Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transforming growth factor-beta 1 (TGF-beta 1) has been implicated in a variety of responses associated with wound healing and inflammation. Thus, TGF-beta 1 enhances production of several extracellular matrix proteins both in vitro and in vivo, is chemotactic for monocytes, and alters the functioning of lymphocytes. We have examined the ability of TGF-beta 1 to affect the behavior of human THP-1 promonocytic leukemia cells, a cell line with the capacity to differentiate into macrophage-like cells. TGF-beta 1 reduces the growth rate of these cells, induces morphologic changes, and promotes adherence to culture surfaces. In addition, the adherent cell population expresses high levels of esterase activity, acquires the ability to ingest latex beads, and releases elevated levels of interleukin 1. TGF-beta 1-treated cells also express elevated levels of the beta 2 family of integrins. Taken together, these results suggest that TGF-beta 1 is capable of promoting the maturation of promonocytic cells into macrophages. This outcome has implications at wound sites where TGF-beta 1 and a myriad of other factors interact with many cell types to facilitate healing.
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PMID:TGF-beta inhibits proliferation of and promotes differentiation of human promonocytic leukemia cells. 152 33

Pharmacologic differentiation of the promyelocytic leukemia HL60 is associated with an increase in cellular tyrosine phosphatase activity. We asked (a) if this increase might, at least in part, be due to changes in a transmembranous protein-tyrosine phosphatase, CD45; and (b) if CD45 changes similarly in other differentiating leukemias. Differentiation of HL60, several chronic myelogenous leukemias, a monocytic leukemia (THP-1), and a monoblastoid leukemia (U-937) could be induced by phorbol ester, 1,25-dihydroxy vitamin D3, dimethyl sulfoxide, or cyclic AMP analogues. This differentiation was associated with a marked increase in (a) total cellular tyrosine phosphatase activity (2-4-fold as measured by the ability to dephosphorylate a tyrosine-phosphorylated peptide); (b) CD45-specific tyrosine phosphatase activity (2-4-fold); (c) CD45 cell surface expression by flow cytometry (2-5-fold); (d) synthesis of both exon B-dependent M(r) 205,000 and exon ABC- M(r) 185,000 CD45 proteins, as revealed by immunoprecipitation with antisera specific for CD45 isoforms. Both isoforms have enhanced electrophoretic mobility when isolated from the differentiated cells. This enhanced mobility did not appear to be due to decreased stoichiometry of CD45 phosphorylation on serine/threonine residues. Interestingly, 12-O-tetradecanoylphorbol-13-acetate transiently reduced CD45 protein-tyrosine phosphatase activity in the chronic myelogenous leukemia cell RWLeu4 without altering the CD45 amount (as measured by cell surface immunofluorescence). Modulation of CD45 tyrosine phosphatase activity (and protein levels) may play a role in differentiation or in maintaining cells in a nonproliferative state or may represent a phenotypic marker of differentiation.
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PMID:Differentiation-induced changes in protein-tyrosine phosphatase activity and commensurate expression of CD45 in human leukemia cell lines. 153 52

Expression of major histocompatibility complex (MHC) class II genes is induced by interferon-gamma (IFN-gamma) in antigen-presenting cells. When human leukaemia THP-1 and PL-21 cells were pretreated with phorbol ester, IFN-gamma-dependent induction of MHC class II gene was markedly enhanced. To elucidate the mechanism of the phenomenon, we examined the effect of cytokines which were secreted from THP-1 cells by the treatment of phorbol ester. Among those cytokines, interleukin-1 beta (IL-1 beta) had a positive effect on IFN-gamma-dependent induction of MHC class II genes. In order to rule out the possibility that different clones of THP-1 cells respond independently to IFN-gamma or phorbol ester, we showed that all independent single clones expressed MHC class II and produced IL-1 beta by IFN-gamma or phorbol ester, respectively.
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PMID:Stimulatory effect of interleukin-1 beta on the interferon-gamma-dependent HLA-DR production. 162 93

1. The effect of n-alcohols (methanol and ethanol) and anesthetics (lidocaine, thiopental, methohexital and thiamylal) on procoagulant activity (PCA) in human peripheral-blood monocytes and non-adherent cultured leukemia promonocytic U937 and THP-1 cells was examined herein. 2. Exposure of whole blood to ethanol showed no effect on PCA in human monocytes. However, ethanol dose-dependently inhibited LPS-induced PCA in isolated human monocytes. 3. In THP-1 cells, ethanol had no significant effect on PCA in either non-challenged or LPS-induced status. However, the induction of PCA by LPS was substantially inhibited when cells were pretreated with 1% ethanol (v/v) for 72 hr. 4. In U937 cells, n-alcohols and anesthetics resulted in dose-dependent depressions in PCA. Importantly, the percent reduction in LPS-induced PCA was much more pronounced than that in non-challenged PCA. 5. These data clearly suggest that n-alcohols and anesthetics readily inhibit the LPS-stimulatory action on monocytic PCA.
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PMID:Inhibition of endotoxin-induced monocytic procoagulant activity by n-alcohols and anesthetics. 168 19

The effects of combinations of interferons (IFNs) and cAMP-inducing agents on the induction of differentiation of human monocytic leukemia U-937 cells were examined. IFN-gamma induced nitro blue tetrazolium (NBT) reducing activity of U-937 cells in a dose-dependent manner, while cAMP-inducing agents such as cholera toxin, prostaglandin E1, forskolin, and isoproterenol only marginally induced NBT reducing activity. However, they all synergistically increased IFN-gamma induction of NBT reducing activity. Cholera toxin was the most potent of the cAMP-inducing agents. Combination effects of IFN-gamma and cholera toxin on other differentiation-associated markers of alpha-naphthyl acetate esterase activity, morphological maturation, Fc receptors, and surface phenotype were also observed. IFN-alpha and -beta, either alone or in combination with cAMP-inducing agents, did not induce NBT reducing activity. IFN-gamma and cholera toxin also synergistically induced differentiation-associated markers in another human monocytic leukemia cell line, THP-1, and a human myeloblastic leukemia cell line, ML-1. These results suggest that cAMP/A-kinase may be an important but insufficient signal for the maturation process of myelogenous leukemia cells.
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PMID:Enhancement of interferon-gamma-induced differentiation of human monoblastic leukemia U-937 cells by cAMP-inducing agents. 170 96

Human granulocyte colony-stimulating factor (G-CSF) receptors on human acute leukemia cells were investigated using human G-CSF iodolabeled by the lactoperoxidase method. Among various human leukemic cell lines, only cells of myelogenous lineage including HL-60, THP-1 and U937 had one type of high-affinity receptor for G-CSF, as shown by Scatchard analysis. Fresh leukemia cells from 19 patients with acute myelogenous leukemia (AML) were then studied. Specific receptors for G-CSF were demonstrated on blast cells in all 19 cases, the mean number of G-CSF receptors per AML cell ranging from 95 to 1436. G-CSF receptors on AML cells appeared to be a single affinity type, although some variations were observed. The mean number of G-CSF receptors on leukemic cells from patients with either FAB M3 or FAB M2 was greater than that of cells from patients with M1 (p less than 0.01, p less than 0.10, respectively). Moreover, the mean number of receptors for G-CSF on CD13- and CD34-positive AML cells was higher than that on CD13-negative and CD34-positive AML cells (p less than 0.01), and the mean number of G-CSF receptors on CD7-positive AML cells was lower than that for CD7-negative AML cells (p less than 0.10). Since the FAB classification and surface phenotypes reflect maturation stages, our findings indicate that the distribution of G-CSF receptors, even on AML cells, may be related to the maturation process.
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PMID:Human granulocyte colony-stimulating factor receptors in acute myelogenous leukemia. 170 27

1. De novo synthesis of phospholipid and its catabolism in human leukemia monocytic THP-1 cells were investigated. 2. Radiolabelled precursors: [methyl-3H]chloride, [1,2-14C]ethanolamine and myo-[2-3H]inositol were readily incorporated into CHCl3-MEOH extractable lipid fraction as a function of time. 3. The radiolabels derived from choline, ethanolamine and inositol were preferentially incorporated into PC, PE and PI fraction, respectively. The data indicate that de novo PL synthesis takes place, and the CDP-choline pathway is operative as a major pathway for PC synthesized in THP-1 cells. 4. Bacterial endotoxin dose-dependently stimulated the incorporation of radiolabelled precursors. Approximately 50% stimulation in PC and PE synthesis was obtained in 20 hr, while the incorporation of [3H]inositol was rapidly stimulated by 170% within 4 hr, and the stimulation declined drastically thereafter. 5. LPS did not alter the radiolabel distribution into PL in any of the three cases. 6. In pulse-chase studies, the cells prelabelled with radioactive PL were exposed to LPS (1 micrograms/ml). The breakdown of PC was enhanced about 30% within the first 2 hr followed by a stimulated PC synthesis observed in the next 4 hr. In contrast, LPS did not induce the hydrolysis of PE and PI. 7. The data indicate that LPS produces a broad spectrum of stimulatory effects on PL synthesis and selectively stimulates the hydrolysis of PC via phospholipase C/D reaction in THP-1 cells.
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PMID:Bacterial lipopolysaccharide stimulates phospholipid synthesis and phosphatidylcholine breakdown in cultured human leukemia monocytic THP-1 cells. 173 98

