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)

Human 22K factor is a cytokine released by mitogen-stimulated peripheral blood leukocytes. The factor stimulates fibroblasts to produce interferon-beta (IFN-beta) and thereby exerts antiviral activity on these cells. It was identified as interleukin-1 beta (IL-1 beta) by its amino-acid sequence and spectrum of biological activities. The pyrogenic and haematological effects of pure 22K factor were studied at different doses and were compared with those of endotoxin and interferon. 22K factor dose-dependently induced fever in rabbits, 0.1 microgram/kg being a minimum effective dose. Intravenous injection in rabbits caused immediate granulocytosis at low dose, while a profound granulopenia followed by hypergranulocytosis was observed at high dose. Preparations of pure 22K factor were free of detectable lipopolysaccharide and lost their biological effects after heat-treatment. Repeated injections of 22K factor did not result in a state of tolerance. There is no evidence that the effects in vivo of 22K factor were mediated by induction of interferon. Human 22K factor, a weak and species-specific inducer in IFN-beta in vitro, did not induce detectable amounts of circulating interferon in rabbits. Moreover, injection of rabbits with IFN-beta resulted in a weak effect on body temperature and granulocyte counts as compared to similar doses of 22K factor.
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PMID:Pyrogenic and haematological effects of the interferon-inducing 22K factor (interleukin 1 beta) from human leukocytes. 349 97

The role of endogenous tumor necrosis factor alpha (TNF-alpha) and interferon-beta (IFN-beta) in lipopolysaccharide (LPS)-induced activation of the inducible nitric-oxide synthase (i-NOS) gene was investigated. By Northern analysis or reverse-transcription polymerase chain reaction, the mouse macrophage cell line (J774) was found to respond to LPS treatment by increased expression of mRNAs specific for TNF-alpha, IFN-beta, and i-NOS with the kinetics unique for each gene. Bioassay of the culture supernatants showed that TNF-alpha and IFN-beta secreted by J774 cells increased from an undetectable level to about 300 and 340 units/ml, respectively, 3-6 h after LPS stimulation. Nitrite concentration was found to increase from 0 to 7.8 and 28.5 microM by 12 and 24 h, respectively, in the culture supernatant of LPS-treated J774 cells. The presence of a neutralizing dose of antibodies against IFN-beta, but not against TNF-alpha, during treatment with either 10 ng or 1 microgram of LPS/ml significantly, but not completely decreased the level of i-NOS-specific mRNA expression and NO production. The incubation of J774 cells with mouse natural IFN-beta itself (up to the level of 1,200 units/ml) did not induce i-NOS-specific mRNA and therefore did not stimulate J774 cells to produce NO. However, natural IFN-beta synergistically augmented the expression of i-NOS mRNA and the production of NO by J774 cells triggered by suboptimal concentrations of LPS (1 to 5 ng/ml). These data thus suggest that endogenous IFN-beta, but not TNF-alpha, produced by LPS-stimulated J774 cells specifically contributes, probably in an auto/paracrine fashion, to the activation of the i-NOS gene expression by LPS.
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PMID:Role of endogenous interferon-beta in lipopolysaccharide-triggered activation of the inducible nitric-oxide synthase gene in a mouse macrophage cell line, J774. 751 94

