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)

Based on our new concept of ontogenic inflammation, we have sought a substance which can prime macrophage in terms of the endogenous production of tumor necrosis factor (TNF). A lipopolysaccharide (LPSw) was found in wheat flour, purified and characterized. The molecular size of LPSw was about 5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it contained 3-deoxy-D-manno-octulosonic acid: 1, hexosamine: 4 and one phosphorus in a single molecule. LPSw can prime macrophage to release TNF when given intradermally, percutaneously or even orally in mice as well as in humans, in exactly the same way as intravenous administration of interferon gamma.
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PMID:Homeostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities. 160 47

The regulatory mechanisms which control the wide array of cellular responses to transforming growth factor beta (TGF beta) are not understood. This report presents evidence that down-regulation of TGF beta receptors on human monocytes may be one mechanism by which the effects of TGF beta are regulated. Treatment of monocytes with interferon gamma (IFN gamma) and lipopolysaccharide for 18 h reduced monocyte receptor number (approximately 400/cell) in a dose-dependent fashion by 89 and 78%, respectively, as determined by 125I-TGF beta binding. Incubation with other cytokines (granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor-1, interleukin-1, tumor necrosis factor alpha) did not alter the amount of TGF beta bound. The decrease in 125I-TGF beta binding could not be attributed to competition for receptor sites by secreted TGF beta. Instead, the decline in binding was due to a loss of type I TGF beta receptors, the subtype primarily expressed by monocytes, with no decrease in receptor affinity. Lipopolysaccharide-induced receptor loss was rapid (1-4 h), in contrast to the prolonged (12 h) decline induced by IFN gamma. Loss of receptors was accompanied by a diminished ability of the cells to respond to TGF beta with an induction of TNF alpha mRNA. Thus, this monocyte system is the first example of a heterologous agent causing the down-regulation of TGF beta receptors with a concomitant decline in a TGF beta-stimulated function.
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PMID:Modulation of monocyte type I transforming growth factor-beta receptors by inflammatory stimuli. 165 92

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) on primary cultures of human adult oligodendrocytes and astrocytes. Under unstimulated conditions, low levels of ICAM-1 immunoreactivity were identified on both oligodendrocytes (less than 50%) and astrocytes (less than 30%). After 48 hours' exposure to immune mediators, such as culture supernatant of phytohemagglutinin (PHA)-stimulated lymphocytes, interferon gamma (IFN-gamma; 1,000 U/ml), tumor necrosis factor alpha (TNF-alpha; 2,000 U/ml), interleukin-1 alpha (IL-1 alpha; 1,000 U/ml) and lipopolysaccharide (LPS; 50 micrograms/ml), ICAM-1 expression on both cell types was markedly increased in terms of intensity and cell numbers. IFN-gamma and culture supernatant of PHA-stimulated lymphocytes were the most potent inducers of ICAM-1 among the mediators tested, while TNF-alpha, IL-alpha and LPS were less effective, although variations were observed among cultures derived from different donors. Cytokine-induced expression of ICAM-1 on glial cells may play a role in mediating lymphocyte-glial cell interactions at sites of inflammation in the central nervous system.
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PMID:Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human oligodendrocytes and astrocytes. 167 9

The recent demonstration of the ability of human polymorphonuclear neutrophils (PMN) to secrete various cytokines in response to the granulocyte activator granulocyte-macrophage colony-stimulating factor (GM-CSF) but not to other cytokines, has led to the identification of PMN as biosynthetically active cells. In this study we have investigated the ability of PMN to secrete interleukin-6 (IL-6), a molecule known to be involved in inflammatory reactions. Using RNA blotting analysis and bioassays, we show that PMN could be induced to synthesize transcripts specific for IL-6, indistinguishable in size from IL-6 mRNA produced by activated human macrophages. Consequently, PMN released IL-6-like activity into their culture supernatants that could be neutralized by monospecific anti-IL-6 antibody. Interleukin-6 secretion by PMN, however, required previous stimulation with GM-CSF or tumor necrosis factor-alpha (TNF-alpha), whereas other cytokines, including interleukin-3 (IL-3), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), interferon gamma (IFN-gamma), and lymphotoxin (LT), failed to induce IL-6 mRNA accumulation and protein secretion by PMN. Similar to GM-CSF and TNF-alpha, other compounds, including the inhibitor of protein synthesis cyclohexemide (CHX), endotoxin (Escherichia coli-derived lipopolysaccharide), and phorbol myristate acetate (PMA) (but not the chemoattractant N-formyl-methionyl-leucyl-phenylalanine [FMLP]), induced detectable levels of IL-6 transcripts in PMN.
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PMID:Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. 169 93

