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

gamma RF-1 is a recently identified transcription factor induced by interferon-gamma (IFN-gamma) which binds to a unique palindromic enhancer, gamma RE-1, in the promoter of the mig gene. This paper describes the ligand-dependent and ligand-independent activation of gamma RF-1 in a cell-free system. gamma RF-1 activity was induced by IFN-gamma in a time-dependent manner from 5 to 60 min in lysates prepared from the human monocytic leukaemia line THP-1 and the human epidermoid carcinoma line A431. The activation of gamma RF-1 in vitro required both ATP and an inhibitor of tyrosine phosphatases (sodium orthovanadate or pervanadate). In the presence of limiting concentrations (micromolar) of ATP, activation was also dependent upon stimulation with IFN-gamma, whereas at millimolar concentrations of ATP, gamma RF-1 was activated by either sodium orthovanadate or pervanadate in the absence of ligand. Based on cell fractionation studies, both membrane and cytosol components were essential for activation of gamma RF-1 in vitro. Consistent with a role for one or more tyrosine kinases in the activation of gamma RF-1, its DNA binding activity was blocked by monoclonal anti-phosphotyrosine antibodies and by the tyrosine kinase inhibitors genistein, lavendustin A and herbimycin A. A comparison with recently described pathways of IFN-mediated transcription factor regulation indicates that the in vitro activation of gamma RF-1 is unique, requiring both membrane and cytosol fractions and inhibition of endogenous tyrosine phosphatase activity.
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PMID:Ligand-dependent and -independent activation of the transcription factor gamma RF-1 in a cell-free system. 754 74

Drug-initiated apoptosis of human leukemia HL-60, THP-1, and U-937 cells was studied via multiparameter flow cytometry and cell sorting. A new flow cytometric method that allows both identification and quantitation of apoptotic cells and estimation of their cell cycle specificity is presented. The method is based on paraformaldehyde fixation followed by staining of F-actin and DNA with fluorescein isothiocyanate (FITC)-phalloidin and propidium iodide (PI), respectively. Bivariate green fluorescence (F-actin) vs. side scatterplots of HL-60 cells treated with 10 microM etoposide for 4 h showed two cell populations, one with high green fluorescence and low side scatter and one with low green fluorescence and high side scatter. Sorting revealed cells with intact nuclei in the high green fluorescence/low side scatter population and cells with fragmented nuclei in the low green fluorescence/high side scatter population, demonstrating that the cells in the latter population were apoptotic. Exposure of HL-60 cells to 10 microM etoposide for 4 h resulted in S-phase selective apoptosis, whereas 5 micrograms/ml cycloheximide initiated apoptosis mainly in G0/G1-phase and S-phase cells. The apoptotic response of HL-60 cells to 20 GY gamma-irradiation was selective for S-phase and G2 + M-phase cells. The present method offers the opportunity to estimate the cell cycle distributions of both the apoptotic and the nonapoptotic cell populations, which is especially valuable when apoptosis occurs in association with cell cycle perturbations. A similar shift from one to two cell populations in green fluorescence vs. side scatter-plots, similar to that observed for HL-60 cells, was observed in the THP-1 and U-937 cell lines secondary to etoposide treatment.
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PMID:A new flow cytometric method for discrimination of apoptotic cells and detection of their cell cycle specificity through staining of F-actin and DNA. 754 98

Aromatase cytochrome P450 mRNA and activity was strongly expressed in THP 1 myeloid leukaemia cells after treatment with phorbol-myristate-acetate (PMA) and dexamethasone, low level expression was caused by calcitriol. mRNA species of 4.0, 3.0, 2.4 and 1.1 kb size were differentially stimulated. After calcitriol-mediated differentiation (72 h, measured by CD 14 expression) mRNA expression was further enhanced by PMA (45-fold), dexamethasone (15-fold), oestradiol (3.7-fold), testosterone (2.5-fold) and androstenedione (3.5-fold). Forskolin, cAMP and follicle stimulating hormone had no stimulatory effect. Oestradiol formation from testosterone (oestradiol radioimmunoassay in culture supernatants) increased to > 2000 pg/ml/10(6) cells/24 h after PMA-stimulation, mirrored mRNA expression and was suppressed below 10% of original values in the presence of 4-OH-androstenedione. Exons I.2 and I.4 were expressed in PMA-stimulated cells only, exon I.3 in both PMA- and dexamethasone-stimulated cells. A new splicing variant was expressed after calcitriol-stimulation, which did not hybridize to an exon II-derived oligonucleotide but to an exon III-derived one. Local aromatisation of androgens into oestradiol may be important in the concerted crosstalk of cells of the monocyte/macrophage lineage with their respective tissues in inflammation and bone metabolism.
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PMID:Expression and regulation of aromatase cytochrome P450 in THP 1 human myeloid leukaemia cells. 754 22