The tryptophan decyclizing enzyme indoleamine 2,3-dioxygenase (IDO) was induced in human monocyte-derived macrophages (MDM) treated with human recombinant interferon-beta (IFN-beta) or interferon-gamma (IFN-gamma). Treated cells exhibited dose-dependent increases in IDO when assayed 48 hr after treatment. Cells exposed to IFN-gamma were observed to exhibit consistently higher peak levels of IDO when compared with cells incubated in the presence of IFN-beta. When IFN-beta-treated cells were incubated in the presence of specified amounts of bacterial lipopolysaccharide (LPS) or liposome-encapsulated muramyl tripeptide (MTP), peak IDO activity increased such that enzyme activity was comparable to maximal activity observed with IFN-gamma-treated cells. LPS and MTP also upregulated IFN-gamma-mediated IDO activity when suboptimal amounts of IFN-gamma were used. When macrophages were costimulated with various concentrations of human recombinant interleukin 1 alpha (IL-1 alpha), along with either maximum-stimulating amounts of IFN-beta or suboptimal amounts of IFN-gamma, IDO activity was upregulated in a manner similar to results obtained using the microbial products as stimuli. While neither IL-1 alpha or IL-1 beta was detected in culture supernatants from macrophages treated with either LPS or MTP (alone or in combination with IFN), IL-1 alpha was detected in cell lysates of macrophages treated with these upregulators. Although neutralizing antibody to IL-1 alpha abolished the upregulatory effect of exogenous IL-1 alpha, it had no effect on upregulation by LPS or MTP. This suggests that although LPS and MTP may induce production of cell-associated IL-1 alpha, upregulation of IDO activity by these agents is independent of IL-1 alpha production and may be mediated through distinct pathways.
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PMID:Upregulation of interferon-induced indoleamine 2,3-dioxygenase in human macrophage cultures by lipopolysaccharide, muramyl tripeptide, and interleukin-1. 772 88

Interleukin (IL)-8 mRNA expression was investigated in human dental pulp fibroblast cultures after stimulation with lipopolysaccharide (LPS) prepared from Prevotella intermedia and inflammatory cytokines. The expression of IL-8 mRNA and the release of IL-8 induced by P. intermedia LPS in pulpal fibroblast cultures were detected by Northern blot analysis and ELISA, respectively. The sufficient concentration of P. intermedia LPS on the IL-8 mRNA expression was 0.1 microgram/ml in pulpal fibroblast cultures. IL-8 mRNA levels began to increase after 2 h of exposure, reached a maximum at 4 to 8 h, and declined after 48 h, reaching the unstimulated level by 60 h. IL-8 production by the pulpal fibroblasts began to increase after 8 h of exposure upon stimulation with 10 microgram/ml of P. intermedia LPS. By contrast Salmonella LPS and synthetic lipid A did not increase IL-8 mRNA concentrations in pulpal fibroblast cultures. Recombinant human IL-1 alpha, beta, and tumor necrosis factor-alpha were capable of stimulating these cells to express IL-8 mRNA but natural human interferon-beta, gamma, and recombinant human IL-6 were incapable in our assay. These results suggest that pulpal fibroblasts are immunoresponsive cells and can elaborate IL-8 upon stimulation with P. intermedia LPS.
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PMID:Interleukin-8 gene expression by human dental pulp fibroblast in cultures stimulated with Prevotella intermedia lipopolysaccharide. 861 87

We previously reported that in vitro culture of human peripheral blood monocytes resulted in a time-dependent differentiation into macrophages and in an enhanced capacity for producing certain cytokines [i.e., tumor necrosis factor alpha, interleukin-6 (IL-6), and interferon-beta (IFN-beta)] in response to bacterial lipopolysaccharide (LPS). HIV-1 infection or gp120 treatment of monocyte/macrophages resulted in the induction of low levels of IFN-beta, which were very effective in restricting viral replication in 7-day cultured macrophages but not in freshly isolated cells. This enhanced response of macrophages was due to a higher sensitivity of these cells to the antiviral effect of IFN-beta. Consistent with this finding, 7-day cultured macrophages exhibited higher levels of type I IFN receptors than 1-day cultured monocytes. Treatment of monocyte/macrophages with gp120 also caused a marked increase in IL-10 secretion, regardless of the differentiation state. No IL-12 secretion was detected in monocyte/macrophage cultures treated with gp120 alone. However, consistent IL-12 secretion was found in 7-day cultured macrophages primed with IFN-beta and subsequently stimulated with gp120. Macrophages responded more efficiently than monocytes to the priming effect of IFN-beta for IL-12 production. This was consistent with a stronger antiviral response against vesicular stomatitis virus by these cells as well as with a higher expression of IFN-beta receptors. The finding that the acquisition of the macrophage phenotype is associated with an increased capacity to respond to environmental signals (such as type I and type II IFNs) underlines the importance of the differentiation process for the selection of a certain repertoire of responses that may allow these cells to have important functions in vivo.
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PMID:Induction of cytokines by HIV-1 and its gp120 protein in human peripheral blood monocyte/macrophages and modulation of cytokine response during differentiation. 922 92

