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

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

Cardiotrophin-1 (CT-1) is a recently discovered cytokine that was isolated based on its ability to induce cardiac myocyte hypertrophy in vitro. In this study, the effects of chronic administration of CT-1 to mice (0.5 or 2 microg by intraperitoneal injection, twice a day for 14 days) were determined. A dose-dependent increase in both the heart weight and ventricular weight to body ratios was observed in the treated groups. The body weights of the animals were unaffected. These results indicate that CT-1 can induce cardiac hypertrophy in vivo. CT-1 was not specific for the heart, however. It stimulated the growth of the liver, kidney, and spleen, and caused atrophy of the thymus. CT-1 administration also increased the platelet counts by 70%, with no change in mean platelet volume. Red blood cell counts were increased in the treated animals, and there was a concomitant increase in haemoglobin concentration. Thus, CT-1 has a broad spectrum of biological activities in vivo. This observation is consistent with previous in-vitro findings showing that the mRNA for CT-1 is expressed in several tissues, and that CT-1 can function through binding to the leukaemia inhibitory factor (LIF) receptor and signalling through the gp130 pathway.
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PMID:In vivo effects of cardiotrophin-1. 905 Jul 50

Oncostatin M (OSM) mediates its bioactivities through two different heterodimer receptors. They both involve the gp130-transducing receptor, which dimerizes with either leukemia inhibitory receptor beta or with OSM receptor beta (OSMRbeta) to generate, respectively, type I and type II OSM receptors. Co-precipitation of gp130-associated proteins, flow cytometry, polymerase chain reaction, and tyrosine phosphorylation analyses allowed the characterization of both types of OSM receptors expressed on the surface of different cell lines. It also allowed the detection of a large size protein, p250, that specifically associates to the type II OSM receptor components and that is tyrosine-phosphorylated after the activation peak of the gp130.OSMRbeta heterocomplex. The restricted expression of type I OSM receptor by the JAR choriocarcinoma cell line, and type II receptor by the A375 melanoma cell line, permitted the characterization of their signaling machineries. Both type I and type II OSM receptors activated Jak1, Jak2, and Tyk2 receptor-associated tyrosine kinases. The information is next relayed to the nucleus by the STAT3 transcriptional activator, which is recruited by both types of OSM receptors. In addition, STAT5b was specifically activated through the gp130.OSMRbeta type II heterocomplex. The signaling pathway differences observed between the common type I LIF/OSM receptor and the specific type II OSM receptor might explain some of the bioactivities specifically displayed by OSM.
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PMID:Signaling of type II oncostatin M receptor. 918 71

The signalling pathway that comprises JAK kinases and STAT proteins (for signal transducer and activator of transcription) is important for relaying signals from various cytokines outside the cell to the inside. The feedback mechanism responsible for switching off the cytokine signal has not been elucidated. We now report the cloning and characterization of an inhibitor of STAT activation which we name SSI-1 (for STAT-induced STAT inhibitor-1). We found that SSI-1 messenger RNA was induced by the cytokines interleukins 4 and 6 (IL-4, IL-6), leukaemia-inhibitory factor (LIF), and granulocyte colony-stimulating factor (G-CSF). Stimulation by IL-6 or LIF of murine myeloid leukaemia cells (M1 cells) induced SSI-1 mRNA expression which was blocked by transfection of a dominant-negative mutant of Stat3, indicating that the SSI-1 gene is a target of Stat3. Forced overexpression of SSI-1 complementary DNA interfered with IL-6- and LIF-mediated apoptosis and macrophage differentiation of M1 cells, as well as IL-6 induced tyrosine-phosphorylation of a receptor glycoprotein component, gp130, and of Stat3. When SSI-1 is overexpressed in COS7 cells, it can associate with the kinases Jak2 and Tyk2. These findings indicate that SSI-1 is responsible for negative-feedback regulation of the JAK-STAT pathway induced by cytokine stimulation.
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PMID:Structure and function of a new STAT-induced STAT inhibitor. 920 27

