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)

Combined effects of chemically synthesized lipid A analogs, the compound A-171 (acylglucosamine-4-phosphate with (R)-3-hydroxytetradecanoyl and (R)-3-hydroxytetradecanoyloxy]tetradecanoyl group at the C-2 and C-3 positions), or the compound A-172 (with (R)-3-hydroxytetradecanoyloxy]tetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl group at the C-2 and C-3 positions), and muramyl dipeptide (MDP) on antitumor activity against Meth A fibrosarcoma, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated intradermally into BALB/c mice on day 0, compound A-172 and/or MDP were administered intravenously (i.v.) on day 7. Although the antitumor activity by single i.v. injection of A-172 (50 micrograms/mouse) with MDP (10 micrograms) was weaker than that of 50 micrograms of synthetic lipid A analogs (506), or 10 micrograms of bacterial lipopolysaccharide (LPS) with MDP, A-172 alone and with MDP exhibited tumor inhibition rates of 49.0 and 70.6%, respectively. When A-171 (50 micrograms) with MDP (10 micrograms) was administered i.v. twice (days 7 and 10) into mice inoculated Meth A fibrosarcoma, two of five mice caused complete tumor regression. Furthermore, L929 cell lysis by the combination of A-171, A-172 with MDP was higher than that by the analogs or MDP alone, suggesting that the lipid A analogs of monosaccharide type as well as LPS are able to enhance the production of tumor necrosis factor in the presence of MDP.
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PMID:Combined effects of synthetic lipid A analogs and muramyl dipeptide on antitumor activity against Meth A fibrosarcoma in mice. 178 74

In vivo stimulation of pulmonary alveolar macrophages (PAMs) may enhance tumor cell cytotoxicity. A model using aerosolized gamma-interferon (gamma-IFN) and lipopolysaccharide (LPS) was developed to induce enhanced PAM activation in vivo in C57BL/6 mice. Mice received four doses of aerosol (2 doses/day) consisting of gamma-IFN (10(4) microU/mouse) and LPS (100 micrograms/mouse). Other groups received either gamma-IFN alone, LPS alone, or saline (control). Cells were harvested by bronchoalveolar lavage. Macrophage cell count demonstrated an increase in macrophage recruitment in the gamma-IFN and LPS group. PAMs were evaluated for in vitro cytotoxicity against B16-F10 melanoma cells. Treatment groups demonstrated enhanced cytotoxicity over controls, and the combination (gamma-IFN plus LPS) was significantly better in cell killing than either treatment modality alone (p less than or equal to 0.02). Activated PAMs selectively killed tumor cells, but did not kill the 3T3 fibroblast cell line. Peritoneal macrophages from mice treated by inhalational gamma-IFN + LPS were enhanced (indicating a systemic effect), but not to the same extent as PAMs. These studies suggest that inhalation of gamma-IFN + LPS can selectively enhance in vivo cytotoxicity of murine PAMs. This may potentially be applicable to human tumor management.
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PMID:Aerosolized gamma-interferon and lipopolysaccharide enhances cytotoxicity of murine pulmonary alveolar macrophages. 190 97

The lipopolysaccharides, lipopolysaccharide-protein complexes and their lipids A, isolated from Shigella dysenteriae 1, exhibited lethal toxicity (LD50 300-400 micrograms per mouse), pyrogenicity (0.01-1.0 microgram), activity in the Limulus test (10(-3)-10(-12) mg ml-1) and produced a positive local Shwartzman reaction. It was found that these substances bound to Al(OH)3 were capable of successfully protecting mice from challenge with both homologous and heterologous infections (up to 90% of mice survived a challenge with LD100), whereas immunization with substances with no biological carrier exhibited very low or zero protective effects. Furthermore, the positive cross-reactivity of lipids A in the agar immunodiffusion test confirms the wide applicability for vaccination purposes.
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PMID:New trends in the use of Al(OH)3-conjugated endotoxins and their subunits from the S- and R-forms of Shigella dysenteriae serovar 1 for model vaccination purposes. 190 47

We have developed an adjuvant formulation (SAF) consisting of a synthetic muramyl dipeptide analogue (N-acetylmuramyl-L-threonyl-D-isoglutamine) in a squalane-Pluronic polymer emulsion. Used with a variety of antigens SAF elicits cell-mediated immunity and antibodies of protective isotypes (IgG2a in the mouse). SAF augments responses to influenza virus haemagglutinin and hepatitis B virus surface antigen. Vaccines using SAF have protected guinea pigs against genital herpes simplex virus infections and subhuman primates against Epstein-Barr virus and simian immunodeficiency virus infections. Properties of SAF are compared with those of other adjuvants, including lipopolysaccharide analogs, ISCOMs and liposomes.
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PMID:Adjuvant formulations and their mode of action. 196 59