We studied the pathways of macrophage response to lipopolysaccharide (LPS). When mouse macrophages pre-exposed to LPS were restimulated with this agent, reduced tumour necrosis factor-alpha (TNF-alpha) responses (desensitization/endotoxin tolerance) were accompanied by increased (priming) nitric oxide (NO) responses. Priming was also inducible with recombinant interferon-beta (IFN-beta). The requirement of TNF-alpha biosynthesis in the LPS-induced priming was also suggested by the observation that both anti-TNF-alpha serum and pentoxifylline inhibited this effect. However, addition of mouse recombinant TNF-alpha (mrTNF-alpha) did not enhance the priming induced by LPS or IFN-beta, and preincubation with mrTNF-alpha alone, or in association with other cytokines produced by macrophages (interleukin-1 beta, interleukin-6, or leukaemia inhibitory factor), did not induce a priming effect. We found however, that pentoxifylline, which blocked the priming, also decreased the level of membrane-bound TNF-alpha. Furthermore, exposure to compound BB-3103 (a metalloproteinase inhibitor that blocks the processing of membrane-bound TNF-alpha yielding to the secreted cytokine) enhanced the priming effect, the expression of membrane TNF-alpha and the specific binding of LPS. These observations suggest that the membrane form of TNF-alpha is involved in the interaction of LPS with a receptor required for LPS-induced priming.
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PMID:Involvement of the membrane form of tumour necrosis factor-alpha in lipopolysaccharide-induced priming of mouse peritoneal macrophages for enhanced nitric oxide response to lipopolysaccharide. 941 35

Excessive nitric oxide/peroxynitrite generation has been implicated in the pathogenesis of multiple sclerosis, and the demonstration of increased astrocytic nitric oxide synthase activity in the postmortem brain of multiple sclerosis patients supports this hypothesis. Interferon-beta is used for the treatment of multiple sclerosis, but currently little is known regarding its mode of action. Exposure of astrocytes in culture to interferon-gamma plus lipopolysaccharide results in stimulation of nitric oxide release. Using a coculture system, we have been able to use astrocytes as a source of nitric oxide/peroxynitrite in an attempt to "model" the effects of raised cytokine levels observed in multiple sclerosis and to monitor the effect on neurones. Our results indicate that stimulation of astrocytic nitric oxide synthase activity causes significant damage to the mitochondrial activities of complexes II/III and IV of neighbouring neurones. This damage was prevented by a nitric oxide synthase inhibitor, suggesting that the damage was nitric oxide-mediated. Furthermore, interferon-alpha/beta also prevented this damage. In view of these results, we suggest that a possible mechanism of action of interferon-beta in the treatment of multiple sclerosis is that it prevents astrocytic nitric oxide production, thereby limiting damage to neighbouring cells, such as neurones.
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PMID:Pretreatment of astrocytes with interferon-alpha/beta prevents neuronal mitochondrial respiratory chain damage. 942 92