Oncostatin M (OSM) is a member of the interleukin-6/leukemia inhibitory factor (LIF) family cytokines. While human OSM (hOSM) has been characterized, the murine counterpart had not been isolated. We cloned a murine OSM (mOSM) cDNA as a gene that is induced in hematopoietic cells by a subset of cytokines including IL-3, GM-CSF and Epo. Identity of mOSM was based on overall homology to hOSM and chromosomal gene localization. Human OSM is known to exhibit biological activities similar to LIF, because they share the same functional receptor composed of the LIF receptor and gp130. As compared to hOSM, however, a 1000-fold higher concentrations of mOSM was required to stimulate proliferation of LIF-dependent murine DA1a cells, differentiation of M1 macrophage cells, and inhibition of ES cell differentiation. On the other hand, mOSM inhibited growth of NIH3T3 cells at a 1000-fold lower concentration than that of hOSM. These results indicate that mOSM functions through a receptor which is distinct from that of the LIF receptor. Studies on the physiological role of OSM is underway.
Leukemia 1997 Apr
PMID:Cloning and biological activity of murine oncostatin M. 920 21

Blastodermal cells isolated from newly laid, unincubated eggs are virtually uncommitted cells that exhibit many of the properties of pluripotential stem cells. They can be transferred from donor to recipient embryos and contribute to both somatic tissues and the germline. Blastodermal cells that have been maintained in culture for 7 d express the epitopes ECMA-7 and SSEA-1, which are also expressed by mouse embryonic stem cells. After culture for up to at least 7 d, blastodermal cells retain the ability to differentiate into somatic tissues and the germline both in vivo and in vitro. Proliferation in the absence of differentiation of blastodermal cells is stimulated by the presence of Leukemia Inhibitory Factor (LIF) and other ligands that interact with the gp130 receptor, and differentiation is stimulated by exposure to retinoic acid. Blastodermal cells also possess high levels of telomerase activity, which is shared by immortalized cells and cells within the germline. Blastodermal cells can be transfected and will express foreign genes both in vivo and in vitro. Transfected cells can be isolated by fluorescence activated cell sorting and can be cryopreserved without losing their ability to contribute to either somatic tissues or the germline. These properties of blastodermal cells make them ideal vectors for introducing genetic modifications to the germline.
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PMID:Manipulation of blastodermal cells. 925 Nov 32

Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that is known to require at least two distinct receptor components (LIF receptor alpha-chain and gp130) in order to form a high-affinity, functional, receptor complex. Human LIF binds with unusually high affinity to a naturally occurring mouse soluble LIF receptor alpha-chain, and this property was used to purify a stable complex of human LIF and mouse LIF receptor alpha-chain from pregnant-mouse serum. Recombinant soluble human gp130 was expressed, with a FLAG(R) epitope (DYKDDDDK) at the N-terminus, in the methylotropic yeast Pichia pastoris and purified using affinity chromatography. The formation of a trimeric complex in solution was established by native gel electrophoresis, gel-filtration chromatography, sedimentation equilibrium analysis, surface plasmon resonance spectroscopy and chemical cross-linking. The stoichiometry of this solution complex was 1:1:1, in contrast with that of the complex of interleukin-6, the interleukin-6-specific low-affinity receptor subunit and gp130, which is 2:2:2.
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PMID:Evidence for the formation of a heterotrimeric complex of leukaemia inhibitory factor with its receptor subunits in solution. 927 Oct 90

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

Interleukin 6 (IL-6), oncostatin M (OSM) and leukaemia-inhibitory factor (LIF) share a common signal-transducing subunit in each of their receptors and thus mediate an overlapping spectrum of biological activities. Although all of these cytokines stimulate the production of alpha1-proteinase inhibitor (alpha1-PI) in hepatocyte-derived cells, only OSM is able to up-regulate levels of this inhibitor in epithelial cells originating from the lung. In this study we characterized human lung-derived epithelial-like HTB58 cells for their ability to synthesize alpha1-PI after treatment with IL-6, OSM and LIF. The results demonstrate that the resistance of HTB58 cells to the effects of IL-6 and LIF was not because of a lack of their individual functional receptors and suggest that OSM utilizes two different receptors, gp130/LIF receptor and gp130/OSM receptor, in lung-derived epithelial cells.
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PMID:Oncostatin M, leukaemia-inhibitory factor and interleukin 6 trigger different effects on alpha1-proteinase inhibitor synthesis in human lung-derived epithelial cells. 942 17

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


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