Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three distinct Fc receptors for IgG, Fc gamma RI, Fc gamma RII and Fc gamma RIII are known to be associated with human myeloid cells. Using mAb specific for these receptors, and the hydridoma cells lines that produce these mAb, we have examined the ability of each of these receptors on different myeloid cells and cell lines to mediate killing of tumor and red cell targets. Hybridoma cells (HC) expressing anti-Fc gamma RI, Fc gamma RII or Fc gamma RIII upon their surface were used as model self-directed tumor targets. Chicken erythrocytes (CE) were used as another type of target cell and in this case effector cell cytotoxicity was mediated by heteroantibodies (HA) composed of Fab fragments of anti-Fc gamma R mAb covalently linked to Fab fragments of rabbit anti-CE antibodies. Monocytes, lymphocytes, polymorphonuclear cells (PMNs) and the myeloid cell lines U937, HL-60 and THP-1 were used as effector cells either in their native state or after activation with rIFN-gamma. Direct comparison of cytotoxicity by the same effector cell population against both tumor and erythroid targets has permitted definitive evaluation of the ability of the different Fc gamma R to promote cytolysis under two different conditions. Monocytes were able to utilize Fc gamma RI, Fc gamma RII and Fc gamma RIII in killing both CE and HC targets, and incubation with rIFN-gamma augmented their ability to kill CE, particularly through Fc gamma RI. Fc gamma RII and Fc gamma RIII mediated killing of CE by untreated neutrophils. rIFN-gamma induced PMNs to express Fc gamma RI and to mediate killing of CE through this receptor. Moreover, HC targets were not lyzed by untreated neutrophils, but rIFN-gamma activated neutrophils killed HC bearing surface anti-Fc gamma RI and anti-Fc gamma RII, but not anti-Fc gamma RIII. Myeloid cell lines HL-60 and U937 were unable to perform cytotoxicity without prior culture with rIFN-gamma, following which they killed CE through Fc gamma RI and Fc gamma RII, but were still incapable of HC lysis. THP-1, another myeloid cell line, was cytotoxic to CE through Fc gamma RI and Fc gamma RII without activation. Following rIFN-gamma treatment, cytotoxicity through these two Fc gamma R increased and was also mediated by Fc gamma RIII but these cells were still unable to kill HC.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Immunol 1989 Oct
PMID:The functional properties of Fc gamma RI, II and III on myeloid cells: a comparative study of killing of erythrocytes and tumor cells mediated through the different Fc receptors. 253 42

Transcription of the low-density lipoprotein receptor (LDL-R) gene in the human monocytic leukemic cell line THP-1 and in the human hepatocarcinoma cell line Hep-G2 is regulated by second messengers of the diacylglycerol-protein kinase C (DAG-PKC), inositol 1,4,5-triphosphate-Ca2+, and cyclic AMP pathways. Exogenous phospholipase C (which releases DAG and inositol 1,4,5-triphosphate), PKC activators (phorbol esters and DAG), Ca2+ ionophores, and a cyclic AMP analog all transiently induced accumulation of LDL-R mRNA. The effects of these three signal-transducing pathways were to a large extent additive. Furthermore, PKC stimulation effected an increase in LDL binding, which suggested that the increase in LDL-R mRNA resulted in an increase in functional cell surface receptor activity. These results suggest that uptake of cholesterol by these cells is under control of both intracellular cholesterol levels and external signals.
Mol Cell Biol 1989 Jun
PMID:Involvement of second messengers in regulation of the low-density lipoprotein receptor gene. 254 77

The ret transforming gene was activated by recombination between two unlinked segments of human DNA, most likely during transfection of NIH 3T3 cells. To further define this transforming gene, we isolated and sequenced ret cDNA clones. The nucleotide sequence indicates that the active ret transforming gene encodes a fusion protein with a carboxy-terminal domain which is 40 to 50% homologous to members of the tyrosine kinase gene family. This tyrosine kinase domain is preceded by a hydrophobic sequence characteristic of a transmembrane domain. Transcription of the ret tyrosine kinase sequence was detected in the SK-N-SH neuroblastoma, HL-60 promyelocytic leukemia, and THP-1 monocytic leukemia cell lines, but not in 25 other human tumor cell lines surveyed. The ret tyrosine kinase may thus represent a cell surface receptor which is expressed in a restricted range of human cells.
Mol Cell Biol 1987 Apr
PMID:ret transforming gene encodes a fusion protein homologous to tyrosine kinases. 303 15

