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)

The xanthine derivative A 802715 (1-(5-hydroxy-5-methyl)hexyl-3-methyl-7- propyl-xanthine, Hoechst AG) caused dose-dependent protection against lipopolysaccharide (LPS)-induced lethal shock in mice. In animals which had received the compound, the LPS-induced increase of serum tumor necrosis factor (TNF alpha) levels was not significantly affected. Protection against LPS-induced lethality was observed not only when A 802715 was given 1 hr before or simultaneously with LPS but also when administered 1 hr after LPS challenge. Administration of 200 mg/kg of the compound 1 hr before challenge also fully protected against lethal shock induced by intravenous administration of recombinant murine TNF alpha. It is concluded that A 802715 counteracts TNF alpha toxicity and that the drug bears the potential of therapeutic intervention in septic shock.
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PMID:A novel xanthine derivative counteracting in vivo tumor necrosis factor alpha toxicity in mice. 144 84

SK&F 105809 is a structurally novel dual inhibitor of lipoxygenase and cyclooxygenase-mediated arachidonic acid (AA) metabolism, which has demonstrated antiinflammatory activity in rodent models of inflammation. In addition, the active metabolite of this compound, SK&F 105561, has been shown in vitro to inhibit the production of the inflammatory cytokine interleukin-1 (IL-1) in human monocytes stimulated with lipopolysaccharide (LPS). We report here that in vitro SK&F 105561 also blocks the production of tumor necrosis factor (TNF) from human monocytes (IC50 0.8-3 microM). Furthermore, in a murine model of endotoxin shock in which animals are injected with LPS in combination with D-galactosamine (D-gal), SK&F 105809 (10, 30, and 100 mg/kg p.o.), delivered 30 min prior to LPS/D-gal, caused a dramatic reduction in serum TNF (40-90%) and protected the animals from the lethal effects of this treatment. Similar results were obtained in a second model of endotoxin shock in which mice were sensitized with Propionibacterium acnes 10 days prior to LPS injection. In this system 100-fold higher levels of serum TNF are elicited than with the LPS/D-gal model. Treatment with SK&F 105809 (30 and 100 mg/kg p.o.) delivered 30 min prior to LPS resulted in 90-100% inhibition of serum TNF. Protection from the lethal effects of LPS was observed at these doses in the P. acnes/LPS model.
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PMID:Beneficial effects of SK&F 105809, a novel cytokine-suppressive agent, in murine models of endotoxin shock. 144 88

The immunomodulatory hormone 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to suppress T-cell proliferation and interleukin-2 synthesis as well as B-cell immunoglobulin synthesis, while stimulating many macrophage functions. We have previously shown increased synthesis of interleukin-1 beta in lipopolysaccharide (LPS)-stimulated U937 cells after pretreatment with 10 nmol/L 1,25-(OH)2D3. We now show that 1,25-(OH)2D3 also primes the increase in U937 cell tumor necrosis factor (TNF)-alpha-accumulated mRNA after activation with LPS; 50% effective concentration (EC50) for the LPS-induced expression of TNF-alpha mRNA was decreased by two orders of magnitude after incubation with 10 nmol/L 1,25-(OH)2D3. Pretreatment of U937 cells with 10 nmol/L 1,25-(OH)2D3 also increased subsequent LPS-induced TNF-alpha mRNA expression by twofold and cell-associated TNF protein levels by more than ninefold. This potentiation was steroid-specific for 1,25-(OH)2D3 because dexamethasone inhibited TNF-alpha mRNA. The potentiation required prior exposure to 1,25-(OH)2D3 for more than 6 hours and was clearly seen after 12 hours. The finding that the sensitivity of the U937 cell monokine response to LPS was dramatically increased by 1,25-(OH)2D3 and the delayed effect on the LPS-stimulated TNF-alpha gene transcript levels indicated that 1,25-(OH)2D3 may be altering the expression of a protein(s) in the U937 cell LPS-signal transduction pathway. In fact, 1,25-(OH)2D3 induced expression of the mRNA for CD14, the high affinity, cell-surface glycoprotein receptor for LPS, which could account for the enhancement of LPS-stimulated monokine gene expression by 1,25-(OH)2D3. Thus, local monokine gene expression may be regulated by both the amount and the temporal entry of the vitamin D hormone and activator(s) into the inflammatory microenvironment.
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PMID:Potentiation of lipopolysaccharide-induced tumor necrosis factor-alpha expression by 1,25-dihydroxyvitamin D3. 145 Apr 7