We studied tissue transglutaminase (TGase) expression in human myelomonocytic leukemia cells treated by combinations of all-trans retinoic acid (RA) and 1,25 dihydroxyvitamin D3 (VD). We found that in U937 cells, as in HL-60 and THP-1 cells, RA alone caused an early induction of enzyme activity, correlated with increased mRNA expression. VD alone also induced rapid TGase mRNA expression but in this case TGase enzymatic activity was not measurable until 96 h following onset of treatment. Combinations of both agents had no additional effects over those of RA alone on HL-60 cells, THP-1, and U937 cells during the first 48 h. However, following further incubation, U937 cells expressed increased levels of TGase when treated by both agents. By many criteria, including their sensitivity to various inducers of oxidative burst, lipopolysaccharide-induced production of monokines and in the present work, lysozyme secretion and TGase expression, U937 cells exposed to combinations of RA and VD exhibit a behavior different from those of HL-60 and THP-1 cells. They represent a type of leukemia cell amenable by this treatment to a stage close to that of a terminally differentiated macrophage.
Leukemia 1995 Oct
PMID:Differentiation of U937 myelomonocytic cell line by all-trans retinoic acid and 1,25-dihydroxyvitamin D3: synergistic effects on tissue transglutaminase. 756 22

THP-1 myelomonocytic leukemia cells cultured with either macrophage colony-stimulating factor (M-CSF) or interferon-gamma (IFN-gamma) alone produce, at best, only low levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha). However, combinations of the two factors resulted in at least 3- to 20-fold greater amounts of IL-1 beta and TNF-alpha than would have been predicted by additive mechanisms. This enhanced cytokine production was observed when M-CSF and IFN-gamma were added simultaneously or when M-CSF was added 24 h after addition of IFN-gamma to the cells. Similar results were obtained with fresh human peripheral blood cells treated with IFN-gamma + M-CSF. Cycloheximide treatment of the cultures containing M-CSF and IFN-gamma inhibited the production of IL-1 beta and TNF-alpha. Northern blotting studies revealed no effect of IFN-gamma alone on IL-1 beta or TNF-alpha mRNA production. IL-1 beta and TNF-alpha mRNA expression was observed at 2 and 6 h after treatment with M-CSF or IFN-gamma + M-CSF. Higher TNF-alpha mRNA expression was observed at 2 and 6 h after treatment with IFN-gamma + M-CSF, and higher IL-1 beta mRNA expression was observed at 2 h after treatment with IFN-gamma + M-CSF compared with mRNA levels observed for cells cultured only with M-CSF. These results suggest that the augmented cytokine production resulting from treatments with combinations of M-CSF and IFN-gamma occurs due to increased cytokine mRNA and increased cytokine protein synthesis. In addition to up-regulating cytokines, combinations of IFN-gamma and M-CSF resulted in augmented cell surface expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. This was accompanied by morphological and functional changes that included plastic adherence, extensive homotypic aggregation, and a macrophage-like appearance. These phenotypic changes and enhancements in cytokine expression and cell surface molecule expression may be related to activation of monocytic cells to become cytotoxic effectors by M-CSF and IFN-gamma combinations. In vitro cytotoxicity against A-375 melanoma cells was greatest for cultures that contained M-CSF and IFN-gamma in combination.
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PMID:Activation of cytokine production and adhesion molecule expression on THP-1 myelomonocytic cells by macrophage colony-stimulating factor in combination with interferon-gamma. 759 61

The human monocytic leukaemia cell line THP-1 was induced to differentiate to macrophage-like cells by the addition of phorbol myristoyl acetate (PMA). Subsequently, the cells were enriched in cholesterol and these cholesterol laden cells were used to study the capability of reconstituted discoidal complexes (RDCs), consisting of either human apolipoprotein A1 (apo A1) or recombinant human proapolipoprotein A1 (proapo A1) and phosphatidylcholine (PC), to promote cholesterol efflux. RDCs containing apo A1 and proapo A1 were both effective in the mobilization of intracellular cholesterol, whether this was measured by intracellular cholesterol mass or by the appearance of radiolabelled cholesterol in the supernatant. Using the radiolabelling technique, the activity was saturable and followed Michaelis-Menten kinetics. For both types of complexes and for native HDL the maximum rate of cholesterol removed was approximately 0.5 nmol h-1 per 10(6) cells. For RDCs of proapo A1 and apo A1 and for native HDL the Km values were 3.7, 2.9 and 64.8 micrograms ml-1 respectively. A significant in vitro cholesterol efflux could only be achieved with protein-lipid complexes; no significant export was observed with either free proapo A1 or multilamellar PC liposomes without apolipoprotein. Both RDCs were found to be more active in the mobilization of intracellular cholesterol than HDL isolated from human plasma. The combined results demonstrate that synthetic complexes consisting either of apo A1 or proapo A1 and PC are both active in the in vitro reverse transport of cholesterol.
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PMID:In vitro reverse cholesterol transport from THP-1-derived macrophage-like cells with synthetic HDL particles consisting of proapolipoprotein A1 or apolipoprotein A1 and phosphatidylcholine. 762 33

