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)

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

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

To investigate the functional change of stromal cells along with differentiation, we used a differentiation-inducible mouse embryo fibroblast cell line, C3H10T1/2 (10T1/2). Stably determined preadipocyte and myoblast cell lines were established after a brief exposure of 10T1/2 cells to 5-azacytidine. These cell lines terminally differentiated into adipocytes and myotubes, respectively, under appropriate conditions. The hematopoiesis-supporting ability of each 10T1/2-derived cell line was examined by coculture with FACS-sorted murine hematopoietic stem cells (Thy-1lo c-kit+ Lin-). The number of granulocyte-macrophage progenitors (CFU-GM) was slightly reduced after 7 days of culture with parent 10T1/2 fibroblasts, whereas a marked increase in CFU-GM number was observed when the cells were cultured on preadipocytes. Mature adipocytes and myogenically determined cell lines, on the other hand, did not support CFU-GM growth. Further, Northern analysis showed that the preadipocyte cell line acquired the ability to produce a significant amount of stem cell factor (SCF), interleukin-6 (IL-6), leukemia inhibitory factor, and macrophage colony-stimulating factor mRNAs in response to IL-1 or lipopolysaccharide stimulation. Terminal adipocytic differentiation resulted in reduced ability to express these cytokine mRNAs. Similarly, highest IL-6 activity was detected in the supernatant of preadipocyte culture, whereas adipocytes did not secrete IL-6 even after IL-1 stimulation. Interestingly, hematopoiesis-nonsupporting myoblasts and myotubes also expressed abundant SCF mRNA, suggesting that SCF, per se, may not be sufficient for stem cell growth and survival. The 10T1/2-derived cell lines could provide a valuable tool to aid in the analysis of stromal cell development and the search for novel stromal factors.
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PMID:Changes in hematopoiesis-supporting ability of C3H10T1/2 mouse embryo fibroblasts during differentiation. 768 Feb 42

Some studies have suggested that the addition of ciprofloxacin to in vitro cultures of mitogen-stimulated lymphocytes exerts inhibitory effects on cell cycle progression and immunoglobulin (Ig) secretion. We tested the effects of this drug on some immunity parameters in BALB/c mice. Mice treated intraperitoneally with ciprofloxacin (10 mg/kg of body weight per day) for 3 consecutive days and immunized with sheep erythrocytes 24 h after the last injection showed significant suppression of hemolytic IgG-forming cells, whereas the response of IgM-forming cells remained unchanged. When treatment lasted 7 days the response of antibody-forming cells was not modified. When the 3-day treatment was started at 24 h after immunization with sheep erythrocytes, the response of IgM-forming cells was increased, whereas the response of IgG-forming cells was suppressed. Delayed-type hypersensitivity to sheep erythrocytes was significantly suppressed in animals that received the 3-day treatment with ciprofloxacin and were immunized subcutaneously 24 h after the last injection. In vitro proliferation of lymphocytes from ciprofloxacin-treated mice in response to either lipopolysaccharide or concanavalin A was also suppressed. Leukopenia and an increase in the level of granulocyte-macrophage colony-forming cells in bone marrow were also observed in ciprofloxacin-treated mice. These results, together with those from other reports, suggest that modification of the biological responses by ciprofloxacin is a complex phenomenon that may be influenced by several factors.
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PMID:Modification of immune response in mice by ciprofloxacin. 769 98

