scholarly journals Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130.

1994 ◽  
Vol 179 (4) ◽  
pp. 1337-1342 ◽  
Author(s):  
X G Zhang ◽  
J J Gu ◽  
Z Y Lu ◽  
K Yasukawa ◽  
G D Yancopoulos ◽  
...  
Keyword(s):  
Cell Lines ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Biological Activities ◽  
Myeloma Cell ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Signal Transducer ◽  
Neurotropic Factor ◽  
Human Myeloma Cell

Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.

scholarly journals Oncostatin M, leukemia inhibitory factor, and interleukin 6 induce the proliferation of human plasmacytoma cells via the common signal transducer, gp130.

1994 ◽  
Vol 179 (4) ◽  
pp. 1343-1347 ◽  
Author(s):  
N Nishimoto ◽  
A Ogata ◽  
Y Shima ◽  
Y Tani ◽  
H Ogawa ◽  
...  
Keyword(s):  
Cell Surface ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Inhibitory Effect ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Signal Transducer ◽  
Late Antigen ◽  
Common Signal

We analyzed the stimulatory effect of oncostatin M (OSM), leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and the inhibitory effect of anti-IL-6 antibody (Ab), anti-IL-6 receptor monoclonal antibody (mAb), and anti-gp130 mAb on the growth of human plasmacytoma cells freshly isolated from a patient with multiple myeloma. The purified cells showed a plasmacytoid morphology and expressed CD38, CD54, and CD56 antigens but no CD3, CD5, CD10, CD19, CD20, or very late antigen 5. IL-6 receptor (IL-6R) and its signal transducer, gp130, were expressed on their cell surface at a low level. Dose-dependent proliferation of the cells in response to OSM, LIF, and IL-6, but not to IL-11, was observed using [3H]TdR incorporation in vitro. Both anti-IL-6 Ab and anti-IL-6R mAb inhibited the growth of the cells in the presence or absence of exogenous IL-6. These cells release IL-6 but not OSM or LIF into the culture supernatant during short-term culture. Therefore, an autocrine growth mechanism mediated by IL-6, but not by OSM or LIF, was confirmed. Furthermore, anti-gp130 mAb completely inhibited the proliferation of the cells induced by OSM, LIF, as well as IL-6. These data indicate that OSM, LIF, and IL-6 can act as growth factors of human plasmacytoma cells through a common signal transducer, gp130, on their cell surface, and also suggest the potential therapeutic application of anti-gp130 mAb, as well as anti-IL-6R mAb against myeloma/plasmacytomas.

scholarly journals The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin m in rheumatoid arthritis

1997 ◽  
Vol 40 (6) ◽  
pp. 1096-1105 ◽  
Author(s):  
Hideyuki Okamoto ◽  
Masahiro Yamamura ◽  
Yoshitaka Morita ◽  
Seishi Harada ◽  
Hirofumi Makino ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Serum Levels ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Interleukin 11

scholarly journals Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6

Blood ◽  
1989 ◽  
Vol 73 (2) ◽  
pp. 517-526 ◽  
Author(s):  
B Klein ◽  
XG Zhang ◽  
M Jourdan ◽  
J Content ◽  
F Houssiau ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Neutralizing Antibodies ◽  
Myeloma Cell ◽  
B Cell Differentiation ◽  
Myeloma Cells ◽  
Autocrine Regulation ◽  
Spontaneous Proliferation ◽  
Human Myeloma Cell

Abstract To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.

Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells

2016 ◽  
Vol 28 (5) ◽  
pp. 608 ◽  
Author(s):  
Wittaya Chaiwangyen ◽  
Stephanie Ospina-Prieto ◽  
Diana M. Morales-Prieto ◽  
Francisco Lazaro Pereira de Sousa ◽  
Jana Pastuschek ◽  
...  
Keyword(s):  
Dna Binding ◽  
Cell Lines ◽  
Binding Capacity ◽  
Binding Activity ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Therapeutic Interventions ◽  
Leukaemia Inhibitory Factor ◽  
Tetrazolium Salt ◽  
Signal Transducer

Leukaemia inhibitory factor (LIF) and oncostatin M (OSM) are pleiotropic cytokines present at the implantation site that are important for the normal development of human pregnancy. These cytokines share the cell membrane receptor subunit gp130, resulting in similar functions. The aim of this study was to compare the response to LIF and OSM in several trophoblast models with particular regard to intracellular mechanisms and invasion. Four trophoblast cell lines with different characteristics were used: HTR-8/SVneo, JEG-3, ACH-3P and AC1-M59 cells. Cells were incubated with LIF, OSM (both at 10 ng mL–1) and the signal transducer and activator of transcription (STAT) 3 inhibitor S3I-201 (200 µM). Expression and phosphorylation of STAT3 (tyr705) and extracellular regulated kinase (ERK) 1/2 (thr202/204) and the STAT3 DNA-binding capacity were analysed by Western blotting and DNA-binding assays, respectively. Cell viability and invasiveness were assessed by the methylthiazole tetrazolium salt (MTS) and Matrigel assays. Enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 was investigated by zymography. OSM and LIF triggered phosphorylation of STAT3 and ERK1/2, followed by a significant increase in STAT3 DNA-binding activity in all tested cell lines. Stimulation with LIF but not OSM significantly enhanced invasion of ACH-3P and JEG-3 cells, but not HTR-8/SVneo or AC1-M59 cells. Similarly, STAT3 inhibition significantly decreased the invasiveness of only ACH-3P and JEG-3 cells concomitant with decreases in secreted MMP-2 and MMP-9. OSM shares with LIF the capacity to activate ERK1/2 and STAT3 pathways in all cell lines tested, but their resulting effects are dependent on cell type. This suggests that LIF and OSM may partially substitute for each other in case of deficiencies or therapeutic interventions.

