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)

Human cytomegalovirus (CMV) infection is often associated with myelosuppression and acute inflammatory reaction in immunocompromised patients. We have previously documented that CMV exposure of bone marrow (BM) stromal cells reduces the capacity of these cells to support hematopoiesis because of a decreased production of colony-stimulating factors. This study examines the potential role of CMV on constitutive and lipopolysaccharide (LPS)-stimulated production of cytokines involved in inflammatory reaction, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) by BM stromal cells. The release of IL-6 was already detectable 2 hours post CMV-infection (2.5-fold increase in production) and the cumulative production of IL-6 after 5 days of infection was 23 +/- 1.2 ng/mL (ninefold increase in production). CMV was also able to induce a time-dependent production of LIF that was maximal 8 hours after CMV infection (2.5-fold increase in production). Concomitantly, there was no detectable release of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) by CMV-infected stromal cells. The similar IL-6 and LIF production in the presence of polymyxin B ruled out the possibility that this increase could be caused by contamination of the viral stock by endotoxin. In addition, ultraviolet-inactivated virus behaved similarly to live virus and caused the release of IL-6 and LIF. However, heat-inactivated CMV was unable to induce IL-6 and LIF secretion by BM stromal cells. The production of IL-6 and LIF was also evaluated after stimulation by LPS. After 5 days of CMV exposure, the LPS-stimulated production of IL-6 and LIF was significantly lower than uninfected controls. This LPS-induced release of cytokine production was found to be dependent of viral replication. The experiments have shown that CMV is a potent inducer of IL-6 and LIF with differential effect on constitutive and LPS-stimulated cytokine production by stromal cells; we suggest that CMV induction of IL-6 and LIF during the first hours of infection could play a role in CMV-induced inflammatory reaction. Moreover, our results show that human CMV can disturb the balanced cytokine network involved in the regulation of hematopoiesis.
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PMID:Human cytomegalovirus increases constitutive production of interleukin-6 and leukemia inhibitory factor by bone marrow stromal cells. 854 77

A panel of two poorly differentiated (HA22T/VGH and SK-Hep-1) and six well-differentiated (HuH-6-cl 5, HuH-7, PLC/PRF/5, Hep G2, Hep 3B, and Tong) human hepatocellular carcinoma (HCC) cell lines were studied for the production of colony-stimulating factors (CSFs) using the granulocyte and macrophage colony formation (CFU-GM) assay, immunocytochemical staining, and Northern blotting. Medium conditioned by untreated HA22T/VGH cells contained a high level of CSFs that could stimulate the in vitro colony formation of human myeloid progenitor cells. The HA22T/VGH cell-derived CSF had an apparent molecular weight of 23 kD. Its activity could be effectively neutralized by antiserum against granulocyte-macrophage CSF (GM-CSF) but not by antibodies to other hematopoietic growth factors, including G-CSF, M-CSF, interleukin-3 (IL-3), and IL-6. Correspondingly, immunocytochemical studies using monoclonal anti-GM-CSF showed a strong positive reaction in the cytoplasm of the HA22T/VGH cells. Northern blot analysis revealed that untreated HA22T/VGH cells expressed a considerable amount of GM-CSF mRNA, confirming that GM-CSF production was constitutive. At optimal concentrations, lipopolysaccharide (LPS), IL-1beta, interferon-gamma (IFN-gamma), and tumor-promoting phorbol diester (TPA) could all stimulate HA22T/VGH cells to secrete GM-CSF. In addition to HA22T/VGH, SK-Hep-1 cells could also produce GM-CSF, although less effectively, whereas all the well-differentiated HCC cell lines tested were negative for CSF production. Morphologic, cytochemical, and immunocytochemical examinations demonstrated that both poorly differentiated CSF-producing HCC cell lines (HA22T/VGH and SK-Hep-1) were macrophage-like in morphology, possessed nonspecific esterase (NSE) activity, and expressed CD14, CD68, and HLA-DR on their surface, while all the well-differentiated HCC cell lines were epithelioid and lacked myeloid differentiation antigens. These results suggest that monocytoid features and CSF production may be differentiation markers of hepatocytes at the immature stages, amd that the HA22T/VGH and SK-Hep-1 cell lines may be valuable tools for the study of hepatic function and differentiation.
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PMID:Constitutive production of colony-stimulating factors by human hepatoma cell lines: possible correlation with cell differentiation. 859 73

