Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberculosis remains one of the major infectious causes of morbidity and mortality in the world, yet the mechanisms by which macrophages defend against Mycobacterium tuberculosis have remained obscure. Results from this study show that murine macrophages, activated by interferon gamma, and lipopolysaccharide or tumor necrosis factor alpha, both growth inhibit and kill M. tuberculosis. This antimycobacterial effect, demonstrable both in murine macrophage cell lines and in peritoneal macrophages of BALB/c mice, is independent of the macrophage capacity to generate reactive oxygen intermediates (ROI). Both the ROI-deficient murine macrophage cell line D9, and its ROI-generating, parental line J774.16, expressed comparable antimycobacterial activity upon activation. In addition, the oxygen radical scavengers superoxide dismutase (SOD), catalase, mannitol, and diazabicyclooctane had no effect on the antimycobacterial activity of macrophages. These findings, together with the results showing the relative resistance of M. tuberculosis to enzymatically generated H2O2, suggest that ROI are unlikely to be significantly involved in killing M. tuberculosis. In contrast, the antimycobacterial activity of these macrophages strongly correlates with the induction of the L-arginine-dependent generation of reactive nitrogen intermediates (RNI). The effector molecule(s) that could participate in mediating this antimycobacterial function are toxic RNI, including NO, NO2, and HNO2, as demonstrated by the mycobacteriocidal effect of acidified NO2. The oxygen radical scavenger SOD adventitiously perturbs RNI production, and cannot be used to discriminate between cytocidal mechanisms involving ROI and RNI. Overall, our results provide support for the view that the L-arginine-dependent production of RNI is the principal effector mechanism in activated murine macrophages responsible for killing and growth inhibiting virulent M. tuberculosis.
 ...
PMID:Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. 155 82

Pretreatment of lipopolysaccharide (LPS)-responder C57BL/10ScSn mice with killed Propionibacterium acnes enhanced tumor necrosis factor alpha (TNF-alpha) production and lethality in response to a subsequent challenge with LPS. Sensitization to LPS increased with time of pretreatment and reached its maximum after 7 days. Sensitization was paralleled by gamma interferon (IFN-gamma) production that was detectable from day 3 onward. In contrast, a similar P. acnes pretreatment of LPS-nonresponder C57BL/10ScCr mice had no apparent effect on their high resistance to LPS. Challenge with LPS at any time during the 7-day period after P. acnes treatment led to no detectable TNF-alpha formation and caused no lethal effects. The absence of sensitization in C57BL/10ScCr mice was paralleled by an absence of IFN-gamma production. Administration of monoclonal IFN-gamma antibodies in C57BL/10ScSn mice up to day 3 of P. acnes treatment completely inhibited the overproduction of TNF-alpha by LPS. Anti-IFN-gamma administered later than day 3 had only a partial, although significant, inhibitory effect. Injection of appropriate amounts of anti-IFN-gamma also abolished the development of hypersensitivity to the lethal action of LPS. The effect of exogenously administered IFN-gamma on LPS sensitivity (e.g., TNF-alpha production, lethal effects) was studied in LPS-responder and nonresponder mice. Administration of murine recombinant IFN-gamma increased the sensitivity of C57BL/10ScSn mice to LPS and established LPS responsiveness in LPS-nonresponder C57BL/10ScCr and C3H/HeJ mice. The data provide evidence that IFN-gamma mediates the sensitization towards LPS induced by P. acnes.
 ...
PMID:Gamma interferon mediates Propionibacterium acnes-induced hypersensitivity to lipopolysaccharide in mice. 156 91

Two dimensional gel electrophoresis (2-D PAGE) and automated image analysis were used to study the effects of bacterial lipopolysaccharide (LPS) activation on secreted and cellular rat alveolar macrophage proteins. Primary alveolar macrophages were cultured and exposed to LPS in the presence of [35S]-methionine for 24 h. Image analysis of 2-D PAGE revealed that LPS treatment primarily modulated the proportions of several alveolar macrophage cellular proteins versus control in addition to limited protein induction and repression. The differential effect of LPS was more pronounced on secreted proteins where qualitative and quantitative differences from control cells were found. Immunoblots of secreted proteins with anti-tumor necrosis factor alpha (TNF alpha) and anti-interleukin-1 alpha(IL-1 alpha) antibodies identified these monokines from protein fluorographic patterns. IL-1 alpha was detected as a single polypeptide of 17 kD at pI = 5. Use of recombinant TNF alpha and monoclonal and polyclonal antibodies for immunodetection revealed the 17 kD form of TNF alpha as well as higher molecular weight species at 18 kD and 22 kD. Thus, analysis of radiolabeled rat macrophages treated with LPS reveals quantitative modulation of several cellular proteins as well as a distinctive pattern of secreted proteins which contain multiple monokine forms resolvable by 2-D PAGE.
 ...
PMID:Two dimensional gel electrophoresis of cellular and secreted proteins from rat alveolar macrophages after lipopolysaccharide treatment. 156 19

