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)

We examined the responsiveness of two factor-dependent macrophage cell lines, BDM-1 and its subclone, BDM-1W3, to bacterial lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) for their growth. LPS inhibited the M-CSF-dependent proliferation of BDM-1 cells but it had no effect on the proliferation of BDM-1W3 cells. LPS promoted DNA synthesis and supported the cell viability in the absence of CSFs in BDM-1 and BDM-1W3 cells, suggesting that the intracellular signals are transduced from the interaction of LPS with LPS-binding sites in BDM-1W3 cells as well as in BDM-1 cells. IFN-gamma inhibited the proliferation of BDM-1 and BDM-1W3 cells. However, BDM-1 cells were more susceptible to the inhibitory effect of IFN-gamma than BDM-1W3 cells. In contrast to LPS and IFN-gamma, TNF-alpha did not inhibit the proliferation of BDM-1 and BDM-1W3 cells. These cell lines should be useful for studying the regulatory mechanisms in CSF-dependent macrophage proliferation.
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PMID:Differential effects of bacterial lipopolysaccharide and interferon-gamma on proliferation of two factor-dependent macrophage cell lines. 164 63

The requirements for activation of anti-mycobacterial and anti-listerial activity of human monocytes were investigated. Human monocytes could be activated to display enhanced anti-mycobacterial activity by a 24-h treatment with lipopolysaccharide. The mediator induced by this treatment was identified as being tumour necrosis factor-alpha (TNF-alpha). Addition of recombinant TNF-alpha (rTNF-alpha) to the cultures of human monocytes for 24 h yielded comparable results (minimal dose required for induction of anti-mycobacterial activity, 10 U ml). Addition of anti-TNF-alpha antibody completely abrogated the effect. A similar treatment protocol failed to activate enhanced anti-listerial activity. To trigger anti-listerial activity, sequential treatment of human monocytes with rTNF-alpha and IL-2 was required. Treatment of monocytes with 10 U ml rTNF-alpha for 24 h followed by incubation in the presence of 200 U/ml of IL-2 for an additional 24 h yielded a reduction of listerial growth which was moderate but statistically significant (P less than 0.001). The activation of monocytes observed with rTNF-alpha/IL-2 treatment was (i) dependent on both cytokines; (ii) sequence dependent (i.e. when IL-2 was added prior to rTNF-alpha, no effect was observed); and (iii) absent in cells treated with one cytokine only. Enhancement of anti-listerial activity by sequential use of cytokines was not accompanied by an increase in oxidative burst, which indicated that oxidative mechanisms were not the reason for the observed Listeria monocytogenes growth restriction. Further support for this hypothesis was obtained after interferon-gamma treatment of human monocytes which led to an augmented PMA-inducible release of active oxygen radicals, but was not paralleled by growth restriction of L. monocytogenes. Our results indicate that TNF-alpha plays a crucial role in the activation of monocytes for growth restriction of intracellular microbes. Activation of human monocytes to restrict the growth of the facultative intracellular bacteria Mycobacterium avium intracellulare and L. monocytogenes, however, follows different patterns, the initial trigger in both cases being provided by TNF-alpha-induced signals.
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PMID:Induction of anti-mycobacterial and anti-listerial activity of human monocytes requires different activation signals. 164 23