Serum levels of various cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL1-beta), and interleukin 2 (IL2), and of soluble IL2 receptors (sIL2R) were determined in 30 patients with definite systemic sclerosis (SSc). Spontaneous and lipopolysaccharide-or mitogen-induced production of the cytokines, TNF-alpha, IL1-beta, and IFN-gamma, by peripheral blood mononuclear cells (PBMNC) of these SSc patients was measured by immunoassays. The patients were divided into three groups: 12 with limited cutaneous disease (lcSSc), 7 with diffuse cutaneous disease (dcSSc) < 3 years duration, and 11 with dcSSc > 3 years duration. None were treated with cytotoxic drugs or biologic response modifiers. Sera of patients with SSc had elevated sIL2R levels, and only low levels of IL2 (1-2 U/ml) were detected in 10/29 sera tested. Spontaneous production of TNF-alpha and IL1-beta by PBMNC of patients with SSc (829 pg/ml +/- 215 SEM and 728 pg/ml +/- 186, respectively) was significantly higher than that by normal PBMNC obtained from 30 volunteers (25 +/- 10 and 34 +/- 6 pg/ml, respectively) and tested at the same time as patients' PBMNC. The largest increases in spontaneous release of TNF-alpha or IL1-beta were seen in patients with early dcSSc. No significant difference in spontaneous IFN-gamma production by patient or control PBMNC was detected. On the other hand, the mean level of mitogen-induced IFN-gamma production by PBMNC was significantly depressed in patients with SSc (103 U/ml +/- 18 vs 255 +/- 33 U/ml in controls). In vitro-induced production of TNF-alpha or IL1-beta by patients' PBMNC was comparable to that of normal PBMNC. These data indicate that in vivo-activated PBMNC of patients with SSc spontaneously secrete excessive amounts of fibrogenic cytokines, which are involved in modulation of connective tissue synthesis.
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PMID:Cytokine production and serum levels in systemic sclerosis. 145 30

The effect of HIV infection on the production of tumor necrosis factor-alpha (TNF-alpha) was examined in patients with advanced human immunodeficiency virus (HIV) infection in the absence of AIDS-related secondary infections. Serum TNF-alpha and TNF-alpha production in vitro were measured by enzyme-linked immunosorbent assay in 26 male homosexuals with CDC stage IV HIV infection without active AIDS-related secondary infections. In vitro TNF-alpha production was assayed from cultured peripheral blood mononuclear cells (PBMs) or whole blood cultures under conditions for minimising endotoxin contamination. PBMs and whole blood were cultured with and without lipopolysaccharide (LPS). Results were compared with those for 13 HIV-seronegative age- and sex-matched controls. Serum TNF-alpha concentrations were 5 +/- 16 pg/ml in HIV-infected patients and 12 +/- 17 pg/ml in controls. TNF-alpha levels in unstimulated cultures of PBMs obtained from patients were 426 +/- 511 pg/ml and 456 +/- 428 pg/ml in control cultures. There was no difference between groups in the maximal responses of cultured PBMs to stimulation with LPS (2,229 +/- 1,593 pg/ml vs. 2,504 +/- 961 pg/ml). TNF-alpha levels from unstimulated and LPS-stimulated whole blood cultures were not significantly different after adjusting for the number of cultured monocytes (2,038 +/- 1,469 pg/ml vs. 1,511 +/- 488 pg/ml). In 10 patients (38%) the TNF-alpha levels from stimulated whole blood cultures were greater than the 95% confidence interval of the control group. TNF-alpha levels in patients were not significantly altered by antiretroviral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor-alpha in advanced HIV infection in the absence of AIDS-related secondary infections. 145 35

Culture supernatants from lipopolysaccharide (LPS)-treated murine microglial cells were found to markedly induce the expression of human immunodeficiency virus (HIV)-1 in the chronically infected human promonocytic cell line U1 as detected by measurements of HIV-1 p24 antigen release into U1 culture supernatants. Antibody to tumor necrosis factor (TNF)-alpha had an inhibitory effect on the induction of virus by microglial cell supernatants. Also, treatment of microglia with pentoxifylline, an inhibitor of TNF-alpha production, resulted in suppressed amounts of TNF in the supernatants of LPS-treated microglia and in a reduced stimulatory capacity of these supernatants on HIV-1 expression in U1 cells. These findings support the concept that TNF-alpha production by glial cells plays a pathogenetic role in HIV-1-associated brain disease by promoting the expression of the virus in infected cells.
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PMID:Microglial cell upregulation of HIV-1 expression in the chronically infected promonocytic cell line U1: the role of tumor necrosis factor-alpha. 146 95

