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 have previously shown that the antiviral state of explanted mouse peritoneal macrophages (PM) decays during in vitro culture and that this decay is much more rapid in Lpsd PM than it is in Lpsn PM. Moreover, Lpsn PM can transfer the antiviral state to other cells, whereas Lpsd PM cannot. In vitro treatment of Lpsn PM with different agents [i.e., bacterial lipopolysaccharide (LPS), interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, macrophage colony-stimulating factor (M-CSF) and antibody to Mac-1 antigen] induced an antiviral state to vesicular stomatitis virus (VSV) which was inhibited by antibodies to IFN-beta. Treatment of Lpsn PM with LPS or IFN-gamma resulted in greater accumulation of IFN-beta mRNA, whereas no change in the barely detectable levels of IFN-alpha mRNA was observed. Marked accumulation of IFN-beta mRNA was also observed in PM after TNF-alpha treatment. M-CSF and IFN-gamma (but not LPS) also induced an IFN-mediated antiviral state in Lpsd PM. Low levels of spontaneous transcription of IFN-beta mRNA were detected in nuclei from Lpsd PM. Treatment of Lpsd PM with IFN-gamma for 3 h resulted in the accumulation of IFN-beta mRNA without any concomitant increase in the transcription of the IFN-beta gene, as determined by run-on transcription assays with isolated nuclei. The addition of as little as I international unit/ml of IFN-gamma to PM resulted in a 100-fold inhibition of VSV yield. As antibodies to IFN-alpha/beta inhibited only a portion of the IFN-gamma-induced antiviral state, such an antiviral state might reflect the synergism between IFN-gamma and endogenous IFN-beta. In fact, the addition of low doses of both IFN-gamma and IFN-beta to either Lpsn or Lpsd PM resulted in synergistic antiviral effects. In vivo treatment of Lpsd mice with granulocyte-macrophage (GM)-CSF, M-CSF, IFN-gamma or Newcastle disease virus rendered peritoneal cells capable of transferring an antiviral state. These results indicate that (i) various stimuli can induce IFN-beta production by PM, (ii) Lpsd PM spontaneously transcribe low levels of IFN-beta mRNA, even though they cannot transfer an antiviral state, (iii) different stimuli, but not LPS, induce a normal IFN response in Lpsd PM, (iv) IFN-gamma increases the accumulation of IFN-beta mRNA in Lpsd PM by post-transcriptional mechanisms and (v) IFN-gamma may act synergistically with endogenous IFN-beta in inducing a potent antiviral state to VSV in PM.
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PMID:Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. 170 75

Tumor necrosis factor (TNF) is a cytokine which stimulates osteoclastic bone resorption and inhibits collagen synthesis in vitro. In this study the effect of human cholesteatoma debris and its constituents on the production of TNF-alpha by human monocytes in vitro was studied. Cultured human peripheral monocytes secreted TNF into the culture medium when exposed to cholesteatoma debris in a dose-dependent manner. The TNF production, however, was partially inhibited by the treatment of the debris with polymyxin B which inhibits biological activities of lipopolysaccharide (LPS). When individual constituents of cholesteatoma debris, i.e. keratin, cholesterol, lauric acid and LPS, were added to the cultured monocytes at concentrations equivalent to those in the debris, significant production of TNF was observed only with the keratin and LPS. These data suggest that cholesteatoma debris is a potent activator of the TNF production of human monocytes in vitro, and that LPS and keratin are responsible for the production.
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PMID:Cholesteatoma debris as an activator of human monocytes. Potentiation of the production of tumor necrosis factor. 170 75

Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.
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PMID:T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. 173 Sep 29

Chemotactic cytokines play a critical role in recruiting leukocytes to sites of tissue injury. Interleukin-8 (IL-8) is a chemotactic cytokine secreted by a variety of cells (eg, monocytes, endothelial cells, fibroblasts) during the inflammatory response. In this report, the authors demonstrate that human transitional cell carcinomas and renal cell carcinomas have the capacity to elaborate IL-8 in response to the inflammatory mediators IL-1 beta and tumor necrosis factor (TNF)-alpha. All cell lines expressed high levels of IL-8 mRNA on stimulation with either IL-1 beta or TNF-alpha, but not lipopolysaccharide; one expressed the gene constitutively. The authors selected one transitional cell carcinoma cell line (UM-UC-9) and one renal cell carcinoma cell line (UM-RC-5) for further study. Both displayed a time- and dose-dependent increase in steady-state levels of IL-8 mRNA in response to IL-1 beta and TNF-alpha. Specific mRNA was detectable by 1 hour after stimulation. Secretion of antigenic IL-8 measured by enzyme-linked immunosorbent assay into culture supernatants reflected the kinetics of mRNA expression. Because heat-inactivated TNF-alpha failed to induce synthesis of IL-8 mRNA, and cycloheximide augmented TNF-alpha-induced synthesis, IL-8 expression appears to be a stimulus-specific primary induction phenomenon. As with other inflammatory mediators whose mRNA contains a 3' AU-rich sequence (eg, IL-2, TNF-alpha), the half-life of IL-8 mRNA was short, less than 1 hour. Our data suggest that secretion of IL-8 by malignant cells may partly account for the inflammatory infiltrates associated with some malignant neoplasms.
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PMID:Cytokine-induced gene expression of interleukin-8 in human transitional cell carcinomas and renal cell carcinomas. 173 30