We have studied the effect of the DNA topoisomerase I inhibitor camptothecin on growth, differentiation, and gene expression in U-937 human promonocytic leukemia cells. At a concentration of 20 nM, camptothecin caused significant DNA strand breakage and decreased the growth activity by accumulating cells preferentially at the G2 phase of the cycle. The growth arrest occurred concomitantly with an increase in cell size. Under those conditions, camptothecin induced differentiation, as demonstrated by (a) the capacity of the cells to generate reactive oxygen species, (b) the increase in the surface expression of the leukocyte integrins CD11b/CD18 and CD11c/CD18, (c) the increase in the cellular content of the intermediate filament protein vimentin, and (d) the decrease in the surface expression of the transferrin receptor. Camptothecin also induced the expression of differentiation markers in other human myeloid cells, namely, the promonocytic THP-1 and the myelomonocytic HL-60 cell lines. Northern blot assays revealed that camptothecin stimulated the expression of CD11b, CD11c, and vimentin at the mRNA level. Moreover, the drug increased the transcription rate of the vimentin gene, as shown by "run-on" transcription assays.
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PMID:Camptothecin induces differentiation and stimulates the expression of differentiation-related genes in U-937 human promonocytic leukemia cells. 173 86

To elucidate the differentiation-associated expression of enzymes catalyzing arachidonic acid metabolism, we measured arachidonate metabolites by reverse-phase high pressure liquid chromatography in monocytoid leukemia (ML-1, THP-1, and U937) and myeloid leukemia (KG-1) cell lines. Undifferentiated ML-1 or THP-1 cells produced trace amounts of eicosanoids via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways. Upon differentiation induced by phorbol ester (phorbol 12-myristate 13-acetate [PMA]), metabolites via the COX pathway were increased by 100-fold in ML-1 and THP-1 cells, while the LOX products remained barely detectable. All the COX metabolites were elevated, but thromboxane A2 (TXA2) formation was threefold higher in ML-1 cells than in THP-1 cells. Similar time-related increases in COX metabolites were observed in THP-1 cells induced to differentiate with retinoic acid. Undifferentiated U937 cells were capable of generating a much higher quantity of COX products than ML-1 or THP-1 cells, but, upon PMA-induced differentiation, COX products were increased by only two-fold to threefold over the undifferentiated cells and the total COX products in differentiated U937 cells were only one-seventh of those produced by differentiated ML-1 or THP-1 cells. KG-1 cells had an entirely different metabolic profile. They produced a large quantity of a metabolite coeluted with prostaglandin D2, and PMA had no effect on inducing changes in arachidonic acid (AA) metabolism. Increased COX metabolite formation in differentiated THP-1 and ML-1 cells was due to an enhanced level of prostaglandin H synthase enzyme mass, as measured by Western blot analysis. The TXA synthase activity was also increased by approximately 100-fold in PMA-induced ML-1 cells and 10-fold in THP-1 cells. These findings indicate that increased expression of prostaglandin H and TXA synthase enzymes is a feature of differentiated monocytoid leukemia cell lines.
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PMID:Differentiation-associated expression of prostaglandin H and thromboxane A synthases in monocytoid leukemia cell lines. 174 85

Electron microscopic observations of THP-1/E (an etoposide-resistant human monocytic leukaemia cell line) showed a remarkable change of mitochondrial structure. Mitochondria were swollen and cristae were relatively intact. There was no difference in the activity of cytochrome oxidase, an enzyme which contains three subunits coded by mitochondrial DNA (mtDNA) between THP-1/E and THP-1 (the parent cell of THP-1/E). No measurable quantitative change of mitochondrial RNA was observed, but the level of mtDNA in THP-1/E was increased by a factor of about 4 compared with that of mtDNA in THP-1. These results suggest that, on acquisition of resistance to etoposide, some factors affect mitochondria, change its morphology and amplify its DNA.
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PMID:Increased levels of mitochondrial DNA in an etoposide-resistant human monocytic leukaemia cell line (THP-1/E). 183 60


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