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)

Tumor necrosis factor-alpha (TNF-alpha) production by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral monocytes has been studied in 17 acute myeloid leukemia (AML) patients, 54 AML patients in complete remission (AML-CR), 9 acute lymphoblastic leukemia (ALL) patients and 13 ALL patients in complete remission (ALL-CR). TNF-alpha production by the unstimulated monocytes in ALL patients (n = 6, mean: 6.6 +/- 4.9 u/ml) was higher than that of normal controls (n = 13, 0.9 +/- 0.7 u/ml), AML patients (n = 14, 2.0 +/- 2.1 u/ml) and AML-CR patients (n = 21, 1.4 +/- 1.2 u/ml). TNF-alpha production by the LPS-stimulated monocytes of the AML-CR patients (n = 54, 12.4 +/- 13.4 u/ml) was significantly higher than that of the normal controls (n = 21, 3.5 +/- 2.5 u/ml) and the AML patients (n = 17, 2.6 +/- 2.4 u/ml), p < 0.01, but there were not any significant differences among the AML-CR patients and the ALL patients or the ALL-CR patients. We separated the AML-CR patients into 3 groups, depending on the length of their remission, and found that AML-CR patients with longer than 6 months (M) but less than 60 M (n = 21, 15.7 +/- 16.9 u/ml) and the patients with a remission longer than 60 M (n = 11, 18.2 +/- 15.9 u/ml) had significantly higher TNF-alpha production than that of the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The monocyte tumor necrosis factor-alpha production in patients with acute leukemia in complete remission. 134 64

Post-transfusional hepatitis is often a complication in patients with acute myelogenous leukemia (AML) in whom survival is paradoxically prolonged. The etiology is unknown. In previous studies, we showed that impaired hepatic endotoxin (lipopolysaccharide, LPS) clearance in patients with acute viral hepatitis A, B, or C versus controls results in endotoxemia and tumor necrosis factor alpha (TNF-alpha) release. TNF-alpha mediates anti-proliferative and differentiating effects in AML cell lines. Interferon-gamma (IFN-gamma) released in acute viral hepatitis, acts in synergy with TNF-alpha. HL60, KG1, and U937 AML cells treated 3, 6, and 9 days with physiologically attainable TNF-alpha (10 U/ml), IFN-gamma (100 U/ml) and LPS (10 ng/ml) levels, have significantly diminished viability and cell growth versus controls. Treatment of HL60 AML cells with LPS/TNF-alpha/IFN-gamma also resulted in significantly increased monocytic pathway differentiation not seen with KG1 or U937 AML cells. HL60 AML cells treated with TNF-alpha/IFN-gamma for 6 days released endogenous TNF-alpha (1.57 U/10(6) cells) upon LPS stimulation compared to less than 0.01 U/10(6) cells in non-LPS-stimulated TNF-alpha/IFN-gamma-treated cells or untreated cells (p less than 0.0001). Untreated HL60 AML cells co-cultured with HL60 cells pretreated for 6 days with TNF-alpha/IFN-gamma and then subjected to LPS stimulation had significantly diminished cell growth compared to controls (p less than 0.0001). This effect could be reversed with anti-TNF-alpha antibody, supporting the concept that endogenous TNF-alpha release by LPS/TNF-alpha/IFN-gamma treated HL60 AML cells may act by paracrine means to suppress growth of other AML cells. The beneficial effects of post-transfusional hepatitis in AML patients may be mediated via LPS/TNF-alpha/IFN-gamma-induced AML cell growth suppression and/or terminal differentiation in which AML cells participate by releasing TNF-alpha after being acted upon by LPS/TNF-alpha/IFN-gamma. Endogenously released TNF-alpha might then act by autocrine/paracrine means to mediate further suppression and terminal differentiation.
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PMID:Beneficial effects of post-transfusional hepatitis in acute myelogenous leukemia may be mediated by lipopolysaccharides, tumor necrosis factor alpha and interferon gamma. 140 56

The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines.
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PMID:Growth restraint and differentiation by LPS/TNF-alpha/IFN-gamma reorganization of the microtubule network in human leukemia cell lines. 160 11

