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)

Tumor necrosis factor (TNF)-sensitive (LM) and -insensitive (P815) target cell lines were used to examine the role of TNF in both the activation and lytic phases of macrophage-mediated lysis. LM cells were lysed spontaneously by thioglycolate-elicited macrophages in an 18-h assay (media or activating agents added with targets) or 36-h assay (macrophages cultured with media or activating agents for 18 h, washed, and targets added for a subsequent 18 h). In contrast, P815 cells were lysed only in the 36-h assay by macrophages exposed to appropriate activation signals. Using antibody to murine TNF, it was shown that lysis of LM cells but not P815 cells was TNF mediated. The addition of lipopolysaccharide (LPS) to the 18-h assay resulted in augmented LM killing. This was probably due to the fact that LPS stimulates macrophages to produce TNF. Conversely, when macrophages were pretreated with LPS for 18 h, washed, and assessed for lytic activity during the subsequent 18 h, lysis of LM cells was reduced relative to the endogenous level. Although macrophage lysis of P815 was not mediated by TNF, the addition of TNF to macrophage activation cultures facilitated LPS triggering of cytolytic activity against P815. Similarly, the addition of TNF to the activation cultures partially prevented the LPS-induced reduction in macrophage-mediated LM cell lysis. Taken together, these data suggest that TNF may act as an autocrine signal during macrophage activation, in addition to being directly lytic to a select number of sensitive target cell lines.
 ...
PMID:Role of tumor necrosis factor in macrophage activation and tumoricidal activity. 341 99

We have studied the role of prostaglandin E2 on the modulation of tumor necrosis factor by immunologically elicited and lipopolysaccharide treated murine macrophages. Indomethacin, a potent inhibitor of prostaglandin E2 production, caused a dose dependent augmentation of lipopolysaccharide induced tumor necrosis factor production (2-3 fold at 10(-7) molar). Tumor necrosis factor was released into the extracellular environment and no activity was found to be associated with membrane or cytosolic fractions. Prostaglandin E2 added to the lipopolysaccharide treated cultures suppressed tumor necrosis factor in a dose dependent manner. In these studies, 10(-7) molar PGE2 reduced tumor necrosis factor production to basal levels. These data suggest that PGE2 may be a potent autoregulatory factor that dramatically influences tumor necrosis factor production.
 ...
PMID:Regulation of macrophage tumor necrosis factor production by prostaglandin E2. 345 61

Tumor necrosis factor (TNF) was detected in the sera of normal mice, unprimed by reticuloendothelial system (RES) stimulators, when such mice were injected with lipopolysaccharide (LPS). Amounts of TNF were approximately 200-fold less than those found in Corynebacterium parvum-primed mice. No TNF activity was detected in the sera of mice not administered LPS. TNF induction in unprimed mice was refractory to repeated administration of endotoxin, thus exhibiting a tolerance phenomenon. TNF produced in unprimed mice eluted similarly to Mycobacterium bovis, strain BCG-primed TNF on Sephacryl S-200 and DEAE Sephacel columns and was neutralized by rabbit antisera raised to partially purified BCG-primed TNF. When BALB/c mice having 7-day old subcutaneous Meth A tumor implants were administered TNF antiserum, endotoxin-induced hemorrhagic necrosis was largely prevented. These findings strongly suggest that endotoxin-induced hemorrhagic necrosis of tumors is mediated through TNF production and action.
 ...
PMID:Production of tumor necrosis factor in unprimed mice: mechanism of endotoxin-mediated tumor necrosis. 352 51