In this report we have analyzed the effect of recombinant interleukin 2 (rIL 2) and rIL 2-activated natural killer (NK) cells on the production of immunoglobulin isotypes by lipopolysaccharide (LPS)-stimulated spleen cells from nude mice. We found that rIL 2 induced a dose-dependent increase of IgG2a secretion and a concomitant inhibition of the secretion of other Ig isotypes. The analysis of the phenotype of LPS- and LPS+ rIL 2-stimulated nude spleen cells showed the appearance of a Thy-1+ asialo GM-1+slgM-CD3-CD4-CD8- cell population in the presence of rIL 2. A population with a similar phenotype was generated upon stimulation of spleen cells from nude mice with rIL 2 alone. These cells lysed YAC-1 cells, did not contain the alpha or gamma transcripts encoding the corresponding T cell receptor chains and are therefore NK cells activated by rIL 2. In co-culture experiments, these cells selectively increased the secretion of IgG2a by LPS-stimulated splenocytes from nude mice. The IgG2a induction triggered by rIL 2-activated NK cells, as well as that triggered by rIL 2, were blocked by an anti-interferon gamma monoclonal antibody. Thus, rIL 2 activated-NK cells enhance the production of IgG2a by secreting interferon-gamma.
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PMID:Recombinant interleukin 2-activated natural killer cells regulate IgG2a production. 169 33

We have previously cloned the murine homolog of cDNA for the human myelomonocytic differentiation antigen, CD14. We synthesized three hydrophilic peptides derived from the predicted amino acid sequence of murine CD14 (mCD14), designated MS7.1, MS7.2, and MS7.3, respectively, and raised antisera against them. Each antiserum showed specific reactivity to the same peptide used for immunization. One of the anti-mCD14 antisera directed against MS7.3 peptide (AMS7.3) demonstrated the highest titer and definitively reacted with monocytic cell lines, inflammatory polymorphonuclear cells, and macrophages. Significant cross-reactivity of AMS7.3 was observed in the human monocytic cell line, THP-1. COS-1 cells transfected with MS7 cDNA expressed an antigen recognized by AMS7.3. Resident peritoneal and alveolar macrophages both expressed mCD14. mCD14 expression in peritoneal but not alveolar macrophages increased after treatment with lipopolysaccharide. Expression of mCD14 varied among monocytic cell lines and roughly paralleled the mRNA levels except in MI cells. SDS-PAGE and isoelectric focusing analysis of immunoprecipitated mCD14 showed that mCD14 was a 53 kd disulfide-linked protein with a pI of 4.5-5.1. Reduction of molecular weight by endo F treatment demonstrated that mCD14 was an N-linked glycoprotein. Since mCD14 is shed from the cell surface membrane by phosphatidylinositol-specific phospholipase C treatment, the indication is that mCD14 is a phosphatidylinositol-linked protein. The soluble form of mCD14 was detectable. Treatment with anti-mCD14 before interferon gamma (IFN gamma) stimulation significantly enhanced IFN gamma-induced H-2 antigen expression in the macrophage cell line.
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PMID:Molecular and physiological properties of murine CD14. 170 50

Leukocyte adherence to endothelium is in part mediated by the transient expression of endothelial-leukocyte adhesion molecule 1 (ELAM-1) on endothelial surfaces stimulated by tumor necrosis factor alpha (TNF), interleukin (IL) 1, or bacterial lipopolysaccharide (LPS). The intracellular factors controlling induction of ELAM-1 mRNA and protein are unknown. In nuclear runoff experiments with cultured human umbilical vein endothelial cells (HUVEC), we demonstrate that transcriptional activation of the ELAM-1 gene occurs following stimulation with TNF. Sequence analysis of the 5' flanking region of the ELAM-1 gene reveals consensus DNA-binding sequences for two known transcription factors, NF-kappa B and AP-1. Gel mobility shift assays demonstrate that TNF, IL-1, or LPS (but not IL-2, IL-4, IL-6, interferon gamma, histamine, or transforming growth factor beta) induces activation of NF-kappa B-like DNA binding activity in HUVEC. In contrast, neither TNF, IL-1, nor LPS activates proteins that bind to an AP-1 consensus sequence under these experimental conditions. Phorbol 12-myristate 13-acetate, a known activator of protein kinase C (PKC), weakly induces NF-kappa B-like activity, ELAM-1 mRNA, and ELAM-1 surface expression in HUVEC. However, TNF, IL-1, and LPS do not activate PKC in HUVEC at doses that strongly induce NF-kappa B-like protein activation and ELAM-1 gene expression. PKC blockade with H7 does not inhibit activation of these NF-kappa B-like proteins but does inhibit ELAM-1 gene transcription. We conclude that PKC-independent activation of NF-kappa B in HUVEC with TNF, IL-1, or LPS is associated with, but not sufficient for, activation of ELAM-1 gene transcription.
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PMID:Activation of endothelial-leukocyte adhesion molecule 1 (ELAM-1) gene transcription. 171 80

