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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bioassay and northern blot analyses revealed that, among several functional murine macrophage (M phi) clones, lipopolysaccharide (LPS) stimulation generated in distinct induction levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF). When compared with these induction profiles, the M phi clones could be classified into two types; G type (G-CSF GM-CSF-M-CSF+) and GM type (G-CSF +/- GM-CSF M-CSF+) of M phi clones. Unlike G-CSF and GM-CSF that were inducible factors, M-CSF mRNA was constitutively expressed without stimulation and was differentially controlled between the G and GM types; LPS induction decreased M-CSF mRNA in the former, but increased it in the latter. Further northern blot analysis revealed that interferon-gamma (IFN-gamma) suppressed constitutive expression of M-CSF mRNA, and that costimulation with both LPS and IFN-gamma reduced expression of G-CSF and M-CSF mRNA in the G type of M phi clone, but induced higher expression of GM-CSF and M-CSF mRNAs in the GM type of M phi clone compared with LPS alone. However, in either case, IFN-gamma completely inhibited LPS-induced production of active CSF of the M phi clones, which was observed even in IFN-gamma pretreatment, and also abrogated autoactivation of GM-CSF. Our present results suggested that murine M phi clones had differentially regulated expression of CSFs and that IFN-gamma had a regulatory function of inhibiting CSF production of murine M phi s.
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PMID:Differential expression of colony-stimulating factor (CSF) in murine macrophage clones: interferon-gamma-mediated inhibition of CSF production. 752 Aug 41

Homeobox genes encode transcription factors known to be important morphogenic regulators during embryogenesis. An increasing body of work implies a role for homeobox genes in both hematopoiesis and oncogenesis. We have analyzed the role of the homeobox gene, HOX B7, in the program of differentiation of the biphenotypic myeloid cell line, HL60. Induction of monocytic differentiation in HL-60 cells by vitamin D3 resulted in rapid expression of HOX B7 mRNA, but stimulation with phorbol ester or dimethyl sulfoxide (DMSO) did not. Constitutive overexpression of HOX B7 in the HL60 cell line inhibited the granulocytic differentiation associated with stimulation with DMSO or retinoic acid, but had no effect on the monocytic differentiation induced by vitamin D3. Normal human monocytes do not constitutively express HOX B7, nor are they able to be induced to do so by stimulation with colony-stimulating factor 1 (CSF-1) and gamma interferon (IFN gamma), or with vitamin D3 and lipopolysaccharide. Human bone marrow (BM) cells were found to express HOX B7 in response to granulocyte-macrophage CSF (GM-CSF) and antisense oligonucleotides directed against HOX B7 inhibited the formation of colonies derived from GM-CSF-stimulated BM. These data suggest a critical role for HOX B7 in myelomonocytic differentiation.
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PMID:The role of the homeobox gene, HOX B7, in human myelomonocytic differentiation. 753 May 3