Effect of 1,25(OH)2D3 and glucocorticoids on production of TNF-alpha by human peripheral blood adherent cells (HPBAC) was investigated. TNF-alpha was measured by ELISA method using monoclonal antibody against human recombinant THF-alpha. Maximal TNF-alpha production by HPBAC was observed in 4 to 8 hr after incubation when these cells were cultured for 24 hr with 10 micrograms/ml lipopolysaccharide (LPS), 10 ng/ml 12-o-tetradecanoyl-phorbol-13-acetate (TPA) and 10(-5) M indomethacin (INDM). When graded concentration of 1,25(OH)2D3 was added to HPBAC in the presence of above stated dose of LPS, TPA and INDM, a significant suppression of TNF-alpha production was first observed at the concentration of 10(-8) M (P less than 0.05). Similar significant suppressive effect was also observed by adding hydrocortisone and dexamethasone at the concentration of 10(-8) M (P less than 0.05) and 10(-7) M (P less than 0.05), respectively. These results may suggest that 1,25(OH)2D3 has the same inhibitory effect on monocyte/macrophage function as glucocorticoids.
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PMID:Suppressive effect of 1,25(OH)2D3, and glucocorticoids on production of tumor necrosis factor-alpha by human peripheral blood adherent cells. 174 43

The effect of misoprostol (M) on IL-1 beta, TNF-alpha, and lipid mediator release (assessed by RIA) by adherent (assessed by electron microscopy) human monocytes were studied in vitro. Human monocytes stimulated with E. Coli-derived lipopolysaccharide showed an increase in both IL-1 beta and TNF-alpha release. Incubation of the monocytes with LPS and M (18 hrs.), resulted in a reduction of both IL-1 beta and TNF-alpha levels. Leukotriene B4 levels did not increase in response to LPS or M. LPS also caused an increase in thromboxane (TXB2). M decreased TXB2 levels. 6-keto PGF1 alpha (6KP). Incubation with LPS and M stimulated release. LPS caused an increase in PGE2 levels. M (100 microM) caused an increase in PGE2 levels, M (1 microM) had no effect on PGE2. These data suggest a possible immunomodulatory role for misoprostol in inflammatory diseases.
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PMID:Effects of the prostaglandin analogue misoprostol on inflammatory mediator release by human monocytes. 179 47

The effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogue 22-oxacalcitriol (OCT), which was reported to have very weak bone resorbing activity, on the production of tumor necrosis factor (TNF)-alpha was investigated. Mononuclear cells (MNC; 10(6)/ml) were incubated in 5% FCS/RPMI-1640 medium containing 1 microgram/ml lipopolysaccharide (LPS) in the presence or absence of 10(-8) M 1,25(OH)2D3 or 10(-8) M OCT for up to 96 h. Both 1,25(OH)2D3 and OCT suppressed TNF-alpha release by LPS-stimulated mononuclear cells, from the early to late stage of the incubation period, while neither 1,25(OH)2D3 nor OCT shifted the peak time point of TNF-alpha release clearly. MNC (10(6)/ml) were incubated with 1 microgram of LPS in the presence of various concentrations of 1,25(OH)2D3 or 10(-8) M OCT for 48 h. 1,25(OH)2D3 reduced TNF-alpha levels of LPS-stimulated MNC culture supernatant at 48 h in a dose-dependent manner. The half-maximal dose (ED50) for this suppressive effect was 3.7 x 10(-9) M. OCT decreased TNF-alpha levels of culture supernatant at 48 h with a half-maximal dose of 7.8 x 10(-11) M, which indicates that it is approximately 50 times more potent than that of 1,25(OH)2D3. These results indicate that OCT may be applicable as an immunosuppressive agent with limited calcium metabolic activity.
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PMID:The weak calcemic vitamin D3 analogue 22-oxacalcitriol suppresses the production of tumor necrosis factor-alpha by peripheral mononuclear cells. 180 Mar 16

