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)

To elucidate physiological functions of adrenomedullin (AM) secreted from vascular smooth muscle cells (VSMCs), we examined the effect of cytokines, growth factors and related substances on AM production in cultured rat VSMC. Among them, interleukin-1 alpha (IL-1 alpha), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and TNF-beta, as well as lipopolysaccharide (LPS), markedly augmented production and gene expression of AM. Although maximal stimulation levels of these substances were not greatly different, ED50 values of IL-1s (0.3 ng/ml) were about 1/10 that of TNFs and LPS. AM mRNA levels maximized at 3-6 h after stimulation with IL-1 beta and LPS, while TNF-alpha increased the AM mRNA level up to 48 h. Furthermore, IL-1 alpha, TNF-alpha and LPS additively increased AM production in VSMC. AM production was slightly augmented by fibroblast, epidermal and platelet derived growth factors. These results suggest that AM secreted from VSMC actually exerts a vasorelaxant effect under physiological conditions such as endotoxin shock, atherosclerosis and inflammation.
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PMID:Interleukin-1, tumor necrosis factor and lipopolysaccharide additively stimulate production of adrenomedullin in vascular smooth muscle cells. 785 73

A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-alpha, IL-1 alpha, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages.
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PMID:Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells. 788 14

The intercellular adhesion of circulating leukocytes to vascular endothelium is a prerequisite for leukocyte emigration from the blood to extravascular tissues. This process is facilitated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats. Both cultures contained similar numbers of cells constitutively expressing this adhesion molecule (31.4% and 29.6%, respectively). Adhesion molecule expression was up-regulated by interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were more sensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expression were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.
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PMID:Adhesion molecules on normotensive and hypertensive rat brain endothelial cells. 790 12

The adherence of monocytes to the endothelium is an early event in atherogenesis. Our previous studies have demonstrated that oxidized LDL induced U937 cells-endothelial interactions and that HDL prevented oxidized LDL effects. Here, we provide evidence that treatment of endothelial cells with the anti-inflammatory agent indomethacin abolished oxidized LDL as well as interleukin 1- and lipopolysaccharide-stimulated U937 adhesion. It is noteworthy that HDL, which is known to be protective against atherosclerosis, was effective only in negating U937 adhesion induced by oxidized LDL, while it did not affect interleukin 1- and lipopolysaccharide-induced hyperadhesiveness in endothelial cells. Since indomethacin inhibits cyclooxygenase which is the key enzyme in the synthesis of prostanoids, we have studied the effect of oxidized LDL on the expression of cyclooxygenase type 2 and demonstrated that oxidized LDL induces a sustained increase in the expression of cyclooxygenase mRNA.
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PMID:Modulators of oxidized LDL-induced hyperadhesiveness in human endothelial cells. 798 May 28

Macrophage scavenger receptors exhibit unusually broad binding specificity for polyanionic ligands and have been implicated in atherosclerosis and various host defense functions. Using a radiolabeled, secreted form of the type I bovine macrophage scavenger receptor in an in vitro binding assay, we have found that this receptor binds to intact Gram-positive bacteria, including Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus aureus, Enterococcus hirae, and Listeria monocytogenes. Competition binding studies using purified lipoteichoic acid, an anionic polymer expressed on the surface of most Gram-positive bacteria, show that lipoteichoic acids are scavenger receptor ligands and probably mediate binding of the receptor to Gram-positive bacteria. Lipoteichoic acids, for which no host cell receptors have previously been identified, are implicated in the pathogenesis of septic shock due to Gram-positive bacteria. Scavenger receptors may participate in host defense by clearing lipoteichoic acid and/or intact bacteria from tissues and the circulation during Gram-positive sepsis. Since scavenger receptors have been previously shown to bind to and facilitate bloodstream clearance of Gram-negative bacterial endotoxin (lipopolysaccharide), these receptors may provide a general mechanism for macrophage recognition and internalization of pathogens and their cell surface components.
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PMID:The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid. 812 96

Oxidized low-density lipoprotein (oxLDL) has been characterized as an atherogenic molecule responsible for the induction of a variety of gene products. One such gene, tissue factor (TF), the cellular initiator of the coagulation cascade, is not expressed in normal vascular tissue but is expressed by monocytes and foam cells in atherosclerotic lesions. Therefore, we examined the effect of oxLDL on TF expression in cultured human adherent monocytes. Endotoxin-free oxLDL alone did not induce TF expression in adherent monocytes. However, oxLDL significantly enhanced TF expression induced by the inflammatory mediator, bacterial lipopolysaccharide (LPS), in a time- and dose-dependent manner. In contrast, oxLDL did not alter LPS-mediated production of interleukin-8 and actually inhibited LPS-induced secretion of tumor necrosis factor-alpha, suggesting that some aspects of the signaling pathways for TF induction differ from those of other LPS-responsive monocyte/macrophage gene products. Thus, this study documents specific modulation of the expression of LPS-inducible genes in monocytic cells by oxLDL. Factors that enhance TF expression in monocyte/macrophage cells present in atheroma may contribute to the severity of thrombotic episodes and complications observed in atherosclerosis.
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PMID:Oxidized LDL enhances lipopolysaccharide-induced tissue factor expression in human adherent monocytes. 817 55