Tumor necrosis factor-alpha (TNF alpha) is a biologically active cytokine with a wide range of functions, which is primarily expressed by macrophages. It is produced as a biologically active propeptide that becomes processed to the mature form of secreted protein. Previous studies used a mouse macrophage cell line and showed that after stimulation with lipopolysaccharide, TNF alpha propeptide is expressed as multiple isoforms with approximate molecular masses of 26, 29 and 32 kDa. However, little is known of the production of TNF alpha isoforms from normal macrophages or of the effects of cytokines on TNF alpha production by macrophages in the absence of co-stimulation by lipopolysaccharide. We have compared the TNF alpha isoforms produced by cytokine-and lipopolysaccharide-stimulated bone marrow-derived macrophages from mice that normally respond to lipopolysaccharide (C3H/HeN) and mice that are hyporesponsive (C3H/HeJ). We found that the pattern of immunoprecipitated TNF alpha propeptide isoforms expressed depended on the stimulus: lipopolysaccharide, granulocyte-macrophage colony-stimulating factor or macrophage colony-stimulating factor. Lipopolysaccharide induced three isoforms of 25, 29 and 35 kDa, supporting previous studies. However, macrophage and granulocyte-macrophage colony-stimulating factors also stimulated cells to express the 24 and 27 kDa isoforms, but not the 35 kDa isoform. In addition, cells stimulated with granulocyte-macrophage colony-stimulating factor expressed a novel 20 kDa propeptide. The results show that granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor and lipopolysaccharide differently regulate TNF alpha protein expression and suggest that different isoforms may have different functions.
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PMID:Differential expression of tumor necrosis factor-alpha isoforms from lipopolysaccharide- and cytokine-stimulated mouse macrophages. 881 44

Secondary macrophage cell cultures were generated from the primary culture of epiblasts of 8-d-old pig blastocysts. The epiblast-derived macrophagelike (EDM) cells have a morphology and ameboid behavior that is typical of tissue histocytes. The cells reacted positively with monoclonal antibodies specific for pig granulocyte-macrophage lineage cells, and were not reactive with monoclonal antibodies specific for pig B and T lymphocytes. Marked phagocytic behavior and the formation of phagosomes were demonstrated following incubation with FITC-labeled bacteria. The EDM cells stained positively for nonspecific acid esterase that was not inhibited by sodium fluoride. DiI-acetylated-LDL was rapidly taken up by the cells. Transmission electron microscopy of the EDM cells showed phagolysosomes, numerous cytoplasmic vacuoles, large, lobed nuclei, and numerous pseudopods or filopodia at the cell surface. Strong reactivity of the cells with anti-CD14 monoclonal antibody was observed. Further, cytotoxic activity was produced from the EDM cells after exposure to lipopolysaccharide in a concentration and time-dependent manner. The cultures could be maintained and expanded for several months on STO co-culture. Their derivation from the epiblast of the pig demonstrates the possibility of obtaining hemopoietic cell cultures from the preimplantation blastocysts of all mammals.
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PMID:Continuous cultures of macrophages derived from the 8-day epiblast of the pig. 894 26

It is well known that adherence of monocytes (MO) to extracellular matrix substrates or tissue culture plastic activates these cells and induces the expression of a multitude of genes. Especially, it was described, that MO are primed by cell adhesion to produce higher amounts of some cytokines, e.g. interleukin (IL)-8 and tumor necrosis factor alpha (TNF-alpha). In order to investigate adherence-induced effects upon cytokine production, we seeded MO into tissue cultures and stimulated cells by lipopolysaccharide (LPS) simultaneously or at later time points. An increasing time-lag between cell adhesion and LPS-stimulation led to differential effects upon cytokine production: whereas TNF was upregulated (in accordance with reports by others), granulocyte colony-stimulating factor (G-CSF) was considerably down-regulated. In contrast, G-CSF production did not change, when cells were kept under non-adherent conditions in whole blood. In adherent cultures down-regulation of G-CSF could already be observed after two hours with a maximum after 24 h and was paralleled by a much lower abundance of G-CSF mRNA. Adhesion induced a significant suppression of G-CSF comparable to MO, if mature macrophages derived from MO in vitro were examined. Furthermore, two other cytokines, granulocyte-macrophage (GM)-CSF and IL-6, were also down-regulated following adhesion. In conclusion, activation of mononuclear phagocytes by adhesion can lead to "priming" for the production of some cytokines and at the same time to "silencing" for the production of others.
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PMID:Differential effects of cell adherence on LPS-stimulated cytokine production by human monocytes and macrophages. 914 30

