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 copper-zinc superoxide dismutase (CuZnSOD) gene resides on chromosome 21 and is overexpressed in Down syndrome (DS) patients. Transgenic CuZnSOD mice with elevated levels of CuZnSOD were used to determine whether, as in DS, overexpression of CuZnSOD was also associated with thymus and bone marrow abnormalities. Three independently derived transgenic CuZnSOD strains had abnormal thymi showing diminution of the cortex and loss of corticomedullary demarcation, resembling thymic defects in children with DS. Transgenic CuZnSOD mice were also more sensitive than control mice to in vivo injection of lipopolysaccharide (LPS), reflected by an earlier onset and enhanced apoptotic cell death in the thymus. This higher susceptibility to LPS-induced apoptosis was associated with an increased production of hydrogen peroxide and a higher degree of lipid peroxidation. When cultured under suboptimal concentrations of interleukin 3 or in the presence of tumour necrosis factor, bone marrow cells from transgenic CuZnSOD mice produced 2- to 3-fold less granulocyte and macrophage colonies than control. The results indicate that transgenic CuZnSOD mice have certain thymus and bone marrow abnormalities which are similar to those found in DS patients, and that the defects are presumably due to an increased oxidative damage resulting in enhanced cell death by apoptosis.
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PMID:Thymic abnormalities and enhanced apoptosis of thymocytes and bone marrow cells in transgenic mice overexpressing Cu/Zn-superoxide dismutase: implications for Down syndrome. 758 27

Survival after irradiation with LD100/30 (radiation dose lethal to 100% of mice in 30 days) is based on recovery of impaired hematopoietic function. Our previous studies using antibodies to interleukin-1 receptor (IL-1R), tumor necrosis factor (TNF), and IL-6 demonstrated that endogenous production of these three cytokines is required for untreated mice as well as mice protected with lipopolysaccharide (LPS), IL-1, or TNF to survive lethal irradiation. In this report we show that anti-c-kit ligand/steel factor (SIF) antibody similarly abrogates LPS- and IL-1-induced radioprotection. Furthermore, administration of this antibody to unmanipulated mice increased LD50/30 radiation lethality from 50% to 100%. Such an effect was not obtained using anti-IL-3, anti-IL-4, or anti-granulocyte-macrophage colony-stimulating factor antibody. Thus, like IL-1, TNF, and IL-6, SIF is required for survival from lethal irradiation.
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PMID:Inhibition of c-kit ligand/steel factor by antibodies reduces survival of lethally irradiated mice. 767 9

Interleukin-8 (IL-8) is a major neutrophil chemoattractant and functional stimulant that is induced by IL-1, tumor necrosis factor alpha (TNF alpha), and lipopolysaccharide (LPS). We report that recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 are also potent inducers of IL-8 messenger RNA (mRNA) accumulation and protein secretion by normal peripheral blood monocytes. Neutrophils produce IL-8 in response to GM-CSF but not to IL-3. In contrast, recombinant human granulocyte-CSF (rhG-CSF), at concentrations as high as 100 ng/mL, does not induce IL-8 in either cell type. rhGM-CSF also induces IL-8 mRNA expression and IL-8 protein in the promonocytic cell line, U-937, whereas rhG-CSF does not. IL-8 secretion by monocytes was stimulated within 2 hours after incubation with rhGM-CSF or rhIL-3. Stimulation of neutrophils with rhGM-CSF resulted in an increase in cell-associated IL-8 at 4 hours. At 24 hours, cell-associated IL-8 levels declined, whereas secreted IL-8 levels increased. In contrast, virtually all IL-8 induced in monocytes appeared as secreted protein. Neither rhGM-CSF nor rhIL-3 induced detectable secretion of IL-1, TNF alpha, or IL-6 protein by monocytes. rhGM-CSF, and to a lesser degree rhIL-3, potently stimulated IL-8 secretion in cultures of heparinized whole blood, whereas rhG-CSF had no significant effect on IL-8 secretion. Induction of IL-8 by GM-CSF may be physiologically important in enhancing the acute inflammatory response.
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PMID:Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. 767 12

1. Our previous work has shown that injection into mice of lipopolysaccharide (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) induces histidine decarboxylase (HDC), the enzyme forming histamine, in various tissues such as liver, lung, spleen and bone marrow, but not in the blood. The induction of HDC also occurs in nude mice and mast cell-deficient mice. On the other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the haematopoietic organs, i.e. bone marrow and spleen. In the present study, the effect of macrophage depletion on the induction of HDC was examined. 2. On day 1 after a single intravenous injection of a macrophage depletor (liposomes encapsulating dichloromethylene diphosphonate, which is toxic when ingested into macrophages), macrophages were almost completely depleted in the liver and reduced by about 50% in the spleen and bone marrow, but not significantly affected in the lung. On day 3, the degrees of the depletion were similar to those of day 1. In the spleen, macrophages were depleted in the red pulp, and there was a structural destruction. 3. In macrophage-depleted mice, the induction of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was potentiated in the lung and bone marrow. The induction of HDC was decreased only in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult rat, which is correspondingly inactive in haematopoiesis.5 These results indicate that the major cells in which HDC activity is induced in response to LPS, IL-1 and TNF are not circulating granulocytes, circulating monocytes, T cells derived from thymus, mast cells or phagocytic macrophages. Based on these results, we discuss the possibility that the major cells in which HDC was induced in non-haematopoietic and haematopoietic organs were endothelial cells and haematopoietic precursor cells respectively.
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PMID:Effects of macrophage depletion on the induction of histidine decarboxylase by lipopolysaccharide, interleukin 1 and tumour necrosis factor. 771 16