Human T cell hybridomas were constructed by somatic cell fusion in order to dissect molecular heterogeneity of human macrophage activating-factors (MAF). Two stable human hybridoma supernatants contained MAF activity capable of inducing human monocytes tumoricidal without the help of bacterial lipopolysaccharide (LPS). These supernatants in the presence of LPS could also render mouse macrophages tumoricidal. In contrast, recombinant and natural human interferon-gamma (Hu-IFN-gamma) activated human monocytes, but not mouse peritoneal macrophages. The supernatants from the two clones could neither support the growth of human-granulocyte-macrophage colony stimulating factor/human-interleukin-4-dependent (Hu-GM-CSF/Hu-IL-4) cell lines, such as AML 193 and TALL-101, nor stimulate the proliferation of human-interleukin-2-dependent human cell line and lectin-stimulated lymphoblast, which are responsive to human-interleukin-2 and human-interleukin-4. Rabbit or murine antibodies against human-interferon-gamma (Hu-IFN), human-granulocyte-macrophage colony stimulating factor, human interleukin-1 alpha, human-interleukin-1 beta, human-interleukin-6, human-tumour necrosis factor (Hu-TNF), human-lymphotoxin and human-macrophage migration inhibitory factor (Hu-MIF) could not absorb MAF activity. MAF activity in the hybridoma supernatants is associated with the two polypeptides of molecular weights of 70,000-80,000 and 20,000-30,000 daltons, as determined by gel filtration. These results indicate decisively that novel MAF molecule(s) is secreted by human T cell hybridomas.
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PMID:Constitutive production of novel macrophage-activating factor(s) by human T cell hybridomas. 212 37

1. Induction of tumor cell differentiation could reverse transformed cells into normal, mature cells. Important question is whether these malignant-to-normal reversed cells are really normal ones. 2. We have developed an experimental model based on the examination of three different levels of human acute myeloid leukemia cell properties before and after induction of differentiation: morphological (percentage of undifferentiated blast cells), functional (DNA ploidy, Fc receptors, phagocytic activity, clonogenic assay in soft agar, oxidative metabolism which accompanies phagocytosis in mature granulocytes) and genetical (expression of oncogene p53). 3. Several inducers have been employed: dimethylsulfoxide (DMSO) granulocyte-macrophage colony stimulating factor (GM-CSF); tunicamycin, interferon gamma, tumor necrosis factor and lipopolysaccharide. 4. Our results indicate that the reversion of leukemic cells into mature normal ones with some inducers (DMSO, GM-CSF) could be a complete process.
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PMID:Artificial reversion of acute myeloid leukemia cells into normal phenotype. 218 58

A prototypic "immediate early" gene, c-fos, has been extensively investigated in relation to the differentiation and activation of myelomonocytic cells. The c-fos gene product is associated in transcriptional complexes with the c-jun product. These protooncogenes are part of the regulatory network of gene expression. The present study was designed to investigate expression of the c-jun protooncogene in human circulating myelomonocytic cells. We found that c-jun is constitutively expressed in normal monocytes and granulocytes, whereas low levels of transcripts are found in lymphocytes. Acute myelogenous leukemia (AML) samples of French-American-British Cooperative Group (FAB) subtypes 1 through 4 express appreciable levels of this protooncogene. Normal phytohemagglutinin (PHA)-activated lymphocytes express high levels of c-jun. Expression in normal myelomonocytic cells is detectable even after 18 hours of culture. The c-jun transcripts in myelomonocytic cells have a half-life of approximately 20 minutes and are superinduced by cycloheximide, which affects both the degradation rate of mRNA and the transcriptional activity of the c-jun gene. Functional activation of monocytes and granulocytes with phorbol esters, lipopolysaccharide, and tumor necrosis factor (TNF) increase c-jun expression. This induction is rapid, transient, and does not require intervening protein synthesis. Runoff experiments showed that in freshly isolated untreated monocytes, the c-jun gene is constitutively transcribed, and that induction by lipopolysaccharide is at least in part at the transcriptional level. Moreover, lipopolysaccharide (LPS) treatment reduced the degradation rate of c-jun transcripts, prolonging the half-life to approximately two hours. Expression of c-jun in resting and activated monocytes and granulocytes suggests that this protooncogene may play a role in the differentiation and activation of cells belonging to the myelomonocytic lineage.
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PMID:Expression of c-jun protooncogene in human myelomonocytic cells. 247 86

A continuous tissue culture cell line (Karpas line 120), derived from a patient with acute myeloblastic leukemia, not only demonstrates myeloblastic morphology and in vitro expression of several myeloid-specific biochemical markers but also contains Epstein-Barr virus (EBV) nuclear antigen. The present studies demonstrate EBV-genome-specific DNA within the total cellular DNA by molecular hybridization, thus establishing the presence of stable viral genome integration. The cells demonstrate complex coordinated myeloid functions including ingestion, degranulation, and respiratory burst activity. Line 120 cells show a respiratory burst (superoxide and hydrogen peroxide generation and hexosemonophosphate shunt activity) in response to soluble (phorbol myristate acetate) and particulate (latex beads) stimuli, as do normal granulocytes. They ingest complement-opsonized particles (lipopolysaccharide-oil droplets, zymosan, and bacteria), and degranulate in response to them. However, unlike normal granulocytes, the line 120 cells do not demonstrate respiratory burst activity in response to these complementopsonized particles. The dissociation between ingestion of complement-opsonized particles and activation of oxygen-dependent bactericidal activity severely impairs bacterial killing as compared with normal polymorphonuclear phagocytes.
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PMID:Dissociation of opsonized particle phagocytosis and respiratory burst activity in an Epstein-Barr virus-infected myeloid cell line. 624 64