In vitro production of tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and oligoclonal IgG (IgG OB) was evaluated in the aim to investigate their profile in correlation with multiple sclerosis (MS) clinical activity and clinical course. Whole blood stimulation with lipopolysaccharide or concanavalin A was performed in 61 patients presenting with relapsing-remitting, relapsing-progressive or chronic progressive MS; treatments received were: none, azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon-beta 1a (IFN-beta 1a) and corticosteroids (CST). The cinetics of cytokine production showed that (i) in the absence of treatment, TNF-alpha and IL-6 dropped respectively after and during the periods surrounding relapse, while IL-4 was increasing before and IL-10 after relapse; (ii) with AZA, TNF-alpha and IL-6 lowered before exacerbation, IL-4 prolonged high levels after and IL-10 before relapse; (iii) with IFN-beta 1a, IL-10 was already increasing before relapse, and TNF-alpha was higher after relapse. When cytokine levels were analysed independently from MS clinical activity, the use of AZA inhibited IgG OB and TNF-alpha synthesis (P = 0.002) but increased IL-4 (P = 0.0024), whereas IFN-beta 1a stimulated TNF-alpha and inhibited IgG OB and IL-4 production. CST inhibited TNF-alpha, IL-6, IL-4 and IgG OB synthesis. This study stresses both the weight of clinical parameters and of methodology used in results obtained in cytokine analysis in MS.
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PMID:In vitro cytokine profiles as indicators of relapse activity and clinical course in multiple sclerosis. 976 74

We investigate the regulation of plasminogen activator inhibitor-2 (PAI-2) in murine macrophages. PAI-2 mRNA was inducible by bacterial lipopolysaccharide (LPS) in primary cells and macrophage-like cell lines. Evidence is presented for a role for autocrine factors, including cyclooxygenase products but not the cytokines tumor necrosis factor alpha or interferon-beta (IFN-beta). PAI-2 mRNA levels generally varied inversely from those of its target, urokinase-type plasminogen activator (uPA), and the macrophage growth factor CSF-1, which induces uPA, inhibited PAI-2 expression in cells treated subsequently with LPS. Expression of PAI-2 was distinct from that of other LPS-inducible genes in terms of induction time course, LPS dose response, and sensitivity to co-stimulation with IFN-gamma. Induction of PAI-2 mRNA in subclones of the cell line RAW 264 was not uniform, reflecting heterogeneous expression in the parent line. The expression pattern of PAI-2 is discussed in terms of a possible role in LPS-induced pathology such as septicemia.
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PMID:Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin. 1041 Oct 6

The surface antigen CD14 is known to play a central role in the recognition of lipopolysaccharide by macrophages. We characterized a mutant cell line, J7.DEF.3, derived from a murine macrophage-like cell line, J774.1, to be defective in the ability to express the membrane-associated form of CD14 (mCD14) but not in the ability to release the soluble form of CD14 (sCD14), and used these parent and mutant cells to investigate the role of CD14 in lipopolysaccharide signaling. In response to lipopolysaccharide stimulation, mutant cells produced slightly less tumor necrosis factor than parent cells, and produced much less (negligible level) nitric oxide than parent cells. Production of both tumor necrosis factor and nitric oxide by parent cells upon lipopolysaccharide stimulation was suppressed by anti-CD14 serum. Expression of interferon-beta mRNA by stimulation with lipopolysaccharide, detected in parent cells, was barely detectable in mutant cells and in enzymatically mCD14-eliminated parent cells. Lipopolysaccharide-induced nitric oxide production in parent cells was suppressed by anti-(murine interferon-beta), and its production in the mutant cells appeared and increased dose dependently on exogenously supplied murine interferon-beta in the presence of lipopolysaccharide. These results provide new insight into the lipopolysaccharide signaling pathway, indicating that the lipopolysaccharide signal for interferon-beta production is transduced through a mCD14-dependent pathway and that the endogenously generated interferon-beta is an essential cofactor leading to nitric oxide production. Nuclear translocation of a transcription factor, nuclear factor kappaB, was observed in both parent and mutant cells following stimulation with a low dose of lipopolysaccharide, and mitogen-activated protein kinases were also activated in both types of cell, although a higher dose of lipopolysaccharide was required by the mutant cells than by the parent cells. These results indicate that these signaling factors may participate in the mCD14-independent lipopolysaccharide signaling pathway rather than in the mCD14-dependent interferon-beta-producing pathway.
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PMID:Important role of membrane-associated CD14 in the induction of IFN-beta and subsequent nitric oxide production by murine macrophages in response to bacterial lipopolysaccharide. 1060 48


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