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

Cells of monocytic lineage (Mo) persistently infected with human immunodeficiency virus (HIV) have been suspected to be a major reservoir for in vivo transmission of virus to susceptible target cells. Cellular events and mechanisms that upregulate viral gene expression in such cells are important issues. Because the traffic of such cells is central to biodistribution of HIV, we have explored the impact of interaction of endothelium with HIV-1-infected U1 promonocytic cells. Coculturing of U1 with human umbilical endothelial cells (HUVEC) for 24 to 72 hours in the absence of stimulation induced HIV-1 p24 biosynthesis significantly. Antibody-blocking experiments indicated that CD11/CD18 integrins play a role in upregulation of HIV expression elicited by interaction with HUVEC. Engagement of CD11b/CD18 by adherence of U1 to surfaces coated with either the cognate ligand fibrinogen or monoclonal antibody specific for CD11b/CD18 also enhanced p24 biosynthesis. Furthermore, endothelial cells were found to constitutively synthesize and secrete soluble factors that enhanced HIV-1 synthesis. The enhancing factors, of estimated size 10 to 45 kD, were induced in HUVEC to high levels by monokines or by lipopolysaccharide, resulting in markedly enhanced HIV-1 expression by U1. These endothelial cell-derived HIV-1-enhancing factors consist of, among others, interleukin-6 (IL-6), IL-1 beta, and granulocyte-macrophage CSF (GM-CSF). Our results suggest that activation of HIV biosynthesis in infected Mo via interaction with endothelium may impact significantly on the tissue distribution and pathogenesis of HIV infections.
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PMID:Upregulation of human immunodeficiency virus-1 in chronically infected monocytic cell line by both contact with endothelial cells and cytokines. 791 48

Macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-macrophage CSF (GM-CSF) have been shown to increase human monocyte urokinase-type plasminogen-activator (u-PA) activity with possible consequences for cell migration and tissue remodeling; because monocyte u-PA activity is likely to be controlled in part also by the PA inhibitors (PAIs) made by the cell, the effect of M-CSF and GM-CSF on human monocyte PAI-2 and PAI-1 synthesis was investigated. To this end, elutriation-purified human monocytes were treated in vitro with purified recombinant human M-CSF and GM-CSF, and PAI-2 and PAI-1 antigen and mRNA levels measured by specific enzyme-linked immunosorbent assays and Northern blot, respectively. Each CSF could enhance the protein and mRNA levels of PAI-2 and PAI-1 at similar concentrations for each product. This similar regulation of monocyte PAI expression in response to the CSFs contrasted with that found for the effects of lipopolysaccharide, transforming growth factor-beta and a glucocorticoid. Therefore, PAIs may be modulating the effects of the CSFs on monocyte u-PA activity at sites of inflammation and tissue remodeling.
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PMID:Macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor stimulate the synthesis of plasminogen-activator inhibitors by human monocytes. 826 Jul

Previously we described that bacterial lipopolysaccharide (LPS) promoted DNA synthesis and supported the cell viability in the factor-dependent macrophage cell lines BDM-1 and BDM-1W3 in the absence of colony-stimulating factor (CSF). To further examine this phenomenon, in the present study we examined the effects of serum on CSF-dependent proliferation and LPS-induced DNA synthesis in BDM-1 and BDM-1W3 cells. Fetal calf serum (FCS) was required for CSF-dependent proliferation in BDM-1 and BDM-1W3 cells. FCS was also required for LPS-induced DNA synthesis in BDM-1W3 cells. However, at concentrations higher than 0.2%, FCS inhibited LPS-induced DNA synthesis in BDM-1W3 cells in a dose-dependent manner. To obtain the inhibitory activity in FCS (FCS-In) for LPS-induced DNA synthesis, FCS was fractionated by gel filtration chromatography using Sephacryl S-200, chromatography on DEAE-Sephacel, and affinity chromatography on heparin-Sepharose. FCS-In was eluted in the void volume peak from a Sephacryl S-200 column, indicating that FCS-In has a molecular weight of more than 250,000. The molecular weight of FCS-In was apparently 270,000 as determined by SDS-polyacrylamide gel electrophoresis (PAGE) under non-reducing conditions. Upon reduction, four components became detectable with apparent molecular weights of 170,000, 110,000, 67,000, and 30,000. The inhibitory activity in FCS-In material was inactivated by heat and trypsin treatment. The partially purified FCS-In inhibited LPS-induced DNA synthesis in BDM-1W3 cells, but did not inhibit the proliferation of BDM-1W3 cells induced by IL-3, granulocyte-macrophage CSF (GM-CSF), or macrophage CSF (M-CSF).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum-mediated modification of proliferation in factor-dependent macrophage cell lines. 829 98

