scholarly journals Differential effects of oncostatin M and leukaemia inhibitory factor expression in astrocytoma cells

2001 ◽  
Vol 355 (2) ◽  
pp. 307-314 ◽  
Author(s):  
Aneta KASZA ◽  
Krzysztof ROGOWSKI ◽  
Witold KILARSKI ◽  
Radoslaw SOBOTA ◽  
Tytus BERNAS ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Janus Kinase ◽  
Oncostatin M ◽  
Biologically Active ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Stable Cell Line ◽  
Astrocytoma Cells ◽  
Autocrine Stimulation

The effects of the production of two closely related cytokines, oncostatin M (OSM) and leukaemia inhibitory factor (LIF), by astrocytoma cells were investigated using the stable cell line human U373-MG, which expressed and secreted both biologically active polypeptides. The expression of LIF by these cells caused resistance to this cