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 recently shown that interleukin-1 is a potent stimulus of gene expression and production of leukocyte chemotactic factors, colony-stimulating factors, and interleukin-6 in human mesangial cells in culture. Here, we sought to determine whether interleukin-1 induces its own gene expression in human mesangial cells. Interleukin-1 mRNA levels were quantitated by Northern blot analysis with total cellular RNAs isolated from human mesangial cells exposed for 6 h to medium alone or in the presence of human recombinant interleukin-1 beta (1 to 100 ng/mL). Interleukin-1 induced interleukin-1 mRNA expression in a dose-dependent manner. An additional finding of this study was that human mesangial cells constitutively express the 80 kd interleukin-1 receptor type 1 gene. When human mesangial cells were exposed to interleukin-1, interleukin-1 receptor expression was not modified. Similarly, other stimuli like tumor necrosis factor, transforming growth factor beta, or interleukin-6 did not modulate interleukin-1 receptor expression. Recombinant interleukin-1 receptor antagonist blocked the interleukin-1 mRNA as well as interleukin-6 and interleukin-8 mRNA accumulation induced by interleukin-1 beta. Lipopolysaccharide, which is a known stimulus for interleukin-1 transcription in several cell types, also induced interleukin-1 mRNA accumulation, thus indicating that lipopolysaccharide mediates interleukin-1 gene activation in human mesangial cells through an interleukin-1-independent pathway. These data support the pivotal role of interleukin-1 in regulating mesangial cell cytokine genes and may be taken to indicate the existence of an interleukin-1-mediated positive feedback loop that might control the secretion of active cytokines within the glomeruli when an immunological or inflammatory injury takes place.
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PMID:Interleukin-1 regulates cytokine gene expression in human mesangial cells through the interleukin-1 receptor type 1. 138 59

To investigate the role of interleukin-1 (IL-1) in lipopolysaccharide (LPS)-induced sickness behavior, rats were injected with recombinant human interleukin-1 receptor antagonist (IL-1ra), an endogenous cytokine able to block most of the biological effects of IL-1 both in vivo and in vitro. Intraperitoneal injection of IL-1ra (3 mg/rat) attenuated the depressive effect of LPS (250 micrograms/kg) on social exploration and body weight when both treatments were injected peripherally. Intracerebroventricular injection of IL-1ra (60 micrograms/rat) did not block the effects of peripherally injected LPS. These data indicate that the peripherally mediated effects of IL-1 account for a significant part of LPS-induced sickness behavior.
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PMID:Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat. 138 28

A human recombinant interleukin-1 receptor antagonist (IL-1ra) recognizes the two known IL-1 receptors and blocks the binding and many biological effects of both IL-1 alpha and IL-1 beta. The effectiveness of IL-1ra in modifying the fever and plasma IL-6 responses elicited by lipopolysaccharide (LPS) in vivo was tested in Fischer 344 rats. Animals that received IL-1ra 0.5 mg/kg intraperitoneally followed 10 min later by 10 micrograms/kg of LPS displayed significantly lower mean fever responses 2-4 h after injection than rats that received vehicle and LPS (0.48 +/- 0.13 vs. 0.95 +/- 0.16 degrees C, P = 0.016). Plasma levels of IL-6 at 4 h after injection were not different in IL-1ra-treated rats compared with controls (407,725 vs. 729,169 U/ml). Based on our previous finding that preadministration of antiserum to IL-1 beta markedly suppressed plasma IL-6 after LPS, and recent evidence that molar excesses of IL-1ra blocked IL-1-induced circulating IL-6 levels, the possibility that IL-1 is responsible for the induction of bioactive IL-6 during inflammation cannot be ruled out. Similarly, the inability of the IL-1ra to completely suppress the febrile responses of rats to LPS in the present study may be dose related. Alternatively, the induction of bioactive IL-6 by IL-1 in the rat may be mediated primarily through some receptor other than the type I (e.g., the type II receptor).
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PMID:Human IL-1 receptor antagonist partially suppresses LPS fever but not plasma levels of IL-6 in Fischer rats. 141 54