Studies on the effect of retinoic acid (RA) and 1,25-dihydroxyvitamin (D3) on the differentiation of leukemic cells have provided insight into the cellular and molecular mechanisms underlying hematopoietic cell differentiation. We have evaluated the combined effect of these chemical inducers on the differentiation of HL-60 and AML-193 promyelocytic leukemia cell lines. Simultaneous RA+D3 addition potentiated leukemic cell maturation up to mature phagocytic cells. Interestingly, AML-193 cells induced with D3 and RA displayed a typical neutrophilic morphology while exhibiting properties specific to monocytic cells, e.g., high expression of CD14 membrane antigen, capacity to bind bacterial lipopolysaccharide, and monocytic-specific esterase activity; this hybrid granulomonocytic (GM) phenotype was not observed upon initial incubation with one inducer and later addition of the other. Parallel control studies were performed with purified normal GM progenitors, triggered by interleukin 3+GM-colony-stimulating factor (CSF) in FCS-rich or -free clonogenic culture, by GM-CSF+M-CSF in FCS-rich clonogenic culture, and by M-CSF in liquid suspension culture. The progenitors grown in the first condition generate exclusively G clones, even upon addition of D3 and/or RA. The progenitors grown in the second and third culture conditions generate either G and M clones (second culture condition) or a population of cells composed by a majority of monocytes (third culture condition); the D3 addition did not modify this differentiation pattern, whereas RA or RA+D3 addition elicited a marked inhibition of monocytic differentiation. These observations suggest that the development of a hybrid GM phenotype is restricted to the progeny of bipotent GM leukemic precursors.
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PMID:Combined vitamin D3/retinoic acid induction of human promyelocytic cell lines: enhanced phagocytic cell maturation and hybrid granulomonocytic phenotype. 764 32

The ability of peripheral blood leukocytes (PBL) of 13 selected patients with acute myeloid leukemia (AML), and of 10 healthy subjects to produce interferon (IFN) spontaneously and after in vitro induction was tested. Spontaneous IFN production was detected in supernatants of PBL cultures of healthy subjects but was not present in cultures of leukemic cells (leukocytes density 1 x 10(6) ml). After induction with Newcastle disease virus (NDV) PBL cultures from 5 patients with AML exhibited a low IFN response, while in others IFN titers were similar to controls. The IFN titers induced with lipopolysaccharide (LPS) were lower in leukemic cells than those detected in control cells. The absence or low IFN levels after induction with phytohemagglutinin (PHA) correlated with very small numbers of normal lymphocytes in blood of leukemic patients.
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PMID:Interferon production by peripheral blood leukocytes of patients with acute myeloid leukemia. 891 15

MONO-MAC-1 is a human cell line with properties of blood monocytes, which can be used as a model system to study monocytic functions in vitro. In the present study, we prepared a karyotype of MONO-MAC-1, analysed the growth behaviour, determined the presence of differentiation-associated antigens and studied the expression and secretion of several cytokines upon stimulation with 12-O-tetradecanoyl phorbol 13-acetate (TPA) and lipopolysaccharide (LPS). The MONO-MAC-1 cells have a near diploid karyotype and contain several recurrent chromosomal rearrangements, in particular the translocation (9;11) commonly found in AML-M5. Stimulation with TPA or LPS induced changes in morphology and gene expression, especially an increase in the level of the differentiation marker CD14 and the production of monocyte-related cytokines. Both biomodulators alone were sufficient to promote TNF alpha release; however, the combination of TPA and LPS resulted in a synergistic increase of TNF alpha secretion. Northern blot analysis indicated that upregulated production of TNF alpha was due to induced synthesis of mRNA. The mRNA accumulation peaked approximately 2 h after stimulation and maximum levels of TNF alpha were found in the supernatants after 4-8 h of culture. The MONO-MAC-1 cells could not be restimulated with the same inducer to release TNF alpha when a 48 h pre-treatment was carried out with LPS or TPA. LPS induced the release of granulocyte colony-stimulating factor (G-CSF), while TPA failed to do so. Vice versa, secretion of macrophage CSF (M-CSF) could be induced by TPA, but not by LPS. However, LPS enhanced the TPA-induced M-CSF production. Similarly, incubation of MONO-MAC-1, simultaneously with TPA and LPS, led to granulocyte macrophage CSF (GM-CSF) and interleukin-1beta (IL-1beta)secretion, while both stimulators alone had almost no (TPA) or only a weak (LPS) effect on the secretion of GM-CSF and IL-1beta. Our results demonstrate that MONO-MAC-1 is a unique cell line with distinct monocytic features; certain monocytic properties can be upregulated by activation of intracellular signalling pathway(s). We suggest that, besides the LPS receptor CD14, activation of PKC participates in these process, especially in the production and secretion of cytokines by MONO-MAC-1 cells.
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PMID:A model system in haematology and immunology: the human monocytic cell line MONO-MAC-1. 915 Mar 50


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