Because removal of monocytes from their natural milieu may alter their subsequent immune response patterns, we have compared the production of interleukin-1 beta (IL-1-beta) and tumor necrosis factor alpha (TNF-alpha) by cultured human whole blood to that by purified monocytes. IL-1-beta was released in a dose-dependent fashion by whole blood after stimulation with lipopolysaccharide. Immunofluorescence studies indicated that monocytes were the main producers of IL-1-beta in whole blood cultures. On a per monocyte basis, after stimulation with 10 micrograms/ml lipopolysaccharide, much more IL-1-beta was released by cultured whole blood (56.2 +/- 8.3 ng/10(6) monocytes) than by purified mononuclear cells maintained in tissue culture medium (7.1 +/- 2.6 ng/10(6) monocytes). However, maintaining purified mononuclear cells in autologous plasma restored IL-1-beta release to levels observed in whole blood cultures. IL-1-beta release by whole blood peaked at 9 to 12 hours, in contrast to release of TNF-alpha, which peaked at 6 hours. In parallel with protein production, IL-1-beta messenger RNA levels peaked later and were more sustained than TNF-alpha messenger RNA levels. These experiments suggest that plasma augments the stimulatory effect of endotoxin and that IL-1-beta and TNF-alpha have differing kinetics in whole blood.
 ...
PMID:Human whole blood interleukin-1-beta production: kinetics, cell source, and comparison with TNF-alpha. 158 10

It is well known that several inflammatory cytokines can modulate hepatocellular gene expression in a complex physiological process known as the hepatic acute-phase response. Since hepatitis B virus (HBV) characteristically induces a vigorous lymphomononuclear inflammatory response in the liver during acute and chronic hepatitis, it is possible that hepatocellular HBV gene expression may also be modulated by one or more of the cytokines produced by these cells. Using bacterial lipopolysaccharide (LPS) as a surrogate inducer of inflammatory cytokines in vivo, we have tested this hypothesis in a transgenic mouse model system. In experiments with two independent transgenic mouse lineages that express the HBV envelope region under the control of either HBV or cellular promoters, we observed a 50 to 80% reduction in the hepatic steady-state content of a 2.1-kb HBV mRNA following administration of a single intraperitoneal dose of LPS. The regulatory influence of several inflammatory cytokines known to be induced by LPS was also examined in this system. The negative regulatory effect of LPS was consistently reproduced by the administration of a single nontoxic dose of tumor necrosis factor alpha, and it was occasionally observed following the administration of high doses of alpha interferon and interleukin-6, while no effect was detectable in response to high-dose interleukin-1 alpha or to gamma interferon. These observations suggest that tumor necrosis factor alpha and perhaps other cytokines may activate a heretofore unsuspected intracellular pathway that negatively regulates HBV gene expression. The intracellular mechanism(s) responsible for this effect and its pathophysiologic relevance remain to be elucidated.
 ...
PMID:Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. 158 37

Macrophages and microglia are the principal target cells for human immunodeficiency virus (HIV) in brain, and as such, are likely participants in the neuropathology of HIV infection. In a model system for this process, we found that fluids from human monocyte cultures enhanced survival and differentiation of the neurons in fetal rat brain explants. In contrast, fluids from HIV-infected monocyte cultures were strongly toxic to neurons and paradoxically enhanced the proliferation of glial cells. Further, neuronotoxic activity in these fluids was mediated through activation of NMDA binding receptors on the neurons and was inhibited by any of several different NMDA antagonists. Neuronotoxic activity was directly related to contamination of the HIV virus stock with Mycoplasma arginini and M. hominis. Pure cultures of mycoplasma, bacterial lipopolysaccharide (LPS), or murine recombinant tumor necrosis factor alpha (rTNF alpha) each induced neuronotoxicity which exactly mirrored that induced by the contaminated HIV stock. It is likely that mycoplasma or components of the mycoplasma plasma membrane stimulate TNF alpha production by the glial cells in the brain explants. Indeed, careful depletion of glial cells in these explants prevented mycoplasma or LPS-mediated neuronotoxicity. No neuronotoxicity was evident with HIV-1 virus stock, HIV-1 gp120, or culture fluids from HIV-infected T cells or monocytes when these preparations were free of contamination by mycoplasma and LPS. These findings suggest caution in interpretation of those experiments in which similar contamination has not been rigorously excluded.
 ...
PMID:No direct neuronotoxicity by HIV-1 virions or culture fluids from HIV-1-infected T cells or monocytes. 159 56