Hemorrhagic shock induces tissue hypoxia and has been demonstrated to alter the myelopoietic response to bacterial lipopolysaccharide (LPS). Interleukin-1 and interleukin-6 are important mediators of immunologic events after hemorrhagic shock. Bone marrow stroma release inflammatory cytokines, which may play a role in the regulation of myelopoiesis after injury. The aim of this study was to correlate cytokine gene expression with protein release and myelopoiesis by total bone marrow cells. The role of bone marrow stroma after exposure to hypoxia and lipopolysaccharide was also examined. BALB/c mice were designated as normoxia or hypoxia and total bone marrow cells were harvested. Hypoxia mice were exposed to 2 h of 5% O2/95% N2, and then returned to room air. Additional groups of mice were given LPS intraperitoneally. Bone marrow stroma, from BALB/c mice, was similarly designated. Myelopoiesis was assessed by growth of granulocyte-macrophage progenitor cells (CFU-GM). Interleukin-1 and interleukin-6 protein activity was assessed by bioassay. RNA was extracted from both total bone marrow cells and bone marrow stroma. By day 5, LPS alone resulted in a 93% increase in CFU-GM versus normoxia. Hypoxia and LPS exposure significantly decreased CFU-GM on days 1, 3, and 5. LPS alone induced an increase in interleukin-6. At 2, 6, and 24 h, hypoxia blunted interleukin-6 release in response to LPS. Hypoxia alone could not induce interleukin-6. However, hypoxia did induce interleukin-1 mRNA without the release of bioactive protein. In the remainder of groups, interleukin-1 protein levels and mRNA levels were correlated. Bone marrow stroma interleukin-1 and interleukin-6 protein activity was consistently correlated with that of total bone marrow. These data demonstrate that bone marrow cytokine production is differentially regulated by hypoxia. Hypoxia impairs interleukin-6 protein and mRNA in response to LPS, which may play a role in the suppression of myelopoiesis after shock. Also, bone marrow stroma plays an integral role in regulating myelopoiesis.
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PMID:Differential effects of acute hypoxia and endotoxin on the secretion and expression of bone marrow interleukin-1 and interleukin-6. 916 66

Shigella, the etiological agent of bacillary dysentery, rapidly kills human monocyte-derived macrophages in vitro. Wild-type Shigella flexneri, but not a nonvirulent derivative, induced human macrophage apoptosis as determined by morphology and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL). Shigella-mediated macrophage cell death was blocked by the peptide inhibitors of caspases, acetyl-Tyr-Val-Ala-Asp-aldehyde (acetyl-YVAD-CHO) and acetyl-Tyr-Val-Ala-Asp-chloromethylketone (acetyl-YVAD-CMK). Protection from apoptosis by YVAD was observed in monocytes matured in the presence or absence of colony-stimulating factors (CSF) like macrophage-CSF or granulocyte-macrophage-CSF. Furthermore, lipopolysaccharide (LPS) or gamma interferon (IFN-gamma) rendered human macrophages partially resistant to Shigella cytotoxicity. Macrophages stimulated with either LPS or IFN-gamma were also protected by YVAD from Shigella-induced cell death. During Shigella infections of human macrophages, interleukin-1beta (IL-1beta) was cleaved to the mature form. IL-1beta maturation was severely retarded by YVAD, indicating that IL-1beta-converting enzyme (ICE; caspase 1) is activated in Shigella-induced apoptosis. The finding that Shigella induces apoptosis in human macrophages by activating ICE supports the hypothesis that the acute inflammation characteristic of shigellosis is initially triggered by apoptotic macrophages which release mature IL-1beta during programmed cell death.
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PMID:The interleukin 1beta-converting enzyme, caspase 1, is activated during Shigella flexneri-induced apoptosis in human monocyte-derived macrophages. 939 11