Small numbers of CD34+ primitive hematopoietic progenitors are found in normal human peripheral blood. These cells differentiate to myeloid or lymphoid lineage under the influence of different growth factors. We investigated the effects of IL5 and other growth factors on the production of eosinophils from peripheral blood CD34+ cells. CD34+ cells were enriched from normal donors by apheresis and positive selection using an affinity column and plated in agarose with different combinations of cytokines. At 14 days of growth a triple stain technique was used to identify eosinophil, monocyte, and neutrophil colonies. IL5 alone did not support colony growth from CD34+ cells. In contrast, GM-CSF and IL3 alone or together without added IL5 supported the generation of more than 50% pure eosinophil colonies. Addition of IL5 did not change the total number of colonies, but increased the fraction of pure eosinophil colonies to over 70%. Addition of G-CSF reduced the percentage of eosinophil colonies and increased the percentage of neutrophil colonies. Under the best conditions for eosinophil colony growth (IL3+GM-CSF+IL5), the addition of interferon-alpha or bacterial lipopolysaccharide inhibited colony growth by 51 and 58%, respectively. Addition of interferon-gamma, tumor necrosis factor-alpha, or dexamethasone had no effect on eosinophil colonies. Since IL5 alone did not support colony growth from CD34+ cells, we determined when IL5-responsive cells appeared in culture. Cells were grown initially with IL3 + GM-CSF in suspension, washed, and plated in agarose with IL5 alone. Only when progenitors were grown at least 3 days could IL5 serve as the single growth factor supporting pure eosinophil colony growth (47 colonies/10(4) cells plated at Day 3 and 134 colonies/10(4) cells at Day 7). We used neutralizing anti-IL5 antibodies to demonstrate that this late acting IL5 growth effect was specific, and that differentiation of eosinophils in the presence of IL3 + GM-CSF was IL5 independent. Using reverse-transcriptase polymerase chain reaction, the mRNA encoding the eosinophil-specific protein eosinophil peroxidase (EPO) was not detected in Day 0 CD34+ cells, but was demonstrated by Day 3 of culture. We conclude that within 3 days of culture, peripheral blood CD34+ cells can become committed to the eosinophil lineage as demonstrated by responsiveness to IL5 and production of EPO transcripts.
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PMID:Modulation of growth and differentiation of eosinophils from human peripheral blood CD34+ cells by IL5 and other growth factors. 753 Nov 18

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

An injection of Escherichia coli lipopolysaccharide (LPS) increased the activity of histidine decarboxylase (HDC) in bone marrow (BM) cells of C3H/HeN mice much more than in C3H/HeJ mice, which are resistant to various effects of LPS. In WBB6/F1 (W/Wv) mice, which are genetically deficient in mast cells, HDC activity increased more than in C3H/HeN mice. Cultured BM cells of W/Wv mice spontaneously synthesized histamine in a HDC-dependent way. LPS caused a slight increase in HDC-associated histamine synthesis by these cells. Treatment of the BM cells with murine recombinant granulocyte-macrophage colony stimulating factor (mrGM-CSF) increased the histamine synthesis. In addition, treatment with mrGM-CSF made the cells respond to LPS by a dose-dependent increase in HDC activity and histamine synthesis. Most dish-adherent BM cells that had been treated with both mrGM-CSF and LPS for 48 h were stained for nonspecific esterase and not for chloroacetate esterase, and had twice as much HDC activity as the nonadherent cells had. Immunocytochemical analysis of the BM cells of W/Wv mice treated with both mrGM-CSF and LPS showed that HDC was in the cytoplasm of cells having Mac-1, a macrophage-differentiation antigen. These results suggest that cells of the macrophage lineage in the BM of mice synthesize histamine.
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PMID:Histamine synthesis by cells of the macrophage lineage in bone marrow of mice. 754 1

The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability. 757 80

Prolonged culture of human peripheral blood monocytes hPBMs requires the addition of both granulocyte/macrophage-colony-stimulating factor (GM-CSF) and interferon (IFN)-gamma. Cultured hPMBs challenged with lipopolysaccharide produced large amounts of several cytokines but very little interleukin (IL)-10. However, when GM-CSF and IFN-gamma were omitted from the cultures, IL-10 production was readily demonstrated. Addition of IL-10 to the cultures potently inhibited the production of several cytokines and, in the presence of GM-CSF and IFN-gamma, there was no loss in cell number. In contrast, when IL-10 was added to cultures in the absence of GM-CSF and IFN-gamma, there was an accelerated loss of viable cells. A monoclonal antibody to IL-10, which had no effect on cell survival in the presence of GM-CSF and IFN-gamma, partly prevented the loss of cells which occurred in the absence of IL-10 and these additives. Preliminary studies suggest that inclusion of anti-IL-10 can partly prevent the apoptosis which occurs when GM-CSF and IFN-gamma are omitted from the cultures. These observations suggest that there is a cause and effect relationship between the failure of hPBMs to produce IL-10 when they are cultured in the presence of GM-CSF and IFN-gamma and protection from apoptosis by these additives.
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PMID:Evidence that granulocyte/macrophage-colony-stimulating factor and interferon-gamma maintain the viability of human peripheral blood monocytes in part by their suppression of IL-10 production. 761 23

