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)

P48 is a 48 kDa monocytic differentiation/activation factor previously purified from the conditioned medium of the Reh human pre-B cell leukaemia cell line. It induces growth arrest and differentiation of HL-60 human promyelocytic leukaemia cells along the monocytic pathway and the production of the cytokines interleukin 1, tumour necrosis factor-alpha and interleukin 6 in human monocytes and monocytic cell lines. The cDNA for P48 was cloned from Reh cellular RNA using 3' reverse amplification of cDNA ends. Southern blot probing with P48 cDNA revealed hybridization with DNA from Reh and Molt-4 cells, but not with DNA from human peripheral blood mononuclear cells. Subsequent studies using PCR and Southern analysis revealed P48 sequences in DNA isolated from Mycoplasma fermentans but not M. hominis, M.iowae, M.synoviae or M.lypophilum. Although initial studies using Mycoplasma culture and hybridization techniques had failed to reveal Mycoplasma infection in our Reh and Molt-4 cell lines, subsequent PCR studies using Mycoplasma genus-specific rRNA primrs revealed Mycoplasma sequences in these cell lines. Using the P48 cDNA probe, we isolated a genomic clone from M. fermentans DNA which was found to be 98.5% identical with the P48 cDNA clone, and the deduced amino acid sequence agreed with N-terminal microsequencing data for P48 protein purified from the Reh cell line conditioned medium. The 5' end of the gene has a number of consensus sequences characteristic of prokaryotic genes, and the deduced amino acid sequence has a number of features suggesting that P48 is a lipoprotein. The P48 cDNA was expressed in pMAL in Escherichia coli, and the 60 kDa expressed fusion protein was found to react with anti-P48 antibodies on Western blots. This is consistent with a pMAL fusion protein representing the sum of the 42 kDa maltose-binding protein and 18 kDa of P48 recombinant protein, suggesting that native P48 has significant post-translational modification. Consistent with this, Northern blot studies revealed a single 1 kb transcript. The recombinant fusion protein was found to possess anti-proliferative activity against HL-60 cells, and antibodies against recombinant P48 were found to block the biological activity of native P48 isolated from conditioned medium. These studies demonstrate that P48, a molecule with immunomodulatory and haematopoietic differentiation activities, is derived from M. fermentans or a closely related species. P48 may be important in the pathophysiology of Mycoplasma infections and may be useful in dissecting the mechanisms involved in mammalian haematopoietic cell differentiation, immune function and cytokine biosynthesis.
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PMID:cDNA and genomic cloning and expression of the P48 monocytic differentiation/activation factor, a Mycoplasma fermentans gene product. 892 Oct

Three cytokines, interleukin 6 (IL-6), leukaemia inhibitory factor (LIF), and oncostatin M (OSM), that bind to composite receptors including a common signal transducer gp130 suppressed proliferation of a mouse B-cell hybridoma cell line 2E3-O cultured in serum-free medium, while they enhanced antibody production of the cells. The specific growth rate of the cells reduced from 1.0/day for control to 0.6/day for the cultures supplemented with IL-6, LIF, or OSM at 1, 4, or 2 ng/ml, respectively. The antibody productivity increased five-fold when the cells were cultured with IL-6, LIF, or OSM at 1, 25, or 20 ng/ml, respectively. Transforming growth factor beta1(TGF-beta1) similarly suppressed growth of the cells at the concentration of 5 ng/ml, while it did not enhance the antibody production. Cell cycle analysis revealed that IL-6 induced the cells to be arrested at G1 phase of the cell cycle more intensively than TGF-beta1, indicating that IL-6 and TGF-beta1 suppressed the growth through mutually different mechanisms. As a whole, this work suggests that gp130, which is commonly involved in each receptor for IL-6, LIF, and OSM, transduces signals for suppressing proliferation and possibly for enhancing antibody production in the hybridoma cells.
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PMID:Cytokines involving gp130 in signal transduction suppressed growth of a mouse hybridoma cell line and enhanced its antibody production. 905 Jul 46

