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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three human monocytic cell lines, U-937, THP-1 and Mono Mac 6 have, because of their morphology and staining properties, been classed as cell lines frozen in a window of the monocyte differentiation lineage corresponding to monoblasts and/or immature monocytes. These cell lines were analyzed for expression of a panel of hematopoietic differentiation markers by Northern blot analysis. They were all found to express one or several biochemical markers characteristic of immature cells in monocytic development, including myeloperoxidase, N-elastase, cathepsin G, myeloblastin, and azurocidin. Normal peripheral blood monocytes did not express these markers. Moreover, several markers expressed at high levels in mature monocytes, such as lysozyme, CD14, MHC class II and alpha-1 antitrypsin were either not expressed or were expressed only at low levels in the three cell lines analyzed. These results show that arrested differentiation at a relatively early stage of monoblast development is a common denominator for these human monocytic cell lines. Thus, transforming mutations acting at such an immature differentiation stage may frequently lead to neoplastic transformation, whereas similar mutations occurring at a more mature differentiation stage never give rise to any leukemias due to the loss of proliferative potential in committed cells.
Leukemia 1994 Sep
PMID:Human cell lines U-937, THP-1 and Mono Mac 6 represent relatively immature cells of the monocyte-macrophage cell lineage. 809 34

The beta-adrenergic receptor, its occupancy and subsequent modulation of intracellular cAMP, and mRNA expression were characterized for the promonocytic leukemia cell line THP-1. We report that THP-1 cells appear to express a beta-1 receptor with a Kd of 1.8 +/- 0.3 x 10(-11) microM and a B max of 108 +/- 0.07 fmole/mg protein using 125I-iodocyanopindolol (125I-ICYP). The potency of various beta-adrenergic agonists to compete for the 125I-ICYP binding site followed the order: isoproterenol (0.8 microM) > dobutamine (2.1 microM) > salbutamol (3 microM) > epinephrine (3.8 microM) > soterenol (4.6 microM) > terbutaline (11.1 microM) > norepinephrine (13.8 microM). Occupancy of the beta receptor on THP-1 cells results in activation of adenyl cyclase suggesting that these cells have a functional beta-adrenergic receptor. This receptor also has specific immunoregulatory properties, reducing message levels for tumor necrosis factor--but not interleukin 1, following treatment with isoproterenol (approximate EC-50 of 0.01 microM). We conclude, based on the above criteria, that THP-1 cells express a beta-1 receptor which, following ligand binding, results in increased cAMP leading to downregulation of TNF expression.
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PMID:Molecular pharmacology of the beta-adrenergic receptor on THP-1 cells. 809 34

We studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules by expressing an antisense RNA of poly(ADP-ribose) synthetase. We constructed two expression plasmids capable of expressing an antisense RNA for poly(ADP-ribose) synthetase, carrying 0.7-kilobase long fragment of 5'-coding region (pAS-5') and full-length cDNA (pAS-FL) of poly(ADP-ribose) synthetase in an antisense orientation under control of metallothionein I promoter. We transfected the plasmid into human leukemia THP-1 cells and isolated transformants. Metal-inducible reduction in poly(ADP-ribose) synthetase activity was observed in two pAS-5'-transfected clones out of 72 neo-resistant clones examined, and metal-independent reduction in the activity was exhibited in pAS-FL-transfected clones. The antisense RNA was induced in a metal-dependent manner in the clones transfected with pAS-5', as judged by hybridizing with a sense riboprobe of the synthetase gene. The mRNA of the synthetase decreased 1 day after an addition of metal ions, and the synthetase activity of the transformants decreased by more than 90% 3 days after an addition of metal ions. Thus, we incubated the transformant clones in the presence of metal ions for 3 days and then treated them with IFN-gamma. The IFN-gamma-inducible expression of MHC class II molecules was amplified in the transformant clones, as judged by RNA blot analysis and flow cytometry. These results indicate that the decrease in poly(ADP-ribose) synthetase makes THP-1 cells favorable to induce MHC class II molecules by IFN-gamma.
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PMID:Enhancement of interferon-gamma-induced major histocompatibility complex class II gene expression by expressing an antisense RNA of poly(ADP-ribose) synthetase. 811 88

The in-vitro activity of a group of antifungal compounds known to inhibit ergosterol synthesis was investigated against Leishmania donovani grown as intracellular amastigotes in the human leukaemia monocyte cell line, THP-1. Toxicity on the host cells was assessed using the colorimetric MTT assay. Compounds inhibiting 2,3 oxidosqualene lanosterol cyclase; RO 43-3815, RO 43-5955, RO 43-8208, RO 42-6589 and RO 43-0688 displayed high activity with a median effective dose (ED50) of 0.6, 0.9, 3.5, 2.2 and 0.7 mg/L respectively. Of the azole compounds, oxiconazole had an ED50 value of 3.3 mg/L while ketoconazole showed the least activity. The delta-14-reductase and delta-8-delta-7 isomerase inhibitor, amorolfine, gave the highest therapeutic index with an ED50 value of 1.6 mg/L. Most compounds tested had a lower ED50 value than the standard antileishmanial drugs, sodium stibogluconate (5.5 mg Sbv/L) and meglumine antimoniate (3.0 mg Sbv/L) indicating the clean potential of these antifungal compounds in treating leishmaniasis.
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PMID:The in-vitro anti-leishmanial activity of inhibitors of ergosterol biosynthesis. 814 23