Monokines, such as interleukin-1, have been implicated in the pathogenesis of several pathologic processes, including the initiation and progression of atherosclerosis. Since estrogen has been identified as a modulator of atherosclerosis progression, we sought to examine the effect of estrogen on the inducible expression of interleukin-1 beta (IL-1 beta) and interleukin-1 alpha (IL-1 alpha) mRNA in the monocytic cell line, THP-1. Cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) (50 ng/ml) for 48 or 96 h to induce differentiation. Some cells were treated with lipopolysaccharide (LPS) (10 micrograms/ml) in the last 3 h and/or 10(-9) M ethinyl estradiol (estrogen) in the last 20 h. Total cellular RNA was isolated, and cDNA was synthesized and amplified using the polymerase chain reaction (PCR) using two sets (pairs) of 32P-labeled primers, one for IL-1 beta (product size 388 bp) and the second for the internal control, beta-actin (1126 bp), or to detect another cytokine mRNA, a set of primers for IL-1 alpha (product size 420 bp) and beta-actin. The PCR products were separated on a 3.0% agarose gel and the ratio of radioactivity incorporated into cytokine PCR products and beta-actin products was determined to assess the relative changes in the relative levels of cytokine to beta-actin mRNA abundance in response to various inducers. Treatment with TPA for 48 h induced expression of IL-1 beta mRNA, an effect that was enhanced two fold by LPS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The inducible expression of THP-1 cell interleukin-1 mRNA: effects of estrogen on differential response to phorbol ester and lipopolysaccharide. 818 19

Tissue factor (TF) is the predominant physiological initiator of coagulation, and its regulation is a critical aspect of endothelial cell hemostatic function. This report describes the regulation of TF mRNA expression by two physiological agonists: minimally oxidized low-density lipoprotein (MM-LDL), which may modulate endothelial hemostatic function in atherosclerosis, and lipopolysaccharide (LPS), which is a mediator of septic shock. Northern blot analysis of total RNA from human endothelial cells exposed to either MM-LDL or LPS for varying times showed that TF mRNA increased sharply at 1 hour, peaked at 2 to 3 hours, and declined to basal levels by 6 to 8 hours after treatment. The half-life of TF mRNA in MM-LDL- and LPS-exposed endothelial cells was approximately 45 minutes and 40 minutes, respectively. The rate of TF mRNA degradation was similar at 1 and 4 hours after exposure in either MM-LDL- or LPS-stimulated endothelial cells. Nuclear runoff transcription assays showed a significantly increased rate of TF gene transcription in both MM-LDL- and LPS-exposed endothelial cells. Cycloheximide inhibited the induction of TF protein activity, but it enhanced the accumulation of TF mRNA in MM-LDL- and LPS-induced endothelial cells. These results indicated that regulation of TF expression by MM-LDL and LPS in human endothelial cells occurs principally at the level of gene transcription.
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PMID:Regulation of endothelial cell tissue factor expression by minimally oxidized LDL and lipopolysaccharide. 821 12

We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from the porcine brain, is produced by endothelial cells and proposed that CNP can exert local control over vascular tone and growth as a local regulator from endothelial cells. Since cytokines play pivotal roles in the control of vascular tone and structure, we have examined effects of various cytokines on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP. While interleukin (IL)-2 had no significant effect on CNP secretion, IL-1 alpha, IL-1 beta and tumor necrosis factor (TNF)-alpha stimulated CNP secretion in a time- and dose-dependent manner. Among them, TNF-alpha, one of the key mediators for inflammation and vascular remodeling, induced more than two orders of magnitude increase in CNP secretion. In addition, lipopolysaccharide (LPS) potently stimulated CNP secretion. These results indicate that IL-1, TNF-alpha and LPS, the endotoxin itself, can regulate local vascular tone and growth through the activation of CNP secretion from endothelial cells. Therefore, CNP could be of clinical relevance as an autocrine/paracrine regulator from endothelial cells for systemic and local cytokine-associated disorders, such as endotoxin shock and atherosclerosis.
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PMID:Cytokine-induced C-type natriuretic peptide (CNP) secretion from vascular endothelial cells--evidence for CNP as a novel autocrine/paracrine regulator from endothelial cells. 824 33

Lysophosphatidylcholine is increased in the plasma of hypercholesterolemic patients, is a component of oxidatively modified low-density lipoprotein, and, as such, may play an important role in atherosclerosis. Here we demonstrate that in human monocytes, lysophosphatidylcholine increases the level of mRNA encoding the heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle mitogen. Lysophosphatidylcholine treatment also enhances the release of heparin-binding mitogenic activity by these cells in culture. The anti-inflammatory glucocorticoid dexamethasone inhibits the upregulation of HB-EGF mRNA induced by either lysophosphatidylcholine or bacterial lipopolysaccharide in cultured monocytes. However, the responses induced by lysophosphatidylcholine and by lipopolysaccharide differ in their kinetics. In addition, the response to lysophosphatidylcholine is resistant to the action of cycloheximide, whereas the response to lipopolysaccharide is not, suggesting that the activation mechanisms induced by these two stimuli are different. Since a nuclear run-on assay showed no effect of lysophosphatidylcholine on the transcription of the HB-EGF gene, we speculate that lysophosphatidylcholine may increase the level of HB-EGF mRNA by altering the processing or degradation of primary or mature transcripts. Lysophosphatidylcholine enhancement of monocyte production of HB-EGF may represent an important result of the interactions among oxidized low-density lipoprotein and monocyte-derived macrophages and may play a role in initiation of smooth muscle proliferation in atherogenesis.
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PMID:Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes. 830 33


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