The secreted phospholipase A2 (sPLA2) is released from hepatoma cells after stimulation with interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta), and is considered to act as acute phase protein. In the present study, the regulation of sPLA2 secretion by two other members of the IL-6 cytokine family, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), and the corticosteroid dexamethasone were investigated. Only a marginal increase in sPLA2 activity in cell culture supernatants of HepG2 cells was observed upon stimulation for 24 h with LIF, whereas OSM increased the activity about 10-fold and proved to be even more effective than the combination of IL-6 and TNF-alpha, the best known stimuli so far. sPLA2 activity was synergistically enhanced by OSM plus TNF-alpha (15-fold) or IL-1 beta (20-fold). Changes in sPLA2 activity were reflected at mRNA levels. Cytokine induction of sPLA2 mRNA was comparable to the induction of haptoglobin mRNA. The effect of dexamethasone on the expression of both genes, in contrast, was different: cytokine-induced haptoglobin mRNA expression was enhanced, whereas sPLA2 mRNA expression was partially inhibited by dexamethasone resulting in decreased sPLA2 activity. The strong induction by OSM in HepG2 cells thus confirmed sPLA2 as acute phase protein, whereas the effect of dexamethasone was comparable to the one observed in other cell types.
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PMID:Glucocorticoids inhibit oncostatin M-induced phospholipase A2 gene expression in human hepatoma cells. 912 8

We have examined the in situ transcription of leukaemia inhibitory factor (LIF) in brain tissue from 3 cases of subacute sclerosing panencephalitis (SSPE) and in 2 non-neurological control brains. This has been compared with expression of interleukin 2 (IL-2), interleukin 6 (IL-6) and tumour necrosis factor beta (TNF beta) in the same tissues. All of the cytokines in the study were expressed in cells in the inflammatory infiltrate as well as in glial cells. LIF mRNA was also found to be expressed in neurons, in foci where these cells were also virally infected. No hybridization was found with any of the probes in areas of SSPE brain, which were negative for measles virus RNA or in the non-neurological control cases, although expression was demonstrated in the latter by use of reverse transcription-polymerase chain reaction (RT-PCR). Differentiated, cultured human neuronal cells were also positive, by RT-PCR, for LIF. This is the first demonstration of LIF expression in human brain and the results suggest that this cytokine is up-regulated, in several cell types, including neurons, following virus infection.
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PMID:Leukaemia inhibitory factor mRNA is expressed in the brains of patients with subacute sclerosing panencephalitis. 920 69

Cardiotrophin 1 (CT-1) is a recently described cytokine sharing many biological properties with those reported previously for leukaemia inhibitory factor (LIF). In the present study we show that CT-1 binds to the KB epidermoid cancer cell surface through a tripartite receptor complex which includes the gp130 signal transducing protein, LIF receptor beta (LIFR beta) and a third component displaying a molecular weight of 80 kDa. CT-1 activates gp130 and LIFR beta transducing components, as attested by analysing their tyrosine phosphorylation level. The activation process is relayed to the nucleus by the recruitment of the STAT3 transcription factor. Analysis of KB cell line culture supernatants after CT-1 treatment indicates that CT-1 stimulates the production of interleukin 6 (IL-6) in a time- and dose-dependent manner. This stimulation of IL-6 production by CT-1 is associated with an increase in intracellular levels of IL-6 mRNA. This study suggests that at least in some pathological situations CT-1 might represent an immunomodulator regulating cytokine-induced gene products.
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PMID:Regulation of interleukin 6 expression by cardiotrophin 1. 932 15