Bone marrow stromal cells produce cytokines that are essential for the proliferation and differentiation of hematopoietic stem and progenitor cells. Thus, regulation of cytokine production by bone marrow accessory cells is a critical aspect of stromal cell regulation of hematopoiesis. We have investigated the effect of two cytokines that have been demonstrated to modulate factor production by non-marrow accessory cells (i.e., transforming growth factor-beta 1 [TGF-beta 1] and interleukin-4 [IL-4]) on the induced expression of cytokine mRNA in a bone marrow-derived, cloned, murine stromal cell line +/+/-.LDA11. We showed that +/+/-.LDA11 cells can be induced with lipopolysaccharide (LPS), IL-1 alpha, or interferon-gamma (IFN-gamma) to express mRNA for monocyte chemoattractant protein-1 (MCP-1/JE), IFN-inducible protein-10 (IP-10), stem cell factor (SCF), and macrophage colony-stimulating factor (M-CSF) but not for IL-1 alpha, IL-3, or tumor necrosis factor-alpha (TNF-alpha). The expression of MCP-1/JE and IP-10 mRNA by these inducers was potentiated by TGF-beta 1 and IL-4. The augmentation by TGF-beta 1 of both mRNAs induced with IL-1 alpha was maximum when applied to the cells concurrently with the inducer; the IFN-gamma-induced expression of mRNAs was augmented even if the addition of TGF-beta 1 was delayed. Similarly, IL-4 potentiation of both mRNAs by either inducer progressively increased as the time between exposure to the inducer and exposure to IL-4 increased. Neither modulator altered the time course of mRNA expression by either inducer. TGF-beta 1- and IL-4-mediated augmentation of MCP-1/JE mRNA by IL-1 alpha or IFN-gamma was partially reversed by cycloheximide (CHX), whereas potentiation of IP-10 by either modulator remained unaffected. Increase in the stability of mRNA transcripts by TGF-beta 1 or IL-4 does not appear to play a role in the enhanced accumulation of mRNA in the presence of the modulators. These findings support a role for TGF-beta 1 and IL-4 as critical regulatory molecules in production of MCP-1 and IP-10 chemokines by stromal cells.
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PMID:Induction of chemokine mRNA in bone marrow stromal cells: modulation by TGF-beta 1 and IL-4. 776 3

When B cells from BALB/c mice were cultured with lipopolysaccharide (LPS) and interleukin-4 (IL-4), a large amount of IgE was detected in the culture supernatants. The IgE production from unseparated spleen cells cultured with LPS and IL-4 was less than the amount of IgE obtained from separated B cells. When syngeneic T cells were added to separated B cells cultures, which were subsequently stimulated with LPS and IL-4, less IgE was produced, as compared to cultures without T cells. The hypothesis that T cells, or factors secreted by these cells, inhibit IgE production is supported by the fact that the degree of suppression of IgE production paralleled the number of T cells added. CD8(+)-enriched T cells were slightly more suppressive than CD4(+)-enriched T cells. Addition of exogenous IL-3 was only partially suppressive. These observations suggest that IL-4 added to unseparated spleen cells in vitro stimulates B cells for IgE production and also stimulates T cells. Lymphokines secreted by these stimulated T cells may in turn act on B cells. Some of these lymphokines, such as interferon-gamma and IL-2, may have a suppressive action on IgE production.
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PMID:Suppression of IgE production in unseparated spleen cell cultures. 790 2

This study was designed to examine the possible mechanisms by which macrolide antibiotics favorably influence the clinical course of asthmatic patients. In the first set of experiments, we investigated the effect of roxithromycin (RXM), a newly synthesized macrolide antibiotic, on in vitro cytokine secretion by mitogen-activated human peripheral blood leukocytes. RXM suppressed the secretion of T cell cytokine interleukins (IL) 2-4 and monocyte cytokine tumor necrosis factor alpha. This inhibitory effects on cytokine secretion was dose dependent and firstly noted at a concentration of as little as 0.5 microgram/ml which is much lower than therapeutic blood levels. In the second part of experiments, we examined the influence of RXM on cytokine appearance in mouse lung extract induced by lipopolysaccharide (LPS) inhalation and on bronchial responsiveness to methacholine in LPS-treated mice. As compared with mice pretreated with phosphate-buffered saline, RXM administered orally at a single dose of 5 mg/kg once a day for 21 days inhibited the appearance of IL-3, IL-4, IL-5, and tumor necrosis factor alpha in aqueous lung extracts. Pretreatment with RXM also decreased the bronchial responsiveness to methacholine induced by intratracheal injection of LPS. We conclude that the attenuating effect of macrolide antibiotics on asthmatic syndromes might be explained partially by their inhibitory effects on cytokine secretion from leukocytes.
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PMID:Antiasthmatic activity of a macrolide antibiotic, roxithromycin: analysis of possible mechanisms in vitro and in vivo. 792 33

