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)

Vascular smooth muscle cells (SMCs) are important targets for endothelium-derived nitric oxide (NO), but this production is attenuated in injured and diseased arteries and during aging. However, SMCs can produce NO themselves by expressing an inducible form of NO synthase (iNOS) under inflammatory conditions and in the repair process after arterial injury. We examined iNOS expression in SMCs derived from the aortic media of newborn, young adult, and old rats. Our results show that SMCs from newborn rats cannot produce significant amounts of NO on stimulation with interferon-gamma plus lipopolysaccharide or interleukin-1beta. In contrast, SMCs from old rats exhibit markedly enhanced iNOS activity. The difference in iNOS activity between the newborn and the old SMCs was closely correlated with levels of iNOS protein, mRNA, and gene promoter activity. Similarly, intercellular adhesion molecule-1 (ICAM-1) was also expressed more abundantly in the old than in the newborn SMCs in response to cytokines. Both iNOS and ICAM-1 are transcriptionally regulated by nuclear factor kappaB (NF-kappaB). Our data demonstrate an intense transactivation of NF-kappaB in old SMCs on tumor necrosis factor-alpha stimulation but only a weak one in newborn SMCs. The difference in the NF-kappaB activation could be explained by a much faster and more extensive IkappaBalpha degradation in old than in newborn SMCs. These data indicate that the capability to respond to proinflammatory stimuli by activating NF-kappaB differs between SMCs at different stages of development. This results in differential capability to express NF-kappaB-dependent genes such as iNOS and ICAM-1, which could have implications for host defense and the pathogenesis of vascular diseases.
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PMID:Augmented expression of inducible NO synthase in vascular smooth muscle cells during aging is associated with enhanced NF-kappaB activation. 1059 61

Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (<2 yrs), group 2 (> or =2-< or =5 yrs) and group 3 (> or =6-< or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: <2 yrs and > or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children <2 yrs expressed less human leukocyte antigen (HLA)-DR (versus > or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children <2 yrs and > or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.
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PMID:Alveolar macrophage immaturity in infants and young children. 1059 13

Mice deficient in intercellular adhesion molecule-1 (ICAM-1), lacking membranous ICAM-1, show a normal development but abnormalities of inflammatory and immune functions. Although the membrane-bound form of ICAM-1 is not detectable in the mutant strain, circulating ICAM-1 (cICAM) is present in serum from ICAM-1-deficient mice in similar amounts as in serum from wild-type mice. These findings were confirmed in vitro by flow cytometric analysis of lipopolysaccharide-stimulated spleen cells, and cICAM-enzyme-linked immunosorbent assay analysis of supernatants of cultured spleen cells. To analyze for the source of cICAM-1, spleen cell RNA was isolated and ICAM-1 RNA was amplified by reverse transcriptase-polymerase chain reaction using primers binding in the 5' and 3' untranslated regions. Different fragments were cloned and sequenced. In wild-type RNA the common 5 domain form of ICAM-1 was identified. In RNA from ICAM-1 mutant mice only 3 smaller fragments were found. Sequencing these fragments identified 3 alternatively spliced isoforms of ICAM-1, lacking 2 or 3 extracellular domains. However, in all spliced fragments the transmembrane domain was included. Therefore, we postulate that circulating forms of ICAM-1 are generated by proteolytic cleavage of membranous ICAM-1. The data indicate that the expression of membranous ICAM-1 and the appearance of circulating forms in serum are independently regulated mechanisms. (Blood. 2000;95:1350-1355)
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PMID:Circulating forms of intercellular adhesion molecule (ICAM)-1 in mice lacking membranous ICAM-1. 1066 10

We investigated the effect of cerivastatin on lipopolysaccharide (LPS)-induced intercellular adhesion molecule-1 (ICAM-1) expression in bovine aortic endothelial cells. Cerivastatin suppressed LPS-induced ICAM-1 mRNA expression. Cotreatment with geranylgeranylpyrophosphate reversed the effect of cerivastatin. Because Rho undergoes geranylgeranyl modification, we elucidated whether Rho is involved in LPS-induced ICAM-1 expression. Inhibition of Rho activity by Clostridium botulinum C3 transferase or by overexpression of RhoA T19N, a dominant-negative mutant of RhoA, decreased LPS-induced ICAM-1 expression. Although cerivastatin up-regulated endothelial nitric oxide synthase (eNOS), inhibition of nitric oxide (NO) synthesis by cotreatment with N(omega)-nitro-l-arginine methyl ester (L-NAME) exhibited no influence on the effect of cerivastatin. The present results indicate that cerivastatin prevents LPS-induced ICAM-1 expression in endothelial cells via inhibition of Rho activity. This inhibitory effect is likely unrelated to up-regulation of eNOS.
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PMID:Cerivastatin suppresses lipopolysaccharide-induced ICAM-1 expression through inhibition of Rho GTPase in BAEC. 1069 84