A soluble nitric oxide (NO) synthase activity was purified 426-fold from a mouse macrophage cell line activated with interferon gamma and bacterial lipopolysaccharide by sequential anion-exchange, affinity, and gel filtration chromatography. SDS/PAGE of the purified NO synthase gave three closely spaced silver-staining protein bands between 125 and 135 kDa. When assayed in the presence of L-arginine, NADPH, tetrahydrobiopterin, FAD, and reduced thiol, purified NO synthase had a specific activity of 1313 nmol of NO2- plus NO3- per min per mg. The apparent Km of the enzyme for L-arginine and NADPH was 2.8 and 0.3 microM, respectively. Addition of calcium ions with or without calmodulin did not increase the activity of the purified enzyme, and NO synthesis was not altered by calmodulin inhibitors. Gel filtration chromatography indicated that the induced NO synthase was catalytically competent as a dimer of approximately 250 kDa but could be dissociated into inactive monomers of approximately 130 kDa in the absence of L-arginine, FAD, and tetrahydrobiopterin. Upon heat denaturation, NO synthase released 1.1 mol of FAD and 0.55 mol of FMN per mol of 130-kDa subunit. Thus, inducible macrophage NO synthase differs in several respects from constitutive NO synthases and is one of very few eukaryotic enzymes containing both FAD and FMN.
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PMID:Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: an FAD- and FMN-containing flavoprotein. 171 79

Macrophages derived in vitro from bone marrow progenitors (bone marrow-derived macrophages, BMDMs) using either macrophage colony-stimulating factor (CSF-1) or granulocyte-macrophage colony-stimulating factor (GM-CSF) as the myelopoietic stimulus display differential functional, morphological, and mRNA phenotypes. The data presented here demonstrate further that CSF-1- and GM-CSF-derived BMDMs differ in immunologic capacity. GM-CSF-derived BMDMs, when compared to CSF-1-derived BMDMs, showed greater cytolytic activity against tumor necrosis factor alpha (TNF-alpha)-resistant, but not TNF-alpha-sensitive, tumor targets. In contrast, CSF-1-derived BMDMs produced nitrite in response to lipopolysaccharide (LPS) alone, whereas GM-CSF-derived BMDMs required interferon gamma plus LPS treatment. The two BMDM populations also showed differential sensitivities to LPS for secretion of TNF-alpha and nitrite, but the maximal inducible amounts of these factors and prostaglandin E2 were similar between the BMDM populations. Lastly, GM-CSF-derived but not CSF-1-derived BMDMs showed an L-arginine-dependent listeriacidal activity. These results show that the functional heterogeneity of CSF-1- and GM-CSF-derived macrophages is limited and appears to result largely from differences in the activational signals required by each BMDM population to elicit a given function.
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PMID:Differential immunocompetence of macrophages derived using macrophage or granulocyte-macrophage colony-stimulating factor. 174 Jun 46

The murine suppressive factor of allergy (SFA) has been purified from a T-cell hybridoma and found to consist of two functionally and biochemically distinct protein molecules. One protein (17 kDa) modulates the low-affinity Fc receptor for IgE on lymphocytes (i.e., CD23); it decreases the binding avidity of IgE to CD23-bearing B cells without affecting quantitative expression of CD23 and is thus designated epsilon-receptor-modulating protein. The second protein (30 kDa) suppresses IgE biosynthesis (i.e., SFA). This purified SFA suppresses interleukin 4-induced IgE and IgG1 synthesis by lipopolysaccharide-activated spleen cells but has no effect on other antibody isotypes; since the activity of SFA is not blocked by anti-interferon gamma monoclonal antibody, it is thus distinct from interferon gamma. The data presented indicate that epsilon-receptor-modulating protein and SFA are protein molecules that are involved in modulating the CD23 molecule and IgE antibody synthesis, respectively.
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PMID:Purification of murine suppressive factor of allergy into distinct CD23-modulating and IgE-suppressive proteins. 182 84


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