Partial resorption or abortion (depending upon the stage of gestation) can be induced with lower doses of lipopolysaccharide (LPS) (DIFCO) and human R-TNF than previously demonstrated. As can be expected, the abortion-prone CBA x DBA/2 and B10 x B10.A mating combinations are the most sensitive to such low doses. LPS synergizes with low doses of IL-2, gamma interferon, poly(I).poly(C) 12U. Treatment by GM-CSF, IL-3, or anti-natural killer antiserum decreases both TNF levels and abortion rates. Similar prevention of induced resorptions are obtained with either a neutralizing polyclonal rabbit anti-TNF antiserum or with pentoxyfilline, which has been shown to reduce resorption rates in CBA x DBA/2 pregnancies. More important, abortions induced by low doses of LPS or R-TNF can be prevented by alloimmunization. During late gestation, on the contrary, LPS- or TNF-induced delivery cannot be counteracted by alloimmunization nor by a progesterone-induced blocking factor, at least in the regimens employed by us. Therefore, although resorptions and parturition share common pathways consisting of immune mediators, they are not regulated similarly by the maternal immune system.
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PMID:Synergy of lipopolysaccharide and inflammatory cytokines in murine pregnancy: alloimmunization prevents abortion but does not affect the induction of preterm delivery. 806 21

Interleukin-3 (IL-3, multi-CSF) is a growth factor for a variety of hematopoietic progenitor cells. Recently, microglial cells, the resident macrophages of the central nervous system (CNS) have been shown to proliferate in the presence of IL-3 both in vivo and in culture. Data obtained from cultured astrocytes gave rise to the hypothesis that astrocytes synthesize the microglial growth factor. This is the first report identifying rat microglial cells themselves as a source of IL-3. Culture media conditioned by isolated microglia enhanced microglial proliferation above fresh media controls. IL-3 polypeptide was detected in both conditioned media (CM) and in microglial cells by Western blotting and immunoprecipitation. Furthermore, anti-IL-3 antibodies were able to inhibit microglial proliferation induced by conditioned media. mRNAIL-3 was present in single microglial cells as revealed by in situ hybridization. Total RNA prepared from purified microglia yielded a single PCR amplification product. Identity of the PCR product was confirmed by Southern blot hybridization using a cDNAIL-3 probe and by DNA sequencing. Expression of mRNAIL-3 was observed in both absence and presence of lipopolysaccharide, a bacterial endotoxin, that commonly induces expression of inflammatory cytokines and inhibits microglial proliferation. It is concluded that IL-3 expression in ensuring the recruitment of enhanced numbers of immunocompetent cells at sites of lesion. In the light of weak immune reactions in the brain, it is hypothesized that the expression of a characteristic T cell feature in monocyte-derived microglia may be a partial compensation of T cell functions in brain lesions.
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PMID:Rat microglial interleukin-3. 812 Jan 42

Interleukin 1 receptor antagonist (IL-1ra) is induced in monocytes stimulated with lipopolysaccharide (LPS) or cultured on adherent immunoglobulin G (IgG). We examined the effects of various cytokines on monocyte IL-1ra protein production and compared it to IL-1 beta, which is regulated differently. IL-3 and GM-CSF induced near equivalent amounts of IL-1ra protein as does LPS. IL-1 alpha and IL-4 were weaker inducers. IL-3 and GM-CSF did not affect LPS or IgG induction of IL-1ra or LPS-induced IL-1 beta. However, our data confirmed that IL-4 up-regulated LPS-induced IL-1ra and down-regulated LPS-induced IL-1 beta. The kinetics of IL-1ra production by monocytes varied between stimulation with adherent IgG and cytokines or LPS. Cells cultured on adherent IgG exhibited a higher level of and more prolonged IL-1ra production. Relative IL-1ra mRNA levels after 8 h were in the order: adherent IgG > LPS or GM-CSF > IL-1 alpha, IL-3 or IL-4. The following cytokines failed to induce IL-1ra production: IL-2, IL-6, G-CSF, M-CSF, IFN-gamma, TGF beta 1, TGF beta 2, TNF alpha, acidic and basic FGF, PDGF and EGF. These results suggest that IL-1 alpha, IL-3, IL-4 and GM-CSF may play important roles in regulating monocyte IL-1ra production and that different mechanisms may be involved in induction of IL-1ra by adherent IgG in comparison to LPS or other cytokines.
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PMID:Interleukin 1 receptor antagonist production in human monocytes is induced by IL-1 alpha, IL-3, IL-4 and GM-CSF. 814 95


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