We examined the effect of tebufelone, a dual cyclooxygenase (CO)/5-lipoxygenase (LO) inhibitor, on the synthesis, secretion and gene expression of interleukin (IL) 1 beta and tumor necrosis factor (TNF)-alpha by human peripheral blood mononuclear cells (PBMC). Basal concentrations of immunoreactive IL 1 beta and TNF-alpha after 18-24 h, in the absence or presence of tebufelone (less than or equal to 12.5 microM), were near the limit of detection (100 pg/ml). By contrast, preincubation (1 h) of cells, in amounts of tebufelone which decrease the formation of leukotriene (LT) B4, markedly enhanced (up to 500%) the synthesis of IL 1 beta and TNF-alpha following lipopolysaccharide (LPS), heat-killed Staphylococcus epidermidis or concanavalin A stimulation. Moreover, a disproportionate amount of the overall increase in IL 1 (alpha and beta) was secreted in contrast to the amount which remained cell associated, an effect unrelated to cell damage or leakage as tebufelone had no effect on either lactate dehydrogenase release by PBMC, or mitochondrial dehydrogenases of adherent monocytes as detected by enzymatic cleavage of the substrate 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide. There was no inverse correlation between the changes in prostaglandin (PG)E2 levels and TNF-alpha or IL 1 beta synthesis, and when PG formation was maximally inhibited by preincubating the cells in indomethacin, tebufelone, added 1 h before the stimulus, continued to enhance the synthesis of IL 1 beta although not that of TNF-alpha. The addition of the CO/5-LO inhibitor 2 h after LPS stimulation, however, did not interfere with IL 1 beta synthesis, suggesting that tebufelone interacts with an early event(s) in the activation of PBMC. For IL 1 beta and TNF-alpha, basal and stimulated (4 h post LPS) mRNA levels were not increased by tebufelone, despite a concomitant increase in the synthesis of IL 1 beta. In conclusion, we have demonstrated that tebufelone enhances IL 1 (alpha and beta) and TNF-alpha synthesis at concentrations which suppress leukotriene formation. These findings argue against a role of 5-LO products as necessary intermediates of IL 1 (alpha and beta) and TNF-alpha synthesis.
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PMID:Transcription, translation and secretion of interleukin 1 and tumor necrosis factor: effects of tebufelone, a dual cyclooxygenase/5-lipoxygenase inhibitor. 184 74

Despite continuous exposure to gut-derived endotoxin (lipopolysaccharide) under normal conditions, Kupffer cells (KC) fail to generate detrimental cytokine responses. KC function within a unique microenvironment in which high hepatic arginase activities (25 times greater than those activities in the kidney) result in negligible local L-arginine levels. To evaluate the relevance of this profound arginine deficiency on the physiologic function of KC, the kinetics of tumor necrosis factor (TNF-alpha) production and autoregulatory eicosanoid prostaglandin E2 (PGE2) production were compared in lipopolysaccharide-stimulated KC cultured with (1200 mumol/L) and without (10 mumol/L) L-arginine media. In (+)arginine culture the KC TNF-alpha production peaked early before decreasing as PGE2 production increased. In (-)arginine culture, however, KC TNF-alpha production was significantly (p less than 0.01) reduced, whereas PGE2 production was amplified (p less than 0.01). When cyclooxygenase blockade with indomethacin completely prevented KC production of PGE2 in (-)arginine culture, TNF-alpha production was upregulated (p less than 0.001 vs (-)arginine; p not significant vs (+)arginine). These arginine-specific depression of TNF-alpha responses appeared unique to KC because both TNF-alpha and PGE2 levels increased when peritoneal, pleural, and alveolar macrophages were stimulated by lipopolysaccharide in (-)arginine medium. This PGE2-dependent autoregulation of potentially harmful lipopolysaccharide-induced TNF-alpha responses may reflect an evolutionary adaptation by KC to their local hepatic environment and strategic anatomic position in the portal circuit, which optimally removes endotoxin and naturally protects the host.
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PMID:A biologic basis for limited Kupffer cell reactivity to portal-derived endotoxin. 185 31

To determine whether endotoxemia and release of tumor necrosis factor (TNF-alpha) and/or interleukin 1 alpha (IL-1 alpha) are involved in the pathogenesis of heatstroke, 17 adult patients with a mean rectal temperature of 42.1 +/- 0.2 degrees C were studied. Blood samples were taken on admission and after cooling was completed. TNF-alpha and IL-1 alpha levels were measured by enzyme-linked immunosorbent assay, and lipopolysaccharide (LPS) content was measured by the chromogenic substrate modification of the Limulus amebocyte lysate. TNF-alpha, IL-1 alpha, and LPS were elevated in all patients [199 +/- 25 (SE) pg/ml, 480.5 +/- 68.3 pg/ml, and 8.60 +/- 1.19 ng/ml, respectively, compared with normal control values of 31.4 +/- 8.4 pg/ml, 53.7 +/- 5.32 pg/ml, and less than 9 pg/ml]. There was no significant correlation between temperature and the circulating concentration of TNF-alpha, IL-1 alpha, and LPS. Postcooling TNF-alpha, IL-1 alpha, and LPS concentrations were significantly decreased but still above normal control values. The findings suggest that these mediators may have a role in the pathogenesis of heatstroke that could change the strategy of management.
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PMID:Endotoxemia and release of tumor necrosis factor and interleukin 1 alpha in acute heatstroke. 188 59


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