Macrophages are uniquely responsive to bacterial lipopolysaccharide (LPS) for activation of a number of host defense functions and production of bioactive mediators. One potentially important mediator produced by LPS-stimulated macrophages is interferon (IFN-alpha/beta). In contrast to murine observations, we have observed that freshly isolated human monocytes, purified by counter-current centrifugal elutriation, do not produce interferon in response to LPS. This is not due to a lack of response to LPS, as assessed by the induction of other monokines, or to an incapacity for IFN production, since IFN was inducible by poly-I,C treatment of monocytes in the absence of any other exogenous stimulus. However, human monocytes can be primed for the production of IFN in response to LPS if they are cultured in the presence of either granulocyte-macrophage colony stimulating factor (GM-CSF) or interferon-gamma (IFN-gamma). The IFN secreted is of the alpha subtype. Monocytes primed with GM-CSF or IFN-gamma also maintained LPS responses for production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1). M-CSF did not prime monocytes for LPS-induced IFN production, although it did enhance production of TNF-alpha and promoted monocyte survival. Northern analysis indicated that the induction of IFN-alpha by LPS was regulated primarily at the mRNA level. The highly regulated production of IFN-alpha by monocytes/macrophages has important implications for autocrine action of interferons in the activation and differentiation of these cells.
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PMID:Regulation of interferon production by human monocytes: requirements for priming for lipopolysaccharide-induced production. 164 41

The effect of bacterial lipopolysaccharide (LPS) on the expression of class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) was determined by indirect immunofluorescent staining followed by flow cytometric analysis. LPS at concentrations higher than 0.01 micrograms/ml augmented class I MHC (HLA-A,B,C) expression on HUVEC in a concentration-dependent manner. Optimal augmentation, approximately sixfold compared with control, was seen with 10 micrograms/ml of LPS. Time-course experiments indicated that the augmentation was maximal on Day 4. In contrast, LPS had no effect on the induction of class II MHC (HLA-DR) molecules and at concentrations higher than 0.01 micrograms/ml inhibited the interferon-gamma(IFN-gamma)-induced class II MHC expression. The inhibition was about 60% at the concentration of 100 micrograms/ml of LPS. Interleukin-1 (IL-1) had a similar effect as LPS on class I and II MHC expression. However, LPS appeared to affect MHC expression directly and not through production of IL-1 or cyclo-oxygenase pathway products, since anti-IL-1 antibodies or an inhibitor of cyclo-oxygenase pathway products, indomethacin, failed to reverse the effects of LPS. These data stress the role of LPS as a direct modulatory factor of class I and II MHC expression on endothelial cells during the development of immune and inflammatory response against Gram-negative bacteria.
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PMID:Lipopolysaccharide augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells. 165 37

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.
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PMID:Inhibition of macrophage-activating cytokines is beneficial in the acute septic response. 165 39

Ethanol intoxication has been associated with bacterial pneumonia and tuberculosis. More recently, ethanol was shown to impair the capacity of pulmonary macrophages to produce superoxide anion and tumor necrosis factor (TNF). Furthermore, exposure to ethanol compromises macrophage's ability to respond to stimulation with TNF and granulocyte-macrophage colony-stimulating factor (GM-CSF), and kill an intracellular pathogen, Mycobacterium avium. Based on these previous findings, we examined whether exposure to ethanol affects superoxide anion production, synthesis of cytokines, and expression of membrane receptors to TNF on human monocyte-derived macrophages. Brief exposure to 10 or 50 micrograms/dl of ethanol significantly reduced the macrophage's response to a subsequent stimulus with phorbol ester (phorbol-12-myristate-13-acetate, PMA), and this unresponsive state lasts for approximately 6 h following removal of ethanol. When macrophages were then treated with lipopolysaccharide (LPS) in the presence of ethanol, high concentrations of TNF and GM-CSF were produced, but subsequent stimulation with LPS (second stimulus) was associated with significant impairment on synthesis and release of both TNF and GM-CSF. In addition, although ethanol had no effect on TNF binding to resting macrophages and to macrophages infected with M. avium, ethanol significantly reduced the expression of TNF receptors on interferon-gamma-stimulated macrophages. The ethanol-induced inhibition of macrophage function suggests potential mechanisms for suppression of the host's immune response and consequently increased susceptibility for infectious diseases.
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PMID:Ethanol affects release of TNF and GM-CSF and membrane expression of TNF receptors by human macrophages. 166 88