Availability of mice with a targeted disruption of the interferon gamma (IFN-gamma) receptor gene (IFN-gamma R0/0 mice) made it possible to examine parameters of macrophage activation in the absence of a functional IFN-gamma receptor. We asked to what extent other cytokines could replace IFN-gamma in the induction of nitric oxide or major histocompatibility complex class II antigen (Ia) expression in peritoneal macrophages. In thioglycollate-elicited macrophages from wild-type mice, tumor necrosis factor (TNF) alone was virtually ineffective in inducing release of NO2- (the endproduct of nitric oxide generation), but TNF enhanced NO2- release in the presence of IFN-gamma. In macrophages from IFN-gamma R0/0 mice, which were unresponsive to IFN-gamma, TNF completely failed to stimulate NO2- release. The stimulatory actions of IFN-alpha/beta on NO2- release were indistinguishable in wild-type and IFN-gamma R0/0 macrophages: IFN-alpha/beta was ineffective on its own, showed marginal stimulation of NO2- release in combination with TNF, and was moderately effective in the presence of lipopolysaccharide. The level of constitutive Ia antigen expression was not significantly different in peritoneal macrophages from wild-type and IFN-gamma R0/0 mice. An increased Ia expression was induced by IL-4 and granulocyte-macrophage colony-stimulating factor in both wild-type and IFN-gamma R0/0 macrophages, but the magnitude of this induction was less than with optimal concentrations of IFN-gamma in macrophages from wild-type mice. IFN-alpha/beta showed only a minor stimulatory effect on Ia expression in both wild-type and IFN-gamma R0/0 macrophages. Simultaneous treatment of wild-type macrophages with IFN-alpha/beta and IFN-gamma reduced the IFN-gamma-induced Ia expression in wild-type macrophages, but IFN-alpha/beta did not show an inhibitory effect on IL-4- or granulocyte-macrophage-colony-stimulating factor-induced Ia expression in either wild-type or IFN-gamma R0/0 macrophages. The important role of IFN-gamma in the regulation of the induced expression of major histocompatibility complex class II antigen was confirmed by showing that after systemic infection with the BCG strain of Mycobacterium bovis resident peritoneal macrophages from IFN-gamma R0/0 mice had a lower level of Ia expression than macrophages from wild-type mice. The inability of other cytokines to substitute fully for IFN-gamma in macrophage activation helps to explain the earlier observed decreased resistance of IFN-gamma R0/0 mice to some infections.
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PMID:Generation of nitric oxide and induction of major histocompatibility complex class II antigen in macrophages from mice lacking the interferon gamma receptor. 834 79

In this present study we have characterized the array of hemopoietic cytokines generated by fibroblasts in response to inflammatory signals. It was shown that murine embryo fibroblasts (MEF) are able to generate colony stimulating factors (CSFs) [granulocyte-macrophage (GM-CSF), macrophage-CSF (CSF-1) and granulocyte-CSF (G-CSF)] as well as the hemopoietin interleukin 6 (IL-6), while the production of IL-3, IL-4 or tumor necrosis factor (TNF) could not be detected in MEF, as assessed by bioassays or expression of specific mRNA. The production of colony promoting activity was observed when fibroblasts were stimulated by lipopolysaccharide (LPS) or individual cytokines [IL-1, interferon-gamma (IFN-gamma), IL-2, IL-4 or TNF] in serum-free conditions as well as by serum itself. These inducers differentially stimulated in MEF the production of various CSFs; LPS induced mainly CSF-1, while cytokines or serum induced equivalent amounts of GM-CSF and CSF-1. The production of IL-6 was induced by LPS in serum-free conditions, while stimulation by cytokines (IL-1 or IFN-gamma) resulted in IL-6 production only in serum-supplemented cultures. Serum by itself did not induce IL-6 production by MEF. The secretion of IL-6 by fibroblasts was detected early and peaked after 6 hours, while CSF activity peaked after 24-72 hours, depending on the inducer. Constitutive mRNA expression of CSF-1 was detected in serum-free conditions in unstimulated MEF, however colony-promoting activity was detected only upon stimulation with cytokines, LPS or serum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Different regulatory levels are involved in the generation of hemopoietic cytokines (CSFs and IL-6) in fibroblasts stimulated by inflammatory products. 848 5


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