This study compares the signal transduction pathway which leads to the upregulation of intercellular adhesion molecule-1 (ICAM-1) expression with that of the increase in the expression of inducible nitric oxide synthase (iNOS) protein and activity caused by endotoxin in cultured J774.2 macrophages. Treatment of J774.2 cells with lipopolysaccharide E. coli (LPS) induced a concentration-dependent increase in the expression of ICAM-1 on the cell surface within 4 h and an increase in iNOS protein and activity at 24 h. The upregulation of ICAM-1 expression on J774.2 macrophages caused by LPS was significantly inhibited by pretreatment of the cells with inhibitors of the activation of the nuclear transcription factor NF-kappaB, such as L-1-tosylamido-2-phenylethylchloromethyl ketone (TPCK), pyrrolidine dithiocarbamate (PDTC), rotenone or calpain inhibitor I, but not by the tyrosine kinase inhibitors, tyrphostin AG126 or genistein. In contrast, genistein or tyrphostin AG126 also prevented the induction of iNOS protein and activity in J774.2 macrophages elicited by LPS. Thus, the increase in the expression of ICAM-1 on J774.2 macrophages by endotoxin involves the activation of NFkappaB, but not of protein tyrosine kinase.
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PMID:Upregulation of ICAM-1 expression on J774.2 macrophages by endotoxin involves activation of NF-kappaB but not protein tyrosine kinase: comparison to induction of iNOS. 1070 44

Cytokine release from inflammatory (CD14(+)) cells is reduced after repeated stimulation with lipopolysaccharide (LPS; LPS tolerance). However, it is not known whether LPS tolerance can be induced in CD14(-) cells. The aim of the present study was to determine whether endothelial cells [human umbilical vein endothelial cells (HUVEC)] could be rendered tolerant to LPS with respect to LPS-induced polymorphonuclear neutrophil (PMN) adhesion. LPS stimulation (0.5 microg/ml; 4 h) of naive HUVEC increased PMN adhesion. Pretreatment of HUVEC with LPS (0.5 microg/ml) for 24 h resulted in a reduction in the proadhesive effects of a subsequent LPS challenge. The initial LPS stimulation increased 1) mobilization of the nuclear transcription factor NF-kappaB to the nucleus and 2) surface levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selectin. In LPS-tolerant HUVEC, a second LPS challenge resulted in 1) less accumulation of NF-kappaB in the nucleus, 2) a reduction in E-selectin expression, and 3) unchanged ICAM-1 expression. LPS-tolerant cells were still capable of mobilizing NF-kappaB in response to stimulation with either interleukin-1beta or tumor necrosis factor-alpha, resulting in elevated E-selectin levels and increased PMN adhesion. These studies show for the first time that LPS tolerance can be induced in endothelial cells with respect to PMN adhesion. This tolerance is specific for LPS and is associated with an inability of LPS to mobilize NF-kappaB, resulting in less E-selectin expression.
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PMID:LPS tolerance in human endothelial cells: reduced PMN adhesion, E-selectin expression, and NF-kappaB mobilization. 1071 Mar 54

1. The effects of an unfractionated heparin preparation (Multiparin), a low molecular weight heparin preparation (Fragmin) and a selectively O-desulphated derivative of heparin lacking anticoagulant activity, have been investigated for their effects on the adhesion of human polymorphonuclear leucocytes (PMNs) to cultured human umbilical vein endothelial cells (HUVECs) in vitro. The effect of poly-L-glutamic acid, a large, polyanionic molecule was also studied. 2. Unfractionated heparin (50-1000 U ml-1), the O-desulphated derivative (0.3-6 mg ml-1) and the low molecular weight heparin (50 U-1000 U ml-1) all inhibited significantly the adhesion of 51Cr labelled PMNs to HUVECs stimulated with interleukin-1 beta (IL-1 beta; 10 U ml-1), bacterial lipopolysaccharide (LPS; 2.5 micrograms ml-1) or tumour necrosis factor-alpha (TNF-alpha; 125 U ml-1) for 6 h, whereas poly-L-glutamic acid had no effect. In addition, the three heparin preparations in the same concentration range inhibited significantly the adhesion of f-met-leu-phe-stimulated PMNs to resting HUVECs. 3. The effects of unfractionated heparin upon the expression of adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selection were also investigated, as were the effects of unfractionated heparin upon adhesion of human PMNs to previously stimulated HUVECs. Heparin had little effect upon levels of expression of these adhesion molecules on stimulated HUVECs. However, a profound effect upon PMN adhesion to previously stimulated HUVECs was demonstrated using the same preparation, suggesting that inhibition of adhesion molecule expression is not a major component of the described inhibitory effects of heparin. 4. Pre-incubation of PMNs with heparin followed by washing inhibited their adhesion to HUVECs, under different conditions of cellular activation, implying that heparin can bind to these cells and exert its anti-adhesive effects even when not directly present in the system. 5. These observations would suggest that both heparin and a low molecular weight heparin are capable of inhibiting adhesion of human PMNs to endothelial cells, an effect not dependent solely upon the polyanionic nature of these molecules, nor dependent upon their ability to act as anticoagulants.
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PMID:The effects of heparin and related molecules upon the adhesion of human polymorphonuclear leucocytes to vascular endothelium in vitro. 1071 52

