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 murine pre-B cell line 70Z/3 responds to lipopolysaccharide (LPS), interleukin-1 (IL-1) or interferon-gamma (IGN gamma) by kappa gene transcription and expression of surface IgM (sIg). We found that muramyl dipeptide (MDP), a synthetic immunoadjuvant analog of a bacterial membrane structure, produced a weak increase in the number of sIg-positive 70Z/3 cells as measured by immunofluorescence staining. This number was significantly increased after exposure to MDP. Moreover, when MDP was used in combination with LPS, IL-1 or IFN gamma, an enhancement of sIg expression was observed showing an early influence of MDP in the presence of a second stimulant. Unexpectedly, two adjuvant-active analogs of MDP did not share its capacity to stimulate differentiation of the cell line when used alone or associated with other agents, indicating that adjuvanticity of MDP was not the only requirement. Two other products of bacterial origin, a Staphylococcus aureus cell extract (SAC) and the Toxic Shock Syndrome Toxin TSST-1 could neither enhance the kappa gene expression in 70Z/3 cells nor increase the MDP effect. The stimulating effect displayed by MDP could by related to NF-kappa B activation.
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PMID:Differential regulation of surface immunoglobulin expression by various muramyl dipeptides in a murine pre-B cell line. 755 76

In a number of mammalian cell types, pteridine biosynthesis from guanosine 5'-triphosphate and formation of nitric oxide from L-arginine are induced by gamma interferon (IFN-gamma) and bacterial lipopolysaccharide (LPS). We assessed the possibility of using such metabolic alterations for the in vitro detection of pyrogens. Products from gram-negative and gram-positive bacteria and related synthetic compounds were tested for their potential to induce either of these pathways. Stimulation of pteridine biosynthesis was monitored as the formation of neopterin in the human myelomonocytic cell line THP-1. The formation of nitric oxide was determined as nitrite in murine J774A.1 macrophage cultures. The substances tested included toxic and detoxified parts of LPS and lipid A from Escherichia coli, Salmonella typhimurium, Salmonella minnesota, and Klebsiella pneumoniae as well as lipoteichoic acid and toxic shock syndrome toxin 1 from Staphylococcus aureus. Furthermore, two cell wall compounds from Mycobacterium tuberculosis, trehalose 6,6'-dimycolate and N-acetylmuramyl-L-alanyl-D-isoglutamine, which are active components of Freund's adjuvant, were used. When applied as a single stimulus, only the whole LPS molecule potently stimulated neopterin or nitrite formation. Lipid A and products from gram-positive bacteria were weakly active. For neopterin formation, lipid A required the presence of fetal calf serum. Besides detoxified LPS and independently from the presence of serum, all bacterial compounds tested strongly increased the effects mediated by IFN-gamma. Our results show that bacterial pyrogens can be detected by monitoring the formation of neopterin or nitrite. This may provide a basis for the development of an in vitro assay for the detection of pyrogenic contamination with the aim of replacing the currently used animal test.
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PMID:Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines. 766 77

Zinc is known to be greatly involved in the regulation of immune functions. Pharmacological zinc supplementation, leading to serum zinc concentrations of more than 0.025 mM, has often been suggested to improve immune responses. However, the exact influence of elevated zinc level on immune functions has not yet been investigated. We found that zinc level selectively enhances cytokine induction by lipopolysaccharide (LPS) in a concentration-dependent fashion: as little as 0.0125 mM supplemental zinc led to nearly 50% elevated interleukin-1 beta (IL-1 beta) levels both in polymorphonuclear cells (PBMC) and whole-blood cultures. The secretion of interferon-gamma (IFN-gamma) could be increased more than 10-fold by 0.1 mM zinc. This could not be observed during stimulation with phytohaemagglutin (PHA). In contrast, zinc levels concentration-dependently down-regulated monocyte activation caused by the superantigens, staphylococcal enterotoxins A and E (SEA, SEE, more than 90% down-regulation by 0.1 mM zinc), the Mycoplasma arthritidis-derived superantigen (MAS), but not toxic shock syndrome toxin-1 (TSST-1), while T-cell response remained unaffected. This was not the result of chemical degradation of the superantigens. We assume that zinc concentration regulates interactions between SEA, SEE and MAS, but not TSST-1 and their major histocompatibility complex (MHC) class II-binding sites. Our data demonstrate that zinc levels control the secretion of IFN-gamma and monokines after both LPS and superantigen challenge within a clinically relevant range of concentrations. This reveals new perspectives and indications for zinc supplementation and also indicates potential risks of therapeutic application of zinc.
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PMID:Zinc regulates cytokine induction by superantigens and lipopolysaccharide. 775 Oct 4