The purpose of this study was to assess the role of interleukin 6 (IL-6) in feline uveitis by measuring IL-6 activity in the serum and aqueous humor of cats. Serum and aqueous humor was collected from clinically normal, random source cats (n = 10); clinically normal, specific-pathogen free cats experimentally inoculated with Toxoplasma gondii strain ME49 and sampled sequentially for 20 months (n = 4); and client-owned cats with uveitis (n = 27). Interleukin 6 activity was measured in each sample. Client-owned cats with uveitis were also evaluated for evidence of present or prior exposure to T. gondii, feline leukemia virus, feline immunodeficiency virus, and feline coronaviruses. Interleukin 6 activity was non-detectable or low in serum from cats of each group. Interleukin 6 activity was not detected in aqueous humor of clinically normal cats. Interleukin 6 activity was detected in 22/27 (81.5%) aqueous humor samples from cats with uveitis, with a range of 28.9 U ml(-1)-15702.9 U ml(-1) (mean = 1911.9 U ml[-1], SD = 3946.7 U ml[-1]). Serologic evidence of exposure to T gondii, feline immunodeficiency virus, feline leukemia virus, or a coronavirus was present in 21/27 (77.8%) cats with uveitis. Interleukin 6 was detected in the aqueous humor of 18/21 (85.7%) and 3/6 (50%) of the cats with and without serologic evidence of exposure to one to the infectious diseases, respectively. Statistically significant increases in mean IL-6 activity in aqueous humor were found for cats with any evidence of infection with T. gondii, for cats with T. gondii antigen in aqueous humor and for cats with coronavirus antibody titers > or = 1:100. Aqueous humor IL-6 activity was greater than corresponding serum IL-6 activity in 21/27 cats. These results show that IL-6 is produced intraocularly in some cats with uveitis and that IL-6 may be a mediator of uveitis in cats.
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PMID:Elevated interleukin 6 activity in aqueous humor of cats with uveitis. 934 36

Oncostatin M (OSM) is a cytokine produced by activated T lymphocytes and macrophages. OSM is structurally and functionally related to leukaemia inhibitory factor (LIF), another cytokine in the interleukin 6 (IL-6) family. The biological activities of OSM are mediated through two types of receptor complexes, the LIF/OSM shared receptor (type I) and OSM-specific receptor (OSM-R, type II), which is composed of gp130 as a binding subunit and a newly identified affinity conversion subunit, OSM-R beta. Previous research conducted in the authors' laboratory has shown that OSM inhibits the growth of several breast cancer cell lines. To investigate whether OSM has a similar effect in primary normal human mammary epithelial (HME) cells, the activity of OSM in HME cells derived from four donors was examined. OSM produced a dose-dependent inhibition of DNA synethesis in these cells. In order to determine the receptor subtypes mediating OSM activity in HME and breast cancer cells, flow cytometry analysis using anti-gp130mAb and anti-OSM-R beta mAb was performed. In these studies, the authors were able to examine expressions of gp130 and OSM-R beta. In addition, quantitative RT-PCR assays were conducted to measure expressions of the mRNAs of the subunits for type I and type II OSM receptor. The results show that HME cells and most breast cancer cell lines express both the type I and the type II OSM receptors. However, type II, OSM-specific receptors are expressed at a higher levels than type I, OSM/LIF shared receptors. Accordingly, we compared the growth regulatory activities of OSM with LIF in HME cells and in breast cancer cells. In contrast to the inhibitory activity of OSM, LIF stimulated the growth of breast cancer cells, whereas it had no effect on normal mammary epithelial cell growth. Together, these data suggest that OSM plays an inhibitory role in normal and malignant mammary epithelial cell growth in vitro. OSM activity is mediated by the OSM-specific receptor (type II), not by the OSM/LIF shared receptor.
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PMID:Oncostatin M-specific receptor expression and function in regulating cell proliferation of normal and malignant mammary epithelial cells. 961 75

