) induces a self-limiting pulmonary inflammatory response, characterized by well-controlled sequelae of both neutrophil and monocyte emigration into the alveolar space. In contrast, challenge with JE/MCP-1 provokes the emigration only of monocytes in the absence of lung inflammation. Using an array of function-blocking monoclonal antibodies (mAb) (anti-CD11a, -CD11b, -CD18, -CD49d, -CD54, and -CD106), we characterized the adhesive interactions underlying the transendothelial and transepithelial leukocyte traffic in intact animals. Alveolar monocyte recruitment elicited by JE/MCP-1 alone was strictly dependent on CD11b/CD18, CD54, and CD49d, and partly dependent on CD11a, but not dependent on CD106. In response to JE/MCP-1 plus E. coli LPS, we observed additional engagement of CD11a and CD106 for enhanced alveolar monocyte transmigration. Comigrating neutrophils were found to primarily utilize CD11b, CD18, and CD54, but not CD49d, CD106, or, surprisingly, CD11a. This contrasted with the effect of CD11a on alveolar challenge with macrophage inflammatory protein (MIP)-1alpha instead of JE/MCP-1. In conclusion, we found that in an intact mouse model allowing detailed phenotyping of leukocyte traffic into the alveolar space, the molecular pathways involved in JE/MCP-1-driven monocyte efflux differed under noninflammatory and inflammatory (presence of LPS) conditions. Moreover, the profile of adhesive interactions underlying the monocyte efflux differed from that characterizing neutrophil trafficking.
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PMID:Molecular pathways of monocyte emigration into the alveolar air space of intact mice. 1177 37

Greatly increasing the amounts of flaxseed oil [rich in alpha-linolenic acid (ALNA)] or fish oil (FO); [rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in the diet can decrease inflammatory cell functions and so might impair host defense. The objective of this study was to determine the effect of dietary supplementation with moderate levels of ALNA, gamma-linolenic acid (GLA), arachidonic acid (ARA), DHA, or FO on inflammatory cell numbers and functions and on circulating levels of soluble adhesion molecules. Healthy subjects aged 55 to 75 yr consumed nine capsules per day for 12 wk. The capsules contained placebo oil (an 80:20 mix of palm and sunflowerseed oils) or blends of placebo oil with oils rich in ALNA, GLA, ARA, or DHA or FO. Subjects in these groups consumed 2 g ALNA; approximately 700 mg GLA, ARA, or DHA; or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily from the capsules. Total fat intake from the capsules was 4 g per day. None of the treatments affected inflammatory cell numbers in the bloodstream; neutrophil and monocyte phagocytosis or respiratory burst in response to E. coli; production of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in response to bacterial lipopolysaccharide; or plasma concentrations of soluble intercellular adhesion molecule-1. In contrast, the ALNA and FO treatments decreased the plasma concentrations of soluble vascular cell adhesion molecule-1 (16 and 28% decrease, respectively) and soluble E-selectin (23 and 17% decrease, respectively). It is concluded that, in contrast to previous reports using higher amounts of these fatty acids, a moderate increase in consumption of long-chain n-6 or n-3 polyunsaturated fatty acids does not significantly affect inflammatory cell numbers or neutrophil and monocyte responses in humans and so would not be expected to cause immune impairment. Furthermore, we conclude that moderate levels of ALNA and FO, which could be incorporated into the diet, can decrease some markers of endothelial activation and that this mechanism of action may contribute to the reported health benefits of n-3 fatty acids.
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PMID:Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. 1179 50


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