The effect of monocyte colony stimulating factor (M-CSF) on the beta-very low density lipoprotein (beta-VLDL) metabolism in THP-1 cells (human leukemia cell line) was studied. THP-1 cells treated with M-CSF decreased Latex Bead phagocytosis, but the cells incubated with 12-tetradecanoyl-phorbol-13-acetate (TPA) enhanced phagocytosis 2.5-fold. Binding activity of 125I-M-CSF to THP-1 cells was higher than that in THP-1 cells elicited with TPA. THP-1 cells incubated with M-CSF before TPA treatment were designated MT macrophages, and those incubated with M-CSF after TPA treatment were called TM macrophages. When these cells were incubated with beta-VLDL, the cholesterol ester content in MT macrophages was less than in TM macrophages. The uptake of [3H]cholesterol oleate-beta-VLDL in MT macrophages was the same as in TM macrophages. The released radioactivity from [3H]cholesterol oleate-beta-VLDL loaded MT macrophages was higher than that from TM macrophages. Acid cholesterol esterase activity and ACAT activity were the same in both types of macrophages. Neutral cholesterol esterase activity was higher in MT than in TM macrophages. These results suggested that beta-VLDL-induced cholesterol ester deposition in THP-1 cells-derived macrophages was suppressed by M-CSF, when M-CSF acted at the stage of monocytes (THP-1 cells), and that the reduction of cholesterol ester might be due to enhanced release of cholesterol from the cells with high neutral cholesterol esterase activity.
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PMID:Impact of monocyte colony-stimulating factor upon beta-very low density lipoprotein (beta-VLDL) cholesterol metabolism in tetradecanoyl phorbol acetate-derived THP-1 cells. 819 98

Protein kinase C (PKC)-activating phorbol esters are known to induce the expression of several genes in monocytic cells. As the effect of serine-threonine kinases, such as PKC, is often counteracted by specific protein phosphatases, we have now examined the role of phosphatases in the regulation of the phorbol ester (PMA)-induced interleukin-1 beta (IL-1 beta) gene expression in the THP-1 monocytic leukaemia cell line. Okadaic acid (OA) is a potent tumour promoter, the function of which is based on its activity to inhibit the serine/threonine specific phosphatases 1 and 2A (PP1 and PP2A, respectively). Thus, it mimicks or potentiates the action of PKC activators in several cell types. Our data demonstrate that alone OA induced a very weak expression of IL-1 beta mRNA, but it strongly enhanced the PMA-induced IL-1 beta expression. To analyse the site of action of OA, the cells were transiently transfected with a chloramphenicol acetyl transferase (CAT)-reporter plasmid containing the AP-1 binding site as the enhancer. Alone, OA was a weak inducer of CAT-activity in these cells, but again it strongly enhanced the PMA-induced response. Similar data were obtained with cells transfected with a reporter plasmid containing the PMA-responsive element (containing a putative AP-1 binding site) of the IL-1 beta gene. Thus, these data indicate that the PMA-induced AP-1 enhancer activity, which is required for the expression of the IL-1 beta gene, is controlled in these cells by PP1 and/or PP2A. As OA did not synergize with PMA in the induction of expression of genes encoding the AP-1 proteins (c-fos, c-jun, junB), it is likely that OA potentiates the AP-1 enhancer activity by its effect on protein phosphorylation.
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PMID:Okadaic acid, a phosphatase inhibitor, enhances the phorbol ester-induced interleukin-1 beta expression via an AP-1-mediated mechanism. 825 16

We examined the ability of hematopoietic cells to transactivate the HTLV promoter by a transcellular mechanism. HeLa cells containing a CAT reporter gene driven by the HTLV-2 promoter were cocultivated with hematopoietic cells of the B-(Raji), T-(HuT78, Jurkat) and monocyte/promyelocytic (THP-1, U937 and HL60) lineages. Cocultivation with U937 and HuT78 cells constitutively and significantly transactivated the HTLV-2 promoter, while no effect was observed with the other lines. However, activation of other T-cell lines (CEM, Jurkat, Molt-3 and MT-4) with a combination of phorbolester and phytohemagglutinin also resulted in potent transactivation. Supernatant from HuT78 cells exhibited detectable transactivating activity, suggesting that the activation is mediated by a secreted factor(s). This factor also transactivates the HTLV-1 promoter. We used a panel of HTLV-1 LTR deletion mutants to map the responsive elements to this factor(s). Unlike the response element to the HTLV transactivator protein, Tax, which can be mapped to a small region in the enhancer, maximal transactivation by the cellular factor(s) required the complete U3 sequence. Transcellular activation of the HTLV promoter by activated T-cells may play a role in the development of leukemia in HTLV infected individuals.
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PMID:Transcellular activation of the HTLV promoter by human hematopoietic cells. 830 96