mRNA expression and protein production of interleukin-1 alpha, interleukin-1 beta and intracellular and secreted forms of an interleukin-1 receptor antagonist were measured in visually confluent monolayers of unstimulated cultured human retinal pigment epithelial cells and after cells were stimulated with recombinant cytokines. Using reverse transcription polymerase chain reaction, transcripts for interleukin-1 alpha and interleukin-1 beta were not detected in unstimulated cells from any of six donors whereas mRNA expression for both interleukin-1 alpha and interleukin-1 beta was readily induced in all six cell lines after cells were stimulated with recombinant IL-1 (alpha or beta), tumor necrosis factor alpha, or lipopolysaccharide. The combination of cycloheximide and recombinant interleukin-1 caused a 14-fold enhancement of interleukin-1 alpha and interleukin-1 beta mRNA expression above that observed after cells were stimulated with interleukin-1 alone. After stimulation by interleukin-1, cells produced intracellular interleukin-1 alpha protein, but did not secrete it into medium. In contrast, interleukin-1 beta protein was not detected in cell lysates or conditioned-medium after stimulation with interleukin-1. An intracellular interleukin-1 receptor antagonist was expressed constitutively by human retinal pigment epithelial cells; mRNA transcripts were enhanced in a dose and time dependent manner after cells were exposed to recombinant interleukin-1 or tumor necrosis factor alpha. In contrast, mRNA for a secreted form of the interleukin-1 receptor antagonist was not detected under basal conditions or after cells were stimulated by recombinant cytokines. Interleukin-1 receptor antagonist protein was found primarily in cell lysates; little interleukin-1 receptor antagonist protein was secreted by the cells. The presence of cell-associated interleukin-1 receptor antagonist was confirmed by immunocytochemistry. Levels of cell-associated IL-1 receptor antagonist protein were not significantly influenced by recombinant interleukin-1 or tumor necrosis factor alpha. Endogenous expression of interleukin-1 receptor antagonist may attenuate the effect of exogenous or endogenous interleukin-1, thus providing the RPE cell a means of maintaining interleukin-1 homeostasis in ocular inflammatory disease.
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PMID:Expression of interleukin-1 alpha, interleukin-1 beta, and an interleukin-1 receptor antagonist in human retinal pigment epithelial cells. 142 65

These studies compared the release of interleukin-1 receptor antagonist (IL-1 RA) from alveolar macrophages and peripheral blood monocytes. The cells were cultured in medium containing various amounts of heat-inactivated fetal calf serum (FCS), granulocyte-macrophage colony-stimulating factor (GM-CSF), lipopolysaccharide (LPS), and immunoglobulin G (IgG). In serum-free medium alone, IL-1 RA release was similar from macrophages and monocytes. Increasing FCS concentration caused a significant upregulation of IL-1 RA release in macrophages but not in monocytes. GM-CSF caused a small increase in both cell types. LPS caused downregulation of IL-1 RA release from monocytes but not from macrophages. IgG did not affect IL-1 RA release in either cell group. These studies demonstrate that regulation of IL-1 RA release is different in monocytes and macrophages.
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PMID:IL-1 receptor antagonist release is regulated differently in human alveolar macrophages than in monocytes. 144 22

In this report, administration of a recombinant interleukin-1 receptor antagonist protein to mice was found to inhibit induction of colony-stimulating factor as well as induction of early endotoxin tolerance by lipopolysaccharide. These findings provide direct evidence that interleukin-1 is an intermediate in these two lipopolysaccharide-induced phenomena.
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PMID:An interleukin-1 receptor antagonist blocks lipopolysaccharide-induced colony-stimulating factor production and early endotoxin tolerance. 182 85

In this study, hypoglycemia induced by injection of lipopolysaccharide (LPS) or the recombinant cytokine interleukin-1 alpha or tumor necrosis factor alpha (administered alone or in combination) was compared. LPS-induced hypoglycemia was reversed significantly by recombinant interleukin-1 receptor antagonist.
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PMID:Roles of interleukin-1 and tumor necrosis factor in lipopolysaccharide-induced hypoglycemia. 182 92