We have previously demonstrated that human peripheral blood low density mononuclear cells cultured in granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 develop into dendritic cells (DCs) that are extremely efficient in presenting soluble antigens to T cells. To identify the mechanisms responsible for efficient antigen capture, we studied the endocytic capacity of DCs using fluorescein isothiocyanate-dextran, horseradish peroxidase, and lucifer yellow. We found that DCs use two distinct mechanisms for antigen capture. The first is a high level of fluid phase uptake via macropinocytosis. In contrast to what has been found with other cell types, macropinocytosis in DCs is constitutive and allows continuous internalization of large volumes of fluid. The second mechanism of capture is mediated via the mannose receptor (MR), which is expressed at high levels on DCs. At low ligand concentrations, the MR can deliver a large number of ligands to the cell in successive rounds. Thus, while macropinocytosis endows DCs with a high capacity, nonsaturable mechanism for capture of any soluble antigen, the MR gives an extra capacity for antigen capture with some degree of selectivity for non-self molecules. In addition to their high endocytic capacity, DCs from GM-CSF + IL-4-dependent cultures are characterized by the presence of a large intracellular compartment that contains high levels of class II molecules, cathepsin D, and lysosomal-associated membrane protein-1, and is rapidly accessible to endocytic markers. We investigated whether the capacity of DCs to capture and process antigen could be modulated by exogenous stimuli. We found that DCs respond to tumor necrosis factor alpha, CD40 ligand, IL-1, and lipopolysaccharide with a coordinate series of changes that include downregulation of macropinocytosis and Fc receptors, disappearance of the class II compartment, and upregulation of adhesion and costimulatory molecules. These changes occur within 1-2 d and are irreversible, since neither pinocytosis nor the class II compartment are recovered when the maturation-inducing stimulus is removed. The specificity of the MR and the capacity to respond to inflammatory stimuli maximize the capacity of DCs to present infectious non-self antigens to T cells.
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PMID:Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. 762 94

The high-affinity receptors for interleukin-3 (IL-3), GM-CSF, and IL-5 are composed of a ligand binding (alpha-) and a transducing (beta-) subunit. Two distinct transducing subunits (clones AIC2A and AIC2B) have been cloned from mouse, whereas in humans, only one (common) beta-subunit (beta c) has been found. A PCR-based cloning strategy was used to obtain a full-length cDNA sequence from rat microglia including 5'-untranslated regions. Sequence analysis revealed a number of features indicative of the presence of only one beta-subunit in the rat. Most likely, the new rIL-3R beta cDNA is the rat equivalent of human respective murine (AIC2B) beta c subunits. Regulation of rIL-3R beta mRNA expression was investigated in cultured microglia and in vivo. Purified microglia expressed significant amounts of rIL-3R beta mRNA. Addition of lipopolysaccharide (LPS) resulted in a marked upregulation of rIL-3R beta mRNA within approximately 4 hr. No downregulation was observed within 1 week's treatment. No rIL-3R beta mRNA was detectable in normal rat brain. However, 3 hr after a single injection of LPS into the tail vein of a rat, a marked induction of receptor mRNA occurred in a variety of brain regions. Transcriptional rates subsided significantly after 24 hr. rIL-3R beta mRNA was visualized by in situ hybridizations with cRNA antisense probes in ramified cells formerly characterized as microglial cells. rIL-3R beta mRNA was also induced in rat brain after occlusion of middle cerebral artery (MCAO).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cloning of rat interleukin-3 receptor beta-subunit from cultured microglia and its mRNA expression in vivo. 764 20

Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-alpha (IFN), tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1 alpha, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1 alpha. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1 alpha and IL-1 beta remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.
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PMID:Cytokine induction by the immunomodulators imiquimod and S-27609. 766 93


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