Pentamidine effects on the interferon-gamma- or interferon-gamma plus bacterial lipopolysaccharide-induction of nitric oxide synthase in the macrophage cell line RAW 264.7, determined by measuring nitrite release into culture supernatants, were investigated. At concentrations above 10 microM, pentamidine caused visible toxic effects including cell lysis which also was assessed by measuring lactic dehydrogenase release. A progressive inhibitory effect of pentamidine could not be clearly dissociated from these toxic and lytic effects which were extensive at 100 microM. At 1 microM pentamidine, the dose response dependence of nitrite formation on interferon-gamma was not affected. Tumor necrosis factor-alpha caused some enhancement of interferon-gamma-induced nitrite release only at high doses of 100 and 10,000 unit/ml. Pentamidine had no effect on isolated inducible nitric oxide synthase from RAW 264.7 cells but inhibited the constitutive enzyme from pork cerebellum non-competitively. The lack of any stimulatory effect of pentamidine on nitrite production in RAW 264.7 cells suggests that NOS induction and NO production by macrophages is not the mechanism of the antimicrobial effects of this drug.
 ...
PMID:Pentamidine does not interfere with nitrite formation in activated RAW 264.7 macrophages but inhibits constitutive brain nitric oxide synthase. 747 46

Nitric oxide is a highly reactive mediator released in the liver by hepatocytes, Kupffer cells and endothelial cells during endotoxin-induced inflammation. In this study we determined whether Ito cells also produce nitric oxide after exposure to endotoxin. For induction of endotoxemia, rats were injected intravenously with Escherichia coli lipopolysaccharide (2.5 mg/kg). Ito cells were isolated from the animals 48 hr later by means of in situ perfusion of the liver with protease and collagenase followed by purification on an arabinogalactan gradient. Ito cells from untreated and endotoxemic rats were found to produce low levels of nitric oxide in response to interferon-gamma. In both cell types, this response depended on L-arginine and was blocked by NG-monomethyl-L-arginine, a specific nitric oxide synthase inhibitor. Cells from rats treated with endotoxin produced significantly more nitric oxide than did cells from untreated animals; this was due, at least in part, to increased expression of protein for an inducible form of nitric oxide synthase. These cells also responded to stimulation with lipopolysaccharide in vitro, as well as the combination of interferon-gamma and lipopolysaccharide, which was synergistic in stimulating nitric oxide production. Tumor necrosis factor-alpha and macrophage colony-stimulating factor were also found to stimulate nitric oxide production by Ito cells from endotoxemic rats. In addition, in these cells, tumor necrosis factor-alpha synergized with interferon-gamma in inducing nitric oxide production. The combination of interferon-gamma and lipopolysaccharide was also found to inhibit Ito cell DNA synthesis, as measured on the basis of [3H]-thymidine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Induction of hepatic Ito cell nitric oxide production after acute endotoxemia. 752 4

Tumor necrosis factor (TNF)-alpha has been postulated to play an important physiologic as well as pathologic role within the developing brain. In the present study, we found that human fetal microglial cells released abundant amounts of TNF-alpha upon stimulation with lipopolysaccharide (LPS). Treatment of microglial cell cultures with antibodies specific to interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta augmented LPS-stimulated release of TNF-alpha. Each of these cytokines dose-dependently suppressed TNF-alpha release. Also, TNF-alpha mRNA expression was inhibited by each of these cytokines. By way of contrast, treatment of microglial cell cultures with IL-alpha or IL-1 beta alone or in the presence of LPS, resulted in increased release of TNF-alpha, and IL-1 stimulated the expression of TNF-alpha mRNA. These findings suggest that these cytokines are likely to modify the beneficial and harmful effects of TNF-alpha within the developing brain.
 ...
PMID:Tumor necrosis factor-alpha production by human fetal microglial cells: regulation by other cytokines. 755 42

Tumor necrosis factor-alpha (TNF-alpha) is a pathogenic factor in bacterial meningitis. The effect of thalidomide on TNF-alpha production by microglia, the resident macrophages of the brain, was evaluated. In primary human fetal microglial cell cultures stimulated with lipopolysaccharide or lipoarabinomannan, thalidomide inhibited TNF-alpha release in a dose-dependent manner. The inhibitory effect of thalidomide was similar to that of dexamethasone, although expression of TNF-alpha mRNA in microglial cells was reduced only by thalidomide. The results of this in vitro study suggest that thalidomide could have therapeutic potential in gram-negative bacterial and tuberculous meningitis.
 ...
PMID:Thalidomide inhibits tumor necrosis factor-alpha production by lipopolysaccharide- and lipoarabinomannan-stimulated human microglial cells. 756 Nov 98

Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta produced by glial cells have been proposed bo play a role in various neurodenegerative diseases. The interaction of these two cytokines, however, is unknown. We tested the hypothesis that the TNF-alpha released from lipopolysaccharide (LPS)-treated murine microglial cells would stimulate the release of TGF-beta, which in turn would control TNF-alpha production. Treatment of murine microglial cell cultures with LPS resulted in an acute release of TNF-alpha (peak by 8 hr) followed by delayed release of bioactive TGF-beta (peak by 48 hr). Anti-TNF-alpha antibody significantly inhibited LPS-stimulated TGF-beta production, suggesting the involvement of TNF-alpha in TGF-beta production. Also, exogenous TNF-alpha induced in a dose-dependent fashion microglial cell expression of TGF-beta 1 mRNA and release of TGF-beta. Exogenous TGF-beta, on the other hand, suppressed LPS-stimulated TNF-alpha release. These findings suggest an autoregulation of microglial cell TNF-alpha production by TGF-beta which may limit inflammation-associated brain injury.
 ...
PMID:Tumor necrosis factor-alpha mediates the release of bioactive transforming growth factor-beta in murine microglial cell cultures. 758 47

Tumor necrosis factor-alpha (TNF-alpha) is produced and secreted from monocytes in response to activation with lipopolysaccharide (LPS). The role of Na+ and HCO3- in the production of TNF-alpha by monocytes was investigated; it was observed that replacement of Na+ in the culture medium with sucrose or choline chloride inhibited TNF-alpha production completely. The addition of Na+ to Na(+)-free culture medium restored TNF-alpha production with an EC50 value of 35 mmol/l. The amiloride analog 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na+/H+ antiporter, inhibited TNF-alpha production with an EC50 of 3.3 microM. Without HCO3- in the culture medium TNF-alpha production was inhibited by 92%. Total protein synthesis was inhibited by 85% in the absence of Na+ but did not change in the absence of bicarbonate in the culture medium. Intracellular pH (pHi) which increased from 6.90 in control monocyte to 7.40 in response to activation with LPS was abrogated to pHi of 6.95 in the absence of Na+ but did not change in the absence of HCO3- in the culture medium. In the presence of 100 microM phloretin or DIDS the pHi of activated monocyte was reduced to control value, TNF-alpha production was inhibited completely and total protein synthesis was inhibited by 61%. These data suggest that (1) TNF-alpha production, as other proteins, is dependent on the pHi of monocytes,and (2) TNF-alpha production, in contrast to total protein, is modulated by Na(+)-dependent HCO3-.
 ...
PMID:Modification of tumor necrosis factor-alpha (TNF-alpha) production by the Na(+)-dependent HCO3- cotransport in lipopolysaccharide-activated human monocytes. 759 12

We have studied the effects of exogenous tumor necrosis factor-alpha, interleukin-1 beta, and lipopolysaccharide-induced interleukin-1 beta on receptor-mediated endocytosis in primary cultures of liver sinusoidal endothelial cells. Tumor necrosis factor-alpha and interleukin-1 beta enhanced endocytosis via the scavenger and mannose receptors in a dose-time dependent manner, while the function of the collagen receptor remained unaffected. The modulatory effects of the cytokines were blocked by adding specific inhibitors for both cytokines. Results from studies on binding (4 degrees C) and internalization and degradation (37 degrees C) of ligands indicate that the increased scavenger capacity of liver sinusoidal endothelial cells resulting from exposure to the inflammatory mediators was due to increased rate of intracellular transport of endocytosed ligands to lysosomes, rather than to increased binding to receptors.
 ...
PMID:Differential cytokine-mediated modulation of endocytosis in rat liver endothelial cells. 761 12


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