Colony-stimulating factor 1 (CSF-1) can act on mature macrophages to modulate their production of inflammatory cytokines. A cDNA encoding the interleukin-1 receptor antagonist (IL-1Ra) was cloned by subtractive hybridization from a CSF-1-stimulated murine macrophage cell line, sequenced, and expressed in mammalian and bacterial cells. Mouse IL-1Ra is a 22-Kd glycoprotein that is 76% identical to its human counterpart, shows considerably less similarity to IL-1 alpha and IL-1 beta, and competes with IL-1 alpha for binding to the type I IL-1 receptor normally expressed on T cells and fibroblasts. CSF-1 treatment of mouse bone marrow-derived macrophages led to a rapid and sustained increase in IL-1Ra mRNA during the G1 phase of the cell cycle as well as to increases in mRNAs encoding IL-1 alpha and IL-1 beta. Cycloheximide inhibited CSF-1-induced IL-1 alpha mRNA synthesis, but augmented IL-1 beta mRNA production and did not affect induction of IL-1Ra mRNA. No IL-1Ra mRNA was observed in CSF-1-stimulated mouse fibroblasts engineered to express CSF-1 receptors, demonstrating that its regulation depends on cell context and can be dissociated from the proliferative response. In agreement, bacterial lipopolysaccharide, a nonmitogenic activator, also induced IL-1Ra and IL-1 mRNAs in macrophages. Unlike IL-1 alpha and beta, IL-1Ra contains a signal peptide. The kinetics of its induction and its ability to gain access to the secretory compartment imply that IL-1Ra may be secreted more efficiently than IL-1, and suggest that macrophages both positively and negatively regulate the IL-1 response.
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PMID:Cloning and expression of murine interleukin-1 receptor antagonist in macrophages stimulated by colony-stimulating factor 1. 183 Apr 98

We explored the ex vivo alteration in the cytokine release of stimulated blood taken from healthy volunteers treated subcutaneously with 480 micrograms granulocyte colony-stimulating factor (G-CSF). In a double-blind, controlled, randomized study with 21 volunteers who received G-CSF once or twice 24 hours apart, we measured lipopolysaccharide (LPS)-inducible release of various cytokines and soluble receptors at different times after treatment. At day 1 after a single dose of G-CSF, mediator release was also initiated with muramyl dipeptide, Staphylococcus aureus enterotoxin A, lipoteichoic acid, streptolysin O, complement factor C5a, phytohemagglutinin, or phorbol myristate acetate. In blood from G-CSF-treated subjects, our major findings were (1) a maximal 12-fold increase in interleukin-1 receptor antagonist (IL-1ra) release and an increase of both the p55 and p75 soluble tumor necrosis factor (TNF) receptors; (2) a reduction in TNF release when using all the various stimuli described except LPS; (3) an increase in G-CSF and, to lesser extent, in IL-6, IL-8, and IL-10 release; and (4) an attenuation of interferon-gamma (IFN-gamma) and granulocyte-macrophage (GM)-CSF release. Our findings demonstrate that the major effect of G-CSF treatment is a change in the responsiveness of blood towards a variety of stimuli, which we interpret as a shift toward an antiinflammatory cytokine response.
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PMID:Effect of granulocyte colony-stimulating factor treatment on ex vivo blood cytokine response in human volunteers. 753 16

Bovine kappa-caseinoglycopeptide (residues 106-169, CGP) bound to mouse plastic-adherent cells. A culture supernatant prepared from mouse spleen cells and plastic-adherent cells cultured with CGP significantly inhibited the lipopolysaccharide-induced proliferative response of mouse spleen lymphocytes. The inhibition of proliferation by the culture supernatant was completely overcome by the addition of the anti-interleukin-1 receptor antagonist antibody.
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PMID:Induction of an interleukin-1 receptor antagonist-like component produced from mouse spleen cells by bovine kappa-caseinoglycopeptide. 761 8


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