Measurement of cytokine secretion in vitro is usually performed in culture medium supplemented with human serum. We compared the secretion of interferon-gamma and interleukin-1 beta as a parameter for lymphocyte and monocyte activation in RPMI 1640 medium supplemented with fetal calf or autologous serum in serum-free medium and protein-free medium. Four different stimulatory mechanisms were tested: phytohemagglutinin, toxic shock syndrome toxin-1 (TSST-1), lipopolysaccharide (LPS), and zinc ions. We found that the optimal stimulatory zinc concentration depended on the total protein content of the medium, whereas the monokine levels were dependent on the concentration of transport proteins such as transferrin. Monokine induction by LPS or TSST-1 were each influenced by the protein and serum composition in a specific manner. Our results show that the differing mechanisms of cytokine induction are influenced by the medium and serum composition in a diverse but specific manner. Serum- or protein-free medium are especially suitable after superantigen challenge when LPS activity needs to be ruled out or after activation by agents with only a weak stimulatory capacity.
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PMID:Influence of serum on zinc, toxic shock syndrome toxin-1, and lipopolysaccharide-induced production of IFN-gamma and IL-1 beta by human mononuclear cells. 779 Jul 74

Pretreatment of animals with the adjuvant muramyl dipeptide enhances both the production of circulating tumor necrosis factor and the sensitivity to the lethal effect of a lipopolysaccharide (LPS) challenge. The present study examined the capacity of various adjuvant muramyl dipeptide derivatives to potentiate responsiveness to LPS administration. Cytokine levels in serum were determined at various time intervals after LPS administration by bioassays and immunoassays; the cytokines examined were tumor necrosis factor, interleukin-1, interleukin-6, and gamma interferon. The time course of cytokine response was not modified by the pretreatment, but most of the levels were strongly enhanced. However, of the four compounds which were found to be potent priming agents, only two caused an increased sensitivity to LPS lethality, showing that elevated titers of cytokines in serum were not correlated with host sensitization. Interestingly, previous studies have shown that these two compounds also display neurobiological properties, implying a possible role of the central nervous system in LPS lethality. However, two hydrophilic derivatives with low activity as priming agents were capable of decreasing the toxicity of LPS when given after the challenge in galactosamine-sensitized mice. These results illustrate the diversity of responses elicited by immunological priming. They raise unanswered questions on the importance of endogenous mediators in the pathophysiological alterations during toxic shock.
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PMID:Selective modulation of lipopolysaccharide-induced death and cytokine production by various muramyl peptides. 780 45

Zinc is essential for immunologic function; therefore, it has been postulated that elevated serum levels of zinc might lead to improved immune responses. However, it is not known whether or how serum zinc levels contribute to a clinically relevant mechanism of immunologic activation. In our studies with human peripheral blood mononuclear cells and whole blood, the zinc level selectively enhanced the biologic activity of endotoxin. The combination of nonstimulatory doses of lipopolysaccharide (LPS) and nonstimulatory concentrations of zinc led to the secretion of large amounts of interleukin (IL)-1 beta. In contrast, zinc levels specifically down-regulated monocyte activation caused by some superantigens, staphylococcal enterotoxin A and E and Mycoplasma arthritidis--derived superantigen, but not toxic shock syndrome toxin-1. This demonstrates that zinc levels control IL-1 beta secretion after both LPS and superantigen challenge within a clinically relevant range of concentrations. Our data suggest that the indications and contraindications for clinical zinc supplementation should be reconsidered.
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PMID:Divergent effects of zinc on different bacterial pathogenic agents. 784 97

A recombinant of toxic shock syndrome toxin 1 (TSST-1) which contains a single histidine-to-alanine mutation at residue 135 (H135A) was analyzed for toxicity and vaccine potential in a lipopolysaccharide (LPS)-potentiated mouse lethality model. The 50% lethal dose (LD50) of TSST-1 in BALB/c mice was 47.2 micrograms/kg, but H135A was not lethal when tested at a dose equivalent to 10 LD50s of TSST-1. Levels of tumor necrosis factor (TNF) and gamma interferon (IFN-gamma) in serum were, respectively, 10- and 50-fold higher in LPS-potentiated mice injected with 15 LD50s of TSST-1 than in mice given H135A. Mice injected with only TSST-1 did not have elevated levels of TNF or IFN-gamma in serum, while H135A plus LPS or LPS alone elicited identical, yet very low, levels of TNF and IFN-gamma. An enzyme-linked immunosorbent assay of H135A and TSST-1 with anti-TSST-1 serum yielded very similar dose-response curves, which strongly suggests that H135A serologically and conformationally resembles the native toxin. Mice immunized with H135A developed antibodies that recognized TSST-1 in an enzyme-linked immunosorbent assay and afforded protection against a 15-LD50 challenge of TSST-1 plus LPS. The pooled sera of mice immunized with either TSST-1 or H135A also prevented lymphocyte proliferation due to TSST-1.
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PMID:Biological activity of toxic shock syndrome toxin 1 and a site-directed mutant, H135A, in a lipopolysaccharide-potentiated mouse lethality model. 789 Mar 77