Toxoplasma gondii alone does not induce tumor necrosis factor alpha (TNF-alpha) secretion by human monocytes and macrophages. Nevertheless, sera from infected patients with high titers of specific immunoglobulin G antibodies against T. gondii induce TNF-alpha secretion, which is significantly higher than the corresponding induction by negative sera (P less than 0.05). After incubation with the positive serum, parasites also induce secretion of this cytokine, but TNF-alpha levels are lower (11.4 to 71.8%) than those obtained with positive serum alone. Therefore, this secretion seems to be elicited in part by antibody-T. gondii complexes and/or another unidentified factor(s), probably different from lipopolysaccharide, interleukin-1, TNF-alpha, and gamma interferon. In this study, monocytes secreted more TNF-alpha into the culture fluid than macrophages did (P less than 0.05), and no correlation was observed between secretion of this cytokine by the monocytes and the intracellular multiplication of the parasites, evaluated by [3H]uracil incorporation. Sera from patients with other infections diseases did not induce secretion of TNF-alpha; however, serum free of antibodies to T. gondii, obtained from patients with leishmaniosis, also stimulated secretion of the cytokine.
 ...
PMID:Sera of patients with high titers of immunoglobulin G against Toxoplasma gondii induce secretion of tumor necrosis factor alpha by human monocytes. 161 37

Interleukin 1 (IL-1) production by A/J (A) and C57BL/6J (B6) mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) was determined. Strain A macrophages produced low levels of soluble IL-1 bioactivity compared with B6 macrophages. This defect was not reversed by indomethacin, interferon-gamma, phorbol myristate acetate, or calcium ionophore A23187. In contrast, cytosolic IL-1 bioactivity was similar in LPS-stimulated A and B6 macrophages. Western blotting revealed that A macrophage supernatants contained lower levels of both 17-kd IL-1 alpha and 17-kd IL-1 beta but similar levels of tumor necrosis factor alpha compared with B6 macrophages. Cytosolic levels of 31-kd pro-IL-1 alpha and also 31-kd pro-IL-1 beta were similar in A and B6 macrophages. Oligonucleotide probing indicated that A and B6 macrophages contained similar levels of IL-1 alpha and also IL-1 beta mRNA. These findings indicate that LPS-stimulated A macrophage culture supernatants contain low levels of both IL-1 alpha and IL-1 beta compared with B6 macrophages and that these defects in IL-1 production are posttranscriptionally regulated.
 ...
PMID:Defective lipopolysaccharide-induced production of both interleukin 1 alpha and interleukin 1 beta by A/J mouse macrophages is posttranscriptionally regulated. 161 93

Alveolar macrophages (AMs) are important in the host response to aerogenous pulmonary bacterial infections, such as Pasteurella haemolytica-induced pneumonia in cattle. Previous work has shown that AMs enhance P. haemolytica-mediated pulmonary endothelial cell (EC) damage in vitro. The purpose of this study was to determine the mechanism of AM-enhanced EC damage using an in vitro AM-EC coculture system consisting of AMs cultured on culture plate insert membranes and ECs in the underlying chamber. The addition of lipopolysaccharide (LPS) to the culture plate insert chamber resulted in EC damage indicated by 51Cr release, which was enhanced in the presence of AMs. To determine the role of AM-secreted cytokines, recombinant human interleukin 1 alpha (IL-1) or tumor necrosis factor alpha (TNF) was added to ECs simultaneously with varying concentrations of LPS. Although TNF and IL-1 alone had only marginal toxic effects on ECs, the simultaneous treatment of TNF or IL-1 with LPS greatly increased the LPS cytotoxic effect on ECs. In addition, IL-1 receptor antagonist eliminated the IL-1 enhancement of LPS-mediated EC toxicity. These results suggest that macrophage-secreted cytokines synergistically enhance LPS-mediated pulmonary EC damage.
 ...
PMID:Tumor necrosis factor alpha and interleukin 1 alpha enhance lipopolysaccharide-mediated bovine endothelial cell injury. 161 94

Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium.
 ...
PMID:Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system. 161 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>