In this study the authors assessed plasma leukaemia inhibitory factor (LIF), interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6R) concentrations in 28 patients undergoing coronary artery bypass graft (CABG) with extracorporeal circulation (ECC). Plasma IL-6 levels increased during ECC, reaching a 33-fold increase 6 h after surgery as compared to pre-operative values. In contrast, plasma sIL-6R and LIF concentrations did not vary significantly during cardiac surgery. Thus, LIF is not implicated in the haematological changes and in the inflammatory syndrome observed after CABG. Despite the fact that LIF and IL-6 exhibit several common biological activities, the production of these two cytokines is differently regulated during cardiac surgery with ECC. Plasma IL-6 levels increased during cardiac surgery while sIL-6R levels did not changed. These data contrast with the decreased sIL-6R concentrations with concomitantly high IL-6 levels in patients with sepsis syndrome suggesting that inflammatory reactions in sepsis and after cardiopulmonary bypass are triggered by different mechanisms.
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PMID:Plasma leukaemia inhibitory factor, interleukin 6 and soluble interleukin 6 receptor levels during cardiopulmonary bypass with extracorporeal circulation. 961 76

Selective death of magnocellular vasopressinergic neurons in the hypothalamus has been reported in cases of hereditary and idiopathic diabetes insipidus and after experimental lesions of the hypothalamo-neurohypophyseal pathway. To identify trophic factors that promote survival of these neurons, an in vitro model system was established in which organotypic cultures of the rat hypothalamic paraventricular nucleus were maintained in chemically-defined medium. We observe that the majority of magnocellular vasopressinergic neurons die in these cultures, while other cell populations such as corticotrophin-releasing factor producing parvicellular and oxytocin producing magnocellular cells retain a well preserved cytoarchitectonic organization. Degenerating vasopressinergic cells exhibit morphological signs of apoptosis and stained positively when analysed by the terminal deoxynucleotidyl transferase biotinylated dUTP nick end-labelling assay. Partial survival of vasopressinergic neurons occurred after co-culturing the paraventricular nucleus with neurohypophyseal explants, indicating that target-derived factors may be required for the survival of these neurons. Cell survival is dramatically increased by the administration of ciliary neurotrophic factor and leukemia inhibiting factor, but not by interleukin 6 or the members of the neurotrophin family. Reverse transcription-polymerase chain reaction followed by Southern analysis shows the presence of ciliary neurotrophic factor messenger RNA in the neurohypophysis. Thus, endogenous ciliary neurotrophic factor and leukemia inhibiting factor, produced by neurohypophyseal cells may function as a physiological survival factor for neurosecretory vasopressinergic neurons.
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PMID:Magnocellular vasopressinergic neurons in explant cultures are rescued from cell death by ciliary neurotrophic factor and leukemia inhibiting factor. 975 24

Human bone marrow stromal cells regulate haematopoiesis by releasing cytokines such as leukaemia inhibitory factor (LIF) and interleukin 6 (IL-6). We have investigated the effects of 5 lipid mediators (i.e. 12-HETE, 15-HETE, platelet-activating factor (PAF), LTB4 and prostaglandin E2 (PGE2)) on their LIF and IL-6 synthesis. 12-HETE, 15-HETE and LTB4 (both at 1 microM) stimulate the LIF production by human bone marrow stromal cells grown in 10% fetal calf serum (FCS). In contrast, PAF and PGE2 have no effect. 12-HETE (1 microM) enhances LIF synthesis in serum free medium 7.7-fold and stimulates IL-1 induced LIF production. 12-HETE, 15-HETE, PAF and LTB4 have no effect on the spontaneous, serum- and cytokine-induced IL-6 synthesis by bone marrow stromal cells. In contrast PGE2 significantly stimulates serum-induced IL-6 synthesis. This study reports for the first time that lipid mediators may act on human haematopoiesis by modulating LIF and IL-6 synthesis by bone marrow stromal cells. Particularly, 12-HETE enhances LIF but not IL-6 synthesis. The different regulation of IL-6 and LIF synthesis in response to lipid mediators highlights the complexity of the cytokine regulation into the human bone marrow.
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PMID:Effects of lipid mediators on the synthesis of leukaemia inhibitory factor and interleukin 6 by human bone marrow stromal cells. 981 31


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