The expression of adhesion molecules in monocytes of patients with recent onset type I diabetes was analysed. Monocytes were identified as CD14-positive cells by flow cytometry. The percentage of monocytes expression LFA-1 alpha, ICAM-1 and HLA-DR was slightly lower in recent onset type I diabetes (n = 13) compared to normal subjects (n = 15) and was significantly decreased after activation of cells with lipopolysaccharide and interferon-gamma for 5-24 hr. Receptor densities on adhesion molecule-positive monocytes and the expression of LFA-1 beta were normal. These data indicate that monocyte trafficking is abnormal in recent onset type 1 diabetes.
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PMID:Decreased expression of adhesion molecules on monocytes in recent onset IDDM. 167

The mouse B-cell cell lymphoma 70Z/3 is a convenient model system in which to study the regulation of immunoglobulin synthesis. Three transcriptional activators of kappa (kappa) light chain synthesis have been identified for these cells: bacterial lipopolysaccharide (LPS), interferon-gamma (IFN), and interleukin-1 (IL-1). The response of the kappa gene in 70Z/3 cells to LPS is mediated by increases in two transcription factors: NF-kappa B and OTF-2. In contrast, IFN has no effect on either of these factors in 70Z/3 cells. We have isolated by immunoselection an LPS- IFN+ variant of 70Z/3 called 1.3E2. We show here that LPS treatment of these cells causes no increase in nuclear localization of either NF-kappa B or OTF-2. Although they have normal levels of cytoplasmic NF-kappa B, it cannot be activated by LPS or by phorbol 12-myristate 13-acetate (PMA) treatment of the cells. These experiments expand the genetic dissection of the molecular pathways of activation of kappa transcription in 70Z/3 cells.
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PMID:1.3E2, a variant of the B lymphoma 70Z/3, defective in activation of NF-kappa B and OTF-2. 168 72

Activated macrophages participate in inflammation by eliminating foreign cells, promoting wound healing, and modulating the immune response. A murine monoclonal antibody, designated anti-rat macrophage activator (RMA), was raised against alveolar macrophages (AM) activated with interferon-gamma (IFN-gamma) and phorbol myristate acetate (PMA). The RMA antigen is expressed by resident macrophages but not by other cells. Binding to AM by anti-RMA is not competitively inhibited by the murine monoclonal antibodies MRC OX-41, OX-42, and OX-43. Surface membrane expression of RMA antigens is upregulated by lipopolysaccharide, PMA, and tumor necrosis factor-alpha but not by IFN-gamma. Stimulation of AM with anti-RMA yields distinct ultrastructural alterations, as well as de novo protein and DNA synthesis. Immunoprecipitation of [35S]methionine metabolically labeled AM yields a 120 kD protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) that is not altered by chemical reduction. We conclude that the RMA antigen is macrophage specific and that binding of anti-RMA to AM promotes functional activities in a subset of these cells.
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PMID:Anti-RMA: a murine monoclonal antibody that activates rat macrophages. I. Distribution and characterization of the RMA antigen. 168 87

Treatment of HL-60 cells with 12-O-tetradecanoyl-phorbol 13-acetate (TPA) for 48 h induced expression of mRNA of beta A chain of activin A/erythroid differentiation factor. Under the same condition, interferon-gamma caused a slight increase in beta A chain mRNA, whereas 1 alpha, 25-dihydroxyvitamin D3, dimethylsulfoxide and all-trans-retinoic acid failed to induce this mRNA in HL-60 cells. Furthermore, 4 h-treatment with TPA or lipopolysaccharide (LPS) induced a marked increase in beta A chain mRNA levels in interferon-gamma-pretreated HL-60 cells. In the cells pretreated with 1 alpha, 25-dihydroxyvitamin D3, TPA and LPS induced as little increase in beta A chain mRNA as in the control cells. Neither alpha nor beta B chain mRNA was detected in any sample. These results indicate that interferon-gamma has a priming effect on the activation of activin A/erythroid differentiation factor gene by TPA or LPS in HL-60 cells.
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PMID:Inducible gene expression of activin A/erythroid differentiation factor in HL-60 cells. 169 Sep 89


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