scholarly journals Infection with human T-lymphotropic viruses leads to constitutive expression of leukemia inhibitory factor and interleukin-6

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1827-1832 ◽  
Author(s):  
RB Lal ◽  
D Rudolph ◽  
C Buckner ◽  
D Pardi ◽  
WC Hooper
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Constitutive Expression ◽  
Cellular Systems ◽  
Inhibitory Factor ◽  
Infected Cell Line ◽  
Proliferating Cells ◽  
Human T Cell

Abstract Leukemia inhibitory factor (LIF), similar to interleukin-6 (IL-6), is a glycoprotein growth factor and differentiation regulator that has pleiotropic activity in several cellular systems. Recent reports of constitutive IL-6 production from spontaneously proliferating cells from human T-cell leukemia virus (HTLV)-infected individuals led us to examine the expression of IL-6 and LIF during HTLV infection. In vitro infection of peripheral blood lymphocytes with HTLV-I was associated with production of both soluble LIF and IL-6 in conjunction with the increasing HTLV antigen concentration. Northern blot analysis of T-cell lines generated from individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II (Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression of LIF and IL-6 transcripts, as compared with uninfected cell lines (HuT-78, Jurkat). The constitutive expression of LIF and IL-6 was independent of presence of IL-2 in the culture medium, as both IL-2-independent (MT-2, HuT-102, SP, Mo-T) and IL-2-dependent (FS, EG, H2A, H2E) cell lines expressed LIF and IL-6 transcripts. Furthermore, LIF and IL-6 RNA expression in an HTLV-I- infected cell line (MT-2) was enhanced by phorbol ester stimulation via mechanisms that appear to be dependent on the posttranscriptional regulatory controls. These results show that both LIF and IL-6 are produced by HTLV-I- and HTLV-II-infected cells, which could potentially alter the transcriptional regulation of HTLV gene expression by inducing certain early response genes.

scholarly journals Oncostatin M, leukaemia-inhibitory factor and interleukin 6 trigger different effects on α1-proteinase inhibitor synthesis in human lung-derived epithelial cells

1998 ◽  
Vol 329 (2) ◽  
pp. 335-339 ◽  
Author(s):  
Joanna CICHY ◽  
Stefan ROSE-JOHN ◽  
James TRAVIS
Keyword(s):  
Epithelial Cells ◽  
Interleukin 6 ◽  
Proteinase Inhibitor ◽  
Human Lung ◽  
Biological Activities ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Common Signal

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 α1-proteinase inhibitor (α1-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 α1-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.

Different epitopes are required for gp130 activation by interleukin-6, oncostatin M and leukemia inhibitory factor

FEBS Letters ◽  
2000 ◽  
Vol 468 (2-3) ◽  
pp. 120-124 ◽  
Author(s):  
Andreas Timmermann ◽  
Stefan Pflanz ◽  
Joachim Grötzinger ◽  
Andrea Küster ◽  
Ingo Kurth ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Oncostatin M ◽  
Inhibitory Factor

scholarly journals Differential regulation of macrophage differentiation in response to leukemia inhibitory factor/oncostatin-M/interleukin-6: the effect of enforced expression of the SCL transcription factor

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 379-390 ◽  
Author(s):  
T Tanigawa ◽  
N Nicola ◽  
GA McArthur ◽  
A Strasser ◽  
CG Begley
Keyword(s):  
Growth Factors ◽  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Differential Regulation ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Macrophage Phenotype ◽  
Colony Stimulating Factor ◽  
Macrophage Differentiation ◽  
Stimulating Factor

The physiologic program of macrophage differentiation normally proceeds in a coordinated manner in response to several different growth factors. Although the utilization of common receptor subunits may explain in part overlapping biologic functions, mechanisms by which unique actions are mediated remain obscure. We examined growth factor- induced macrophage differentiation in M1 leukemia cells that simultaneously display receptors for interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and Oncostatin-M (OSM). Differentiation induced by all three factors was associated with decreased expression of transcription factors myb and SCL, increased expression of macrophage markers, and suppression of proliferation. Cell lines were established in which SCL expression was enforced. In the absence of growth factors, cells were indistinguishable from parental cells. However, LIF (or OSM)- induced macrophage differentiation was perturbed; there was failure to undergo morphologic differentiation, disturbed expression of lysozyme and Mac1 alpha, and failure to suppress proliferation. Surprisingly the perturbation of macrophage differentiation did not apply to induced expression of macrophage colony-stimulating factor (M-CSF) or granulocyte colony stimulating factor (G-CSF) receptors. This dissociation of elements normally coordinated in a macrophage differentiation program applied at a clonal level. There was no disturbance of IL-6-induced macrophage differentiation. These data directly implicate SCL in components of the macrophage differentiation program (suggesting that LIF receptor/gp130 heterodimers utilize an SCL- inhibitable pathway while gp130 homodimers do not) and demonstrate differential-regulation of components of the mature macrophage phenotype.

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