IL-12 is important for Th1 differentiation. Myeloid-derived antigen-presenting cells (APC) such as monocytes, macrophages (Mphi) and dendritic cells (DC) are believed to be major sources of IL-12 in vivo. We have compared IL-12 production of fresh monocytes with Mphi differentiated in vitro using macrophage colony-stimulating factor (M-CSF) or human plasma, and in vitro generated dendritic cells, since these differentiated cell types represent APC at sites of antigen challenge. Macrophages stimulated with lipopolysaccharide (LPS) or heat-killed Listeria monocytogenes in the presence or absence of IFN-gamma produced minimal IL-12 p70 by comparison with DC or monocytes, despite comparable production of TNF-alpha. M-CSF-induced Mphi produced low levels of IL-10 constitutively and high levels after stimulation with LPS, but neutralization of IL-10 did not augment Mphi IL-12 production. Exposure of Mphi to TNF-alpha, granulocyte-macrophage CSF or IFN-gamma did not substantially up-regulate IL-12. Therefore M-CSF induces a differentiated Mphi phenotype in which IL-12 production is down-regulated, perhaps irreversibly. This may be the default pathway for monocyte-Mphi development in the absence of inflammation.
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PMID:Human macrophages induced in vitro by macrophage colony-stimulating factor are deficient in IL-12 production. 971 Feb 27

Dendritic cells (DC) can be generated by culture of adherent peripheral blood (PB) cells in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). There is controversy as to whether these DC arise from proliferating precursors or simply from differentiation of monocytes. DC were generated from myeloid-enriched PB non-T cells or sorted monocytes. DC generated from either population functioned as potent antigen-presenting cells. Uptake of [3H]-thymidine was observed in DC cultured from myeloid-enriched non-T cells. Addition of lipopolysaccharide or tumor necrosis factor-alpha led to maturation of the DC, but did not inhibit proliferation. Ki67(+) cells were observed in cytospins of these DC, and by double staining were CD3(-)CD19(-)CD11c-CD40(-) and myeloperoxidase+, suggesting that they were myeloid progenitor cells. Analysis of the starting population by flow cytometry demonstrated small numbers of CD34(+)CD33(-)CD14(-) progenitor cells, and numerous granulocyte-macrophage colony-forming units were generated in standard assays. Thus, production of DC in vitro from adherent PB cells also enriches for progenitor cells that are capable of proliferation after exposure to GM-CSF. Of clinical importance, the yield of DC derived in the presence of GM-CSF and IL-4 cannot be expanded beyond the number of starting monocytes.
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PMID:Proliferation in monocyte-derived dendritic cell cultures is caused by progenitor cells capable of myeloid differentiation. 971 87

Leustroducsin B (LSN-B), a novel colony-stimulating factor (CSF) inducer, has been shown to have various biologic activities in vivo. To compare the CSF-inducing activity of LSN-B in vitro with that of the well-known cytokine inducer, interleukin-1beta (IL-1beta), bacterial lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA), we measured granulocyte (G)-CSF and granulocyte-macrophage (GM)-CSF levels that were induced with the stimuli in several mesenchymal cells. The results indicated that each stimulant displayed a different profile in the induction of G-CSF and GM-CSF. Next, to investigate if LSN-B induces cytokines other than G-CSF and GM-CSF, we characterized cytokines that were induced with LSN-B from bone marrow stromal cells (BMSCs). The results showed that a variety of cytokines, including G-CSF and GM-CSF, were induced in both clonal and primary BMSCs. From these results, we speculate that LSN-B induces cytokine production via a regulatory pathway distinct from that of IL-1beta, LPS, or PMA and that this signaling of LSN-B might lead to the production of a variety of cytokines in BMSCs. In addition, from our in vitro and in vivo results, we speculate that the biologic activities of LSN-B in vivo might be based on its own cytokine-inducing activity even though the target cell type of LSN-B in vivo remains to be determined.
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PMID:The effect of leustroducsin B on the production of cytokines by human mesenchymal cells. 980 22


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