The ability of orally administered Deodan, a product from the cell wall of Lactobacillus bulgaricus strain "I. Bogdanov patent strain tumoronecroticance B51" ATCC #21815, shortly called "LB51", to induce endogenous tumor necrosis factor-alpha (TNF alpha) production in normal mice was evaluated. The priming and triggering activities of the preparation were investigated in combination with lipopolysaccharide (LPS) and live BCG vaccine. Deodan was applied at a dose of 150 mg/kg and various treatment schedules were employed. The serum levels of TNF alpha in treated mice were quantified by ELISA. Oral administration of Deodan at a dose of 150 mg/kg for 1, 3, 10 or 20 consecutive days only enhanced serum TNF alpha levels in treated mice. Maximal TNF alpha levels were reached 6 h after the last application of Deodan. Deodan was effective in priming TNF alpha in mice triggered intravenously (i.v.) with LPS. Deodan triggered the production of TNF alpha in BCG-primed mice. The preparation, however, was not an effective trigger of mice primed intradermally (i.d.) with 1 microgram/mouse LPS. These findings suggest that Deodan is both a primer and trigger of endogenous TNF alpha. The advantages of treatment of neoplastic disease with agents which induce endogenous TNF alpha is discussed.
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PMID:Endogenous production of tumor necrosis factor in normal mice orally treated with Deodan--a preparation from Lactobacillus bulgaricus "LB51". 146 68

The combined effects of the synthetic glucosaminylmuramyl dipeptide (GMDP) on the antitumor activity of chemically synthesized lipid A analogs, compound A-103 (glucosamine-4-phosphate with (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), Escherichia coli-type lipid A (506), Salmonella typhimurium LT-2 lipopolysaccharide (LPS) against Meth A fibrosarcoma in mice were examined. Meth A fibrosarcoma cells (5 x 10(5) were inoculated intradermally into BALB/c mice on day 0, and compound A-103 and/or GMDP was administered intravenously (i.v.) on days 7 and 9. Two i.v. injections of A-103 (50 micrograms) alone or GMDP (10 micrograms) alone induced 42.8 or 51.8% inhibition of the rate of tumor growth, however, A-103 (100 micrograms) with GMDP (10 micrograms) exhibited a high 68.7% inhibition rate 19 days after tumor inoculation. The inhibition of the tumor growth rate by the combination A-103 (100 micrograms) or 506 (50 micrograms) with GMDP (10 micrograms) was stronger than that of A-103 or 506 with MDP (10 micrograms). The combination of LPS (1 or 10 micrograms) with GMDP (10 micrograms) exhibited a higher inhibition rate than that of LPS with MDP, and three or four tumor-free mice out of five mice were observed, suggesting that the combined effect of GMDP is more potent than that of MDP. With the addition of GMDP, A-103 did not enhance the production of tumor necrosis factor (TNF) on the basis of L929 cell lysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Combined effects of synthetic lipid A analogs or bacterial lipopolysaccharide with glucosaminylmuramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice. 146 73

Macrophages contribute to the systemic inflammatory response that characterizes the sepsis syndrome through the production of inflammatory cytokines such as tumor necrosis factor (TNF). Liposome-encapsulated hemoglobin (LEH), a potential red cell substitute, is cleared by fixed tissue macrophages. In these studies, in vitro incubation of alveolar macrophages with stored LEH was shown to inhibit the expression of TNF induced by endotoxin (lipopolysaccharide, LPS) stimulation. This effect was dependent on LEH dose but independent of the period of exposure to the LEH. Despite inhibition of TNF expression, Northern blot analysis of total cellular RNA from LPS-stimulated macrophages revealed accumulations of TNF-specific transcripts in cells treated with or without LEH. Thus the mechanism of LEH inhibition of TNF expression appears to involve a posttranscriptional event. Although these results suggest a potential advantage of resuscitation with LEH when sepsis complicates hemorrhagic shock, immunomodulation in vivo remains to be defined.
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PMID:Liposome-encapsulated hemoglobin inhibits tumor necrosis factor release from rabbit alveolar macrophages by a posttranscriptional mechanism. 146 39

The interleukin-6-(IL-6)-alpha dependent B-cell heterohybridomas were obtained by the fusion of X65.Ag8.653 cells with spleen cells from August rats immunized with lipopolysaccharide E. coli. One of these hybridomas (D6C8) was found to be most dependent on IL-6 for its surviving and growth. Human recombinant IL-1 beta and tumor necrosis factor-alpha could not induce the in vitro growth of this cell line. Presence of elevated level of IL-6 was demonstrated in the sera of patients with rheumatoid arthritis. A specific and sensitive detection of the IL-6 activity in test samples makes it possible to study the presence and role of IL-6 in various immunological disorders.
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PMID:[The production and characteristics of an interleukin-6-dependent hybridoma]. 146 86


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