We have adapted a human monocytic leukemia cell line [THP-1c12(+)] so that it can proliferate in a completely protein-free chemically defined medium of an equal mixture of Dulbecco's modified Eagle's minimum essential medium and Ham's F12. This cell line was designated as THP-1c12(-). When a sufficient number of THP-1c12(-) cells was seeded in culture, the maximum cell density after 6 days of culture was 1 X 10(6)/ml with a doubling time of 30 hr. Transferrin showed a slight stimulative effect on the growth of THP-1c12(-) cells, but insulin did not. The surface profile of THP-1c12(-) was the same as that of THP-1c12(+), which possessed Mol. Mo5, LeuM3, My9 and Ia-like antigens as well as a large number of Fc receptors. Phagocytic ability with respect to IgG-coated sheep red blood cells was evident in both THP-1c12(+) and THP-1c12(-) cells. A small percentage of THP-1c12(-) cells retained the ability to reduce nitroblue tetrazolium when stimulated with 12-tetradecanoyl-phorbol-13-acetate. Culture supernatant from THP-1c12(-) stimulated the incorporation of 3H-thymidine into its own cells, suggesting an autocrine mechanism by which the growth of THP-1c12(-) cells is induced in a protein-free medium.
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PMID:Adaptation of a human monocytic leukemia cell line (THP-1) in a protein-free chemically defined medium. 355 Nov 91

A novel cultured cell line, P31/Fujioka, of monocytoid nature was established from leukemic cells in the peripheral blood of a seven-year-old boy with acute monoblastic leukemia. The P31/Fujioka cells have abundant cytoplasm, an indented nucleus of monocytoid appearance, pseudopods detectable by electron microscopy and alpha-naphthyl butyrate esterase activity which is completely inhibited by NaF, but they have no peroxidase activity. Immunologically, the P31/Fujioka cells possess Fc gamma-receptor and phagocytic activity towards sensitized erythrocytes (oxEAIgG), and are reactive with various monoclonal antibodies such as OKM1, anti-Mol, FMC10, FMC12 and OKI1. Chromosome analysis revealed the presence of marker chromosome 11q--due to Nos. 7; 11 translocation and No. 9 pericentric inversion. These findings indicate that the P31/Fujioka cells are derived from the patient's monoblastic leukemia cells and show a more distinct monocyte antigen than other known monocytoid cultured cell lines, U-937 and THP-1. The absence of Epstein-Barr virus nuclear antigen of this line was confirmed.
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PMID:A novel monocytoid cultured cell line, P31/Fujioka, derived from acute monoblastic leukemia. 696 83

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.
Mol Cell Endocrinol 1995 Apr 28
PMID:Expression and regulation of aromatase cytochrome P450 in THP 1 human myeloid leukaemia cells. 754 22

Glutathione (GSH) depletion in mitogen-stimulated T lymphocytes has been shown to markedly inhibit their proliferative response. This block in proliferation is associated with a significant reduction in total RNA and DNA synthesis; however, the specific mechanism involved in this inhibition of proliferation is unknown. Miller et al. have reported that lowering intracellular GSH levels by greater than 30%, in murine and human tumor cell lines of non-hematopoietic origin, leads to down-regulation of HA-, Ki- and N-ras oncogene expression [Miller. A.C., Gafner, J., Clark, E.P. and Samid, D. (1993) Mol. Cell Biol., 13, 4416-4422]. The reduction in ras transcript levels correlated with the extent of GSH depletion and was independent of the specific mode of oncogene activation. Since the activity of p21(ras) is thought to be involved in pathways of T cell activation, we set out to determine whether down-regulation of ras expression in T cells could be the mechanism by which T cell proliferation was inhibited in GSH-depleted T lymphocytes. Despite reducing the GSH level of concanavalin A-activated human peripheral blood mononuclear cells by 66%, no effect on ras mRNA expression was observed. Similarly, no reduction of ras transcript levels were detected in a human T cell line (Jurkat) or in a human monocytic cell line (THP-1) depleted of glutathione. Our results demonstrate that the mechanism by which GSH depletion inhibits T cell proliferation does not appear to involve a decrease in ras mRNA expression. In addition, our results suggest that differences in the regulation of ras mRNA expression may exist between lymphoid/monocytic cells of non-hematopoietic origin.
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PMID:N-ras mRNA expression is unaffected in glutathione-depleted cells of hematopoietic origin. 765 16

The cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) are released by mononuclear phagocytes in vitro after stimulation with mycobacteria and are considered to mediate pathophysiologic events, including granuloma formation and systemic symptoms. We demonstrated that the Mycobacterium tuberculosis cell wall component lipoarabinomannan (LAM) is a very potent inducer of IL-1 beta gene expression in human monocytes and investigated the mechanism of this effect. We localized the LAM-, lipopolysaccharide (LPS)-, and TNF-alpha-inducible promoter activity to a -131/+15 (positions -131 to +15) DNA fragment of the IL-1 beta gene by deletion analysis and chloramphenicol acetyltransferase assay. Within this DNA fragment, there were two novel 9-bp motifs (-90/-82 and -40/-32) with high homology to the nuclear factor-IL6 (NF-IL6) binding site. Site-directed mutagenesis demonstrated that the two NF-IL-6 motifs could be independently activated by LAM, LPS, or TNF-alpha and that they acted in an orientation-independent manner. DNA mobility shift assay revealed specific binding of nuclear protein(s) from LAM-, LPS-, or TNF-alpha-stimulated THP-1 cells to the NF-IL6 motifs. We conclude that the two NF-IL6 sites mediate induction of IL-1 beta in response to the stimuli LAM, LPS, and TNF-alpha.
Mol Cell Biol 1993 Jun
PMID:Regulation of the interleukin-1 beta (IL-1 beta) gene by mycobacterial components and lipopolysaccharide is mediated by two nuclear factor-IL6 motifs. 768 3

Influenza B virus has been aetiologically linked to Reye Syndrome (RS), but the mechanism(s) by which this pathogen could disrupt liver metabolism and produce the hepatic mitochondrial injury characteristic of the syndrome are unknown. In this study, two mechanisms by which infection of hepatocytes with influenza B virus could disrupt cellular metabolism were investigated. (1) virus-induced increase in pro-oxidant iron with subsequent iron-induced lipid peroxidation (LP) and (2) increased membrane permeability. Hep G2 cells, a well-differentiated continuous human liver cell line derived from a hepatoblastoma, were infected with allantoic-fluid derived influenza B Lee/40 virus (AFDV) at a multiplicity of infection of 10 for 24 h; productive infection was confirmed by both haemagglutination of chick erythrocytes and by plaque assay. Infection of Hep G2 cells preloaded with 59Fe-transferrin resulted in increased release of 59Fe (153 +/- 17% of controls, P < 0.03). However, the iron released did not result in increased LP (assessed by thiobarituric acid reactive substances; TBARS). To confirm that this lack of of increase in TBARS was not due to insensitivity of the cell line to pro-oxidant iron, cells were exposed to 15 microM iron ascorbate for 60 min. Production of TBARS was increased (122 +/- 4% of controls, P < 0.0003). Release of 51Cr from infected cells was also increased (128 +/- 12% of controls, P < 0.05); thus the infected cells exhibited a generalized increase in membrane permeability. However, infection did not depress mitochondrial respiration (as assessed by the formation of MTT-f3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide-formazan. To determine if the combination of viral infection and soluble products of activated macrophages would affect mitochondrial respiration, infected hepatocytes were exposed to the supernatant fluid from THP-1 cells which had previously been incubated with lipopolysaccharide at 100 ng ml-1 for 18 h. This supernate did depress the formation of MTT-f (81 +/- 5% of controls, P < 0.03). We conclude that influenza B virus does productively infect Hep G2 cells, and does increase hepatocyte membrane permeability. This effect does not impair mitochondrial respiration directly. However, infection does act in concert with soluble products of activated macrophages to depress hepatic mitochondrial respiration. Whether this interaction can be explained by virus-induced permeability changes and/or other effects of infection deserves further investigation.
Mol Cell Probes 1994 Oct
PMID:Activated THP-1 cells depress mitochondrial respiration in Hep G2 cells infected with influenza B virus. 787 29

Cell extracts from a variety of cell lines, myeloid, T, B, mastocytoma, fibroblast, melanoma and breast carcinoma of human, mouse and guinea pig promoted the growth of a wide variety of cell types, namely human myeloid cells HL-60, human B cells Daudi, human melanoma cells A375-C6, mouse transformed-fibroblast cells L929, human myelomonocytic cells THP-1. Among them, the activities in extracts from U937, A375-C6 and Daudi were characterized because these extracts exhibited much more potent activity. These growth promoting activities were acid-labile, sensitive to 2-mercaptoethanol and to heat treatment at 50C or 70C for 5 min. The activities were also sensitive to proteases indicating the proteinous nature of these active entities. The molecular weight of activities from A375 and Daudi cells were estimated to be 100,000-150,000 daltons by gel filtration high performance liquid chromatography, while that from U937 cells was 60,000-70,000 daltons. The isoelectric point of these activities were 5.5-6.5.
Biochem Mol Biol Int 1994 Apr
PMID:Novel growth promoting activity with a wide target cell spectrum is present in extracts of various cell types. 806 46


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