Mice (BALB/cJ, C3H/HeN, and C3H/HeJ) primed with actinomycin D became highly susceptible to lethal intoxication with staphylococcal enterotoxin B (SEB). The mice underwent toxicosis and toxic shock and died. Actinomycin D-primed C3H/HeN and C3H/HeJ mice showed equal sensitivity to SEB, suggesting that bacterial lipopolysaccharide derived from gram-negative bacteria in the gut may not be an important cofactor in intoxication. In a time course study of the illness, prominent pathological changes characterized by blood congestion and thickening of alveolar septa were seen in the lung, while blood congestion, inflammation, epithelial cell flattening, and villous blunting were seen in the small intestine. In lymphoid tissues, such as the spleen, congestion, inflammation, and lymphoid cell depletion were the major reactions. The pathological features of the mice had many similarities to those of rhesus monkeys intoxicated with intravenous SEB. The actinomycin D-primed C3H/HeJ mice are thus an ideal mouse model for studying SEB toxicosis and toxic shock.
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PMID:Increased susceptibility to staphylococcal enterotoxin B intoxication in mice primed with actinomycin D. 792 30

We examined the biological and kinetic characteristics of two new members of the intercrine family of cytokines. Human macrophage inflammatory peptides 2 alpha and beta (huMIP-2 alpha and beta) were compared to human interleukin 8 (huIL-8), neutrophil activating peptide 2 (huNAP-2), and N-formyl-L-methionyl-L-phenylalanine (fMLP). The huMIP-2 peptides were the least potent cytokine tested in triggering neutrophil degranulation. They were also less potent neutrophil chemotaxins than fMLP or huIL-8. However, they were more effective than NAP-2 in stimulating chemotaxis of neutrophils. The binding studies showed that huMIP-2 peptides could interact with specific receptors on human blood neutrophils. Moreover, huMIP-2 peptides competed for up to 60% of the huIL-8 binding sites on neutrophils whereas huIL-8 competed for almost 100% of either of the huMIP-2 peptide binding sites. These data suggest the huMIP-2 peptides have little or no affinity for 40% of the huIL-8 receptors. In addition, detectable amounts of mRNA for huMIP-2 alpha were found in samples from human alveolar macrophages stimulated with Staphylococcus aureus, toxic shock syndrome toxin-1 (TSST), but not in samples stimulated with S. aureus enterotoxin A (SEA) or Escherichia coli endotoxin (lipopolysaccharide = LPS). In conclusion, huMIP-2 alpha and beta are weak neutrophil stimulating agents, which may increase inflammation in diseases such as toxic shock syndrome.
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PMID:Biological and kinetic characterization of recombinant human macrophage inflammatory peptides 2 alpha and beta and comparison with the neutrophil activating peptide 2 and interleukin 8. 803 95

The role of tumor necrosis factor-alpha (TNF alpha) in the pathogenesis of severe bacterial infections has been studied extensively. However, the role of TNF beta, a lymphokine with biologic activities similar to those of TNF alpha, has received little attention. Therefore, the purpose of this study was to examine the production of TNF beta by peripheral blood mononuclear cells in response to lipopolysaccharide (LPS) and the superantigens staphylococcal toxic shock syndrome toxin 1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA). Though LPS was a more potent inducer of TNF alpha than was TSST-1 or SPEA, TSST-1 and SPEA were both more potent inducers of TNF beta. The superantigens TSST-1 and SPEA were more potent inducers of total TNF (TNF alpha and TNF beta) than was LPS. These data suggest that the induction of TNF beta synthesis may be a unique pathway by which superantigens associated with severe streptococcal and staphylococcal infections mediate shock and multiorgan failure characteristic of toxic shock syndrome.
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PMID:Superantigens associated with staphylococcal and streptococcal toxic shock syndrome are potent inducers of tumor necrosis factor-beta synthesis. 851 17


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