The effects of two chemically unrelated nitric oxide (NO)-releasing compounds were studied on adhesion molecule expression in and neutrophil adhesion to human umbilical vein endothelial cells. Incubation of confluent monolayers of endothelial cells with increasing concentrations of lipopolysaccharide stimulated the adhesion of polymorphonuclear leukocytes to endothelial cells. Flow cytometric analysis showed that lipopolysaccharide treatment upregulated the expression of adhesion molecules E-selectin and intercellular adhesion molecule-1 (ICAM-1) in human umbilical vein endothelial cells. A novel NO-releasing compound GEA 3175 (1,2,3, 4-oxatriazolium, -3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) inhibited lipopolysaccharide-induced adhesion being more potent than the earlier known NO donor S-nitroso-N-acetylpenicillamine. The increased E-selectin expression induced by lipopolysaccharide was significantly attenuated by the two NO donors tested whereas ICAM-1 expression remained unaltered. The present data show that NO donors inhibit E-selectin expression in and neutrophil adhesion to lipopolysaccharide-stimulated vascular endothelial cells. Thus, by inhibiting leukocyte adhesion NO donors may reduce leukocyte infiltration and leukocyte-mediated tissue injury in inflammation and ischemia-reperfusion injury.
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PMID:Inhibition by nitric oxide-releasing compounds of E-selectin expression in and neutrophil adhesion to human endothelial cells. 1077 Oct 47

Infiltration of activated neutrophils into the lung appears to be a key element in the severe lung injury that develops in animal models of acute lung injury. Partial liquid ventilation with perflubron has been shown to ameliorate tissue damage compared with conventional mechanical ventilation in acute lung injury models. Pilot experiments indicated that indirect exposure to perflubron could modulate the degree to which subsequent neutrophil binding to endothelial cell monolayers was upregulated after lipopolysaccharide activation. Endothelial cell monolayers preexposed to perflubron showed >40% reductions in the surface steady-state levels of E-selectin and intercellular adhesion molecule-1 achieved after proinflammatory activation (P < 0.05), which correlated with a reduction in the real-time association constants measured by biosensor techniques. These results indicate that direct contact with the perflubron liquid phase is not necessary to attenuate inflammatory responses. Rather, diffusion of perflubron from the alveolar space into the adjacent pulmonary vascular endothelial layer may modulate neutrophil adhesion and thereby reduce the rate of infiltration of activated neutrophils into the injured lung.
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PMID:Perflubron attenuates neutrophil adhesion to activated endothelial cells in vitro. 1078 32

Classic ischemic preconditioning transiently (30 to 120 minutes) protects the myocardium against subsequent lethal ischemia/reperfusion injury. After dissipation of this acute protection, a second window of protection (SWOP) appears 12 to 24 hours later; this SWOP lasts up to 3 days. Several triggers induce a SWOP, including brief repetitive cycles of coronary artery occlusion, rapid ventricular pacing, stimulation of adenosine A(1) receptors, and administration of wall fragments of Gram-negative bacteria, such as lipopolysaccharide (LPS). The aim of this study was to investigate whether lipoteichoic acid (LTA), a cell wall fragment of Gram-positive bacteria, can induce a SWOP in a rat model of left anterior descending coronary artery (LAD) occlusion (25 minutes) and reperfusion (2 hours). Thus, 166 male Wistar rats were pretreated (2 to 24 hours) with saline, LTA (1 mg/kg IP), or LPS (1 mg/kg IP) and subjected to LAD occlusion/reperfusion. Pretreatment with LTA or LPS for 16 hours led to a substantial, approximately 65%, reduction in infarct size and a reduction in the release of cardiac troponin T into the plasma. The dose of LTA used had no toxic effect (on any of the parameters studied), whereas the same dose of LPS caused a time-dependent activation of the coagulation system and liver injury. By use of RNase protection assays, it was determined that LPS caused a time-dependent induction of tumor necrosis factor-alpha, interleukin-1beta, and manganese superoxide dismutase mRNA content in the heart, whereas LTA failed to induce manganese superoxide dismutase. LPS also caused an upregulation of the expression of intercellular adhesion molecule-1 and P-selectin, whereas LTA downregulated these molecules and attenuated the accumulation of polymorphonuclear granulocytes caused by myocardial ischemia/reperfusion. This study demonstrates for the first time that pretreatment with LTA at 8 to 24 hours before myocardial ischemia significantly reduces (1) infarct size, (2) cardiac troponin T, and (3) the histological signs of tissue injury in rats subjected to LAD occlusion and reperfusion. The mechanism(s) underlying the observed cardioprotective effects of LTA warrants further investigation but is likely to be related to its ability to inhibit the interactions between the coronary vascular endothelium and polymorphonuclear granulocytes. Therefore, LTA represents a novel and promising agent capable of enhancing myocardial tolerance to ischemia/reperfusion injury.
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PMID:Lipoteichoic acid induces delayed protection in the rat heart: A comparison with endotoxin. 1084 67

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