Microspectrofluorometry allows the analysis of fluorescent molecules such as anthracyclines in the nucleus of isolated living cells. Using this technique, we confirmed that the amount of doxorubicin or THP-doxorubicin incorporated into the nucleus was related to the resistant or sensitive character of K562 cells. It was then extended to the study of fresh leukemic cells and kinetic studies were performed allowing the calculation of the retention rate (RR) of anthracycline (THP-doxorubicin) into the cell nucleus. A reproducibility study confirmed the accuracy of the method. Blast cells collected in patients with acute myeloid (n = 22) or lymphoid (n = 8) leukemia, at diagnosis (n = 26), or in relapse (n = 4) have been studied. RR varied from 8 to 98% independently of the type of leukemia or the clinical status. RR did not correlate either with P-glycoprotein or with CD34 expression although this latter result should be confirmed on a higher number of subjects. Among 18 patients presenting with AML at diagnosis, 14 have been treated with intensive chemotherapy including anthracyclines; the only one who had resistant disease had the lowest RR value. In conclusion, the results obtained here show that microspectrofluorometry allows the performance of kinetic studies on fresh leukemic cells in order to quantify chemo-resistance phenomena related to drug transport.
Leukemia 1995 Aug
PMID:In vitro study of THP-doxorubicin retention in human leukemic cells using confocal laser microspectrofluorometry. 764 25

TGF-beta 1 plays a critical role in inflammatory and repair processes due in part to its ability to provide a potent chemotactic stimulus for inflammatory cells such as neutrophils and monocytes and for fibroblasts which initiate the fibrogenic response. In the present study, we have used synthetic oligopeptides representing the amino acid sequence of the 12.1 kDa monomer of human TGF-beta 1 in an effort to identify a chemotactic epitope on the molecule. A seven residue peptide containing residues 368-374, Val Tyr Tyr Val Gly Arg Lys, was demonstrated to be capable of inducing chemotactic migration of human peripheral blood neutrophils, monocytes, monocyte leukemia cell line THP-1, and infant foreskin fibroblasts. Furthermore, larger peptides from the carboxy-terminal portion of TGF-beta 1 that contained residues 368-374 also induced migration of these cell types. None of the peptides representing the complete amino acid of TGF-beta 1 monomer were able to compete with [125I]hrTGF-beta 1 for binding to TGF-beta cell surface receptors or fibroblasts or THP-1 cells. Implications of these observations are discussed.
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PMID:Identification of a chemotactic epitope in human transforming growth factor-beta 1 spanning amino acid residues 368-374. 765 66

The third component of the interleukin (IL) 2 receptor, gamma chain, is essential not only for IL-2- but also for IL-4-, IL-7-, IL-9-, and IL-15-induced proliferation of lymphocytes. To elucidate the mechanisms by which the gamma chain is expressed, we have analyzed the promoter region of the gamma chain gene. The 633-base pair fragment upstream of the initiation codon showed the promoter activity in human hematopoietic cell lines, Jurkat and THP-1, when linked to the luciferase gene. With a series of 5'-deletion mutants, the basal promoter activity was found in a fragment from nucleotide 80 to 58 upstream from the RNA start site, including an Ets binding sequence. Treatment of cells with either 12-O-tetradecanoylphorbol-13-acetate or phytohemagglutinin but not forskolin induced transcription from the gamma chain gene promoter. A viral trans-acting transcriptional activator, Tax, of human T-cell leukemia virus type I elevated expression of the gamma chain gene. In contrast, IL-2 decreased transcription from the IL-2 receptor gamma chain promoter. These results suggest that expression of the gamma chain is regulated at the transcription level by extracellular stimuli and may be implicated in immune response.
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PMID:Functional analysis of the human interleukin 2 receptor gamma chain gene promoter. 770 94

Human TUR leukemia cells were generated as a subclone of U937 monoblastoid leukemia cells. There was no obvious difference in the ultrastructure of both cell lines. Like in U937 cells, the expression of monocyte-specific surface markers such as CD14 was negligible in TUR cells. U937 cells and other human myeloid leukemia cell lines (HL-60, THP-1) can be induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) to differentiate along the monocytic pathway. In contrast, exposure to TPA had no effect on the induction of the differentiation program in TUR cells. Thus, the presence of leukocyte integrins including CD11 and CD18, which are significantly induced during TPA-induced differentiation of HL-60, U937 and THP-1 cells, remained nearly unchanged at low levels in both TUR and TPA-treated TUR cells. Furthermore, while expression of major histocompatibility complex (MHC) class II antigens on U937 and TPA-treated U937 cells is barely detectable, there was a significantly constitutive expression of MHC class II, particularly human lymphocyte antigen (HLA-DR) on the surface of TUR and TPA-treated TUR cells. Exposure of human myeloid leukemia cells to TPA is also associated with growth arrest resulting either in a retrodifferentiation process or in programmed cell death. In contrast, TUR cells continued to proliferate in the presence of TPA although the proliferative capacity was continuously reduced by increasing concentrations of TPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of human TUR leukemia cells: continued cell cycle progression in the presence of phorbol ester is associated with resistance to apoptosis. 772 Jul 32


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