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) trans activates the 21-bp enhancer of HTLV-1. A sequence of more than two copies of the 21-bp enhancer is efficiently activated by Tax, but one copy is not activated extensively. Another sequence (TRE-2, positions -163 to -117) adjacent to the 21-bp enhancer in the long terminal repeat of HTLV-1 can enhance a single copy of the 21-bp enhancer activity in trans activation by Tax. This sequence contains motifs related to the Ets- and NF-kappa B-binding sequences, but mutations at these sites indicated that neither is responsive to cooperation with the 21-bp enhancer. A deletion mutation of TRE-2 identified 25 bases at positions -158 to -134 (TRE-2S) as an essential sequence, and TRE-2S was sufficient to give maximum cooperation with one copy of the 21-bp enhancer in trans activation by Tax protein. Using TRE-2S as a probe, we screened a cDNA library of HUT102 cells by the Southwestern (DNA-protein) procedure and isolated two cDNA clones, THP-1 and -2. These two clones encode TRE-2S-binding proteins, and they differ by only an extra 17 amino acids in THP-2. Both THP proteins contain five zinc finger motifs which are strikingly similar to those of the GLI family, an amplified gene product in glyoma cells. The binding site of THP-1 and -2 was GAACCACCCA in TRE-2S, which is highly homologous to the GLI-binding site. These results suggest that binding of THP to TRE-2S may be involved in cooperation with one copy of the 21-bp enhancer in responding to Tax trans activation.
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PMID:A new regulatory element that augments the Tax-dependent enhancer of human T-cell leukemia virus type 1 and cloning of cDNAs encoding its binding proteins. 835 Apr 1

The leukotriene (LT) B4 receptor has been characterized in the human monocyte leukemia THP-1 cell line. Scatchard analysis of [3H]LTB4 specific binding to THP-1 cell membranes revealed a single population of high affinity (KD = 56 pM) and saturable (2000 receptors/cell) binding sites. [3H]LTB4 specific binding was enhanced by divalent cations, but inhibited by both monovalent cations and a non-hydrolysable GTP analogue. Treatment with GTP analogue resulted in a concentration-dependent reduction in the number of high affinity binding sites, accompanied by the appearance of an equal number of binding sites of lower affinity (KD = 1250 pM). In contrast, Scatchard analysis with human polymorphonuclear leukocyte (PMN) membranes consistently revealed two populations of LTB4 receptors (KD = 48 pM and 270 pM). Treatment with GTP analogue, however, converted all these detectable binding sites to the lower affinity state. These data suggest that the LTB4 receptor in both THP-1 cell and PMN membranes exists in interconverting affinity states modulated by G-protein coupling. The similarity between the LTB4 receptors present in these two cell types was also substantiated by target-size analysis by radiation inactivation, which estimated a comparable molecular mass of 56.5 kDa and 52.8 kDa for the THP-1 cell and PMN LTB4 receptors, respectively. Finally, the presence of a single LTB4 receptor in PMN was demonstrated by direct photolabelling. Irradiation of frozen [3H]LTB4 equilibrium binding assay incubations resulted in complete photolysis of [3H]LTB4. Subsequent resolution of the tritiated PMN proteins by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis (PAGE) revealed one major radioactive peak migrating with an apparent molecular weight of 61,000. This peak was identified as the LTB4 receptor since radiolabelling could be completely inhibited by the presence of excess unlabelled LTB4 or the LTB4-receptor antagonist, L-662,328. Photolabelling was also partially inhibited by pretreatment with GTP analogue, consistent with G-protein uncoupling reagents reducing receptor affinity without complete inhibition. In summary, the LTB4 receptor identified in human myeloid cells is a G-protein coupled receptor with interconvertible high and low affinity states, having a molecular mass of 53-61 kDa.
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PMID:Photoaffinity labelling and radiation inactivation of the leukotriene B4 receptor in human myeloid cells. 838 43

Anti-leishmanial activity of chloroform and methanol extracts of Vernonia amygdalina, a plant widely used in Ethiopia for the treatment of parasitic infections, has been assessed in vitro on Leishmania aethiopica. Amastigotes were more sensitive to V. amygdalina than promastigotes. The chloroform extract had a stronger parasiticidal activity, with median effective doses (ED50) of 18.5 micrograms/ml and 13.3 micrograms/ml for promastigotes and amastigotes, than the methanol extract with ED50 of 74.4 micrograms/ml and 45.8 micrograms/ml respectively. Cytotoxicity caused by V. amygdalina to host cells, the human leukaemia monocyte THP-1 cell line, as determined by the methyl tetrazolium assay, resulted in a median lethal dose (LD50) of 19.6 micrograms/ml for the chloroform extract and 243.4 micrograms/ml for the methanol extract. In comparison, the ED50 and LD50 of pentamidine, a standard anti-leishmanial drug, were 0.5 micrograms/ml and 1.4 micrograms/ml respectively. These results indicate that V. amygdalina displays potent anti-leishmanial activities and warrants further investigation.
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PMID:The in vitro activity of Vernonia amygdalina on Leishmania aethiopica. 840 83


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