Metallothionein (MT), a low molecular-weight, cysteine-rich, metal-binding protein, is induced by many environmental factors and a variety of stimuli. Bacterial endotoxin (lipopolysaccharide, LPS) injection is experimentally used to produce acute stress and is an effective inducer of hepatic MT. However, the mechanism of LPS induction of MT is not known. In the present studies, we used two substrains of mice, differing in their production of cytokines after LPS administration, to test the hypothesis that MT induction by LPS is mediated through cytokines. Normal (C3Heb/FeJ) and low cytokine-producing (C3H/HeJ) mice were given various doses of LPS, interleukin-1 (IL-1), interleukin-6 (IL-6), or tumor necrosis factor (TNF), and hepatic MT was determined 24 hr later by the Cd/hemoglobin assay. The low-cytokine-producing mice were much less responsive to the induction of MT by LPS (50 vs 150 micrograms MT/g liver after 1.0 mg LPS/kg, ip) than the normal mice, but were equally responsive to the induction of MT by IL-1 (0.03-1.0 microgram/mouse). IL-6 (0.5-5.0 micrograms/mouse), and TNF (0.005-0.5 microgram/mouse). All the cytokines produced a dose-dependent increase of hepatic MT levels in these two murine substrains (up to five- to sevenfold over controls). In conclusion, these data suggest that LPS induction of MT may be mediated through cytokines.
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PMID:Endotoxin induction of hepatic metallothionein is mediated through cytokines. 206 24

The ability of recombinant murine (rMu) interferon (IFN)-gamma to activate anti-Salmonella-activity in normal mice and beige mutant (bg/bg) mice with Chediak-Higashi syndrome (CHS) was examined. Previous intraperitoneal (i.p.) injection of rMuIFN-gamma (10(4) U per mouse) significantly hindered the bacterial growth in the peritoneal cavities, spleens and livers of the mice after the i.p. infection with Salmonella enteritidis No. 11 strain. It was also effective on the beige mice that have phagocytic cells with a genetically impaired bactericidal function, suggesting that IFN-gamma activates the pathway irrelevant to the beige mutation. The effect was the maximum, when IFN-gamma was given 6 h before the challenge. The effect seemed to be due to the augmentation of bactericidal capacity rather than the prevention of systemic spread of bacteria. Recombinant human IFN-alphaA/D (10(2)-10(6) U per mouse), which produced effects identical to those of murine IFN-beta, did not show such a bactericidal effect. Bactericidal activity enhancement was also seen in mice that had been injected with a small amount of rMuIFN-gamma (10(2) U) and bacterial lipopolysaccharide (LPS) (10 ng) together at 6 h before the challenge, although the IFN-gamma or LPS alone at these doses produced very little if any effect. Bactericidal effect enhancement was seen in mice that had been injected with IFN-gamma at 6 h and LPS at 3 h before the challenge, while it could be hardly seen in mice injected with them in a reversed order.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of murine recombinant interferon-gamma in the protection of mice against Salmonella. 210 15

Mice lethally infected with the C56 strain of Toxoplasma gondii and treated with purified recombinant murine tumour necrosis factor (TNF, 1 microgram/day/mouse for 8 days), recombinant human interleukin-1 (IL-1 alpha or IL-1 beta, 100 ng/day/mouse for 5 days) or a single dose of a combination of TNF (1 microgram/mouse) and IL-1 alpha or IL-1 beta (100 ng/mouse) were significantly protected against death (P less than 0.05-0.001, as compared with untreated infected controls). Mice infected with 100,000 tachyzoites of the highly virulent RH strain of T. gondii released serum TNF in relation to the time after infection and were primed to secrete an enhanced level of serum TNF upon stimulation with bacterial lipopolysaccharide (LPS). In vitro studies showed that interferon-gamma (IFN-gamma) increased the antimicrobial activity of murine peritoneal macrophages whereas TNF, IL-1 alpha and IL-1 beta did not. TNF, however, synergized with the anti-toxoplasmic effect provided by IFN-gamma and this activity was blocked by anti-TNF antibodies. IFN-gamma induced the production of TNF and the anti-toxoplasmic effect provided by IFN-gamma seemed to be dependent partly on the production of TNF. We conclude that TNF and IL-1 may play a significant role in modulating the host's immune defence against T. gondii infection.
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PMID:Role of TNF and IL-1 in infections with Toxoplasma gondii. 210 44

Antitumor activity, mitogenicity, and lethal toxicity of chemically synthesized lipid A analogs, acylglucosamine-4- or -6-phosphate with the alpha, beta-hydroxyacyl, acyloxyacyl, or hydroxyacyloxacyl groups at the C-2 and C-3 positions, were examined. Meth A fibrosarcoma cells (5 X 10(5)) were inoculated subcutaneously into BALB/c mice on day 0, and six compounds (50 micrograms/mouse) were administered intravenously on days 7 and 9. Although the antitumor activity of these compounds was weaker than that of natural lipopolysaccharide (LPS) or the synthetic lipid A analog (506) of Escherichia sp type, all groups exhibited tumor inhibition rates of 40% to 50% and delayed tumor growth. Six compounds, with the exception of compound A-173 (with the hydroxytetranoyl group at the C-2 and C-3 positions), were capable of increasing the incorporation of [3H]thymidine into cultured splenocytes of C57BL/6 mice, and caused lethal toxicity in C57BL/6 mice sensitized with galactosamine. However, these compounds had lower toxicity than bacterial LPS (about 500- to 1,000-fold). Compounds A-172 and A-174, which have the same structure except for the C-4 or C-6 position of the phosphate group, exerted similar antitumor activity, mitogenicity, and lethality. The results discussed above indicate that the biologic activity of these compounds correlates with the carbon number of fatty acid but is not affected by the different location of the phosphate group. Furthermore, it seems that the difference between the alpha, beta-hydroxy position of fatty acid and the R or S configuration does not alter the biologic effects.
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PMID:Antitumor activity against Meth A fibrosarcoma and biologic activities of synthetic monosaccharide analogs of lipid A in mice. 236 54

We measured the frequency of sister chromatid exchanges (SCEs) in human and mouse peripheral lymphocytes using doses of bromodeoxyuridine (BrdU) ranging from 30 nM to 100 microM (human) and from 10 nM to 10 microM (mouse). Heparinized peripheral blood was obtained from five healthy nonsmokers and from six C57B1/6 male mice. The blood was stimulated with PHA (human) or lipopolysaccharide (LPS, mouse) and grown for the first of two cell cycles in BrdU. Metaphase chromosomes were denatured and exposed to a monoclonal antibody reactive to single-stranded DNA containing BrdU. A second antibody was used to label the first antibody with fluorescein, and propidium iodide was used as a counterstain. Second-division metaphases were thus differentially stained red to indicate DNA content and yellow-green to indicate the presence of BrdU. The results indicate that the baseline SCE frequency in human and mouse peripheral lymphocytes is 3.6 and 2.4 SCEs per cell per generation, and that in the human these frequencies are invariant at the lowest BrdU levels. This suggests that SCEs are an integral part of DNA replication, even in the absence of agents known to induce SCEs. The distribution of SCEs per chromosome was analyzed and found to be Poisson-distributed in all 24 murine cultures and in 25 of 36 human cultures. The distribution of SCEs per chromosome may be due to either species-specific chromosome packaging or to karyotypic differences between the species.
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PMID:Determination of the baseline sister chromatid exchange frequency in human and mouse peripheral lymphocytes using monoclonal antibodies and very low doses of bromodeoxyuridine. 243 Jul 61

The priming effect of endogenous biological response modifiers (BRMs), interferons (IFNs), and interleukin-2 (IL2), and the triggering effect of BRMs of bacterial origin, OK-432 and Corynebacterium parvum, on endogenous production of the tumor necrosis factor (TNF) were investigated in mice. TNF activity in serum was measured by in vitro cytotoxicity assay with L-929 cells as a target. The i.v. injection of OK-432 (3KE per mouse) triggered TNF maximally (mean value: 30 U/ml) after 2 h, with a similar time course to that of triggering by lipopolysaccharide. The priming activities of IFNs and IL2 were examined in the system of TNF-triggering by OK-432. The i.v. injection of recombinant IFN-gamma (rIFN-gamma, 10(4) U per mouse) increased TNF production to 790 U/ml; this priming effect was observed just after its injection, was maximal after 2 to 6 h, and disappeared after 24 h. Other types of interferon, rIFN-alpha A/D(Bgl) (2 X 10(5) U per mouse), rIFN-beta (10(6) U per mouse), and natural IFN-alpha/beta (10(6) U per mouse) showed maximal priming activity 6 h after their injection (200 to 800 U/ml) but no effect just after their injection. Recombinant IL2 (10(6) U per mouse) had priming activity that showed a similar time course to that of interferons other than IFN-gamma (a maximal TNF production: 100 U/ml). The i.v. injection of C. parvum, like OK-432, triggered TNF production at doses of 0.06 and 0.3 mg per mouse 2 h after its injection and the triggered TNF activity was enhanced by rIFN-gamma. These findings suggest that combinations of the above endogenous BRMs as priming agents and OK-432 or C. parvum as a triggering agent could induce endogenous production of TNF even in human cancer patients. In fact, combined administration of rIFN-gamma and OK-432 produced TNF in human cancer patients. The advantage of this method for treatment of human cancer patients is discussed.
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PMID:Endogenous production of tumor necrosis factor in normal mice and human cancer patients by interferons and other cytokines combined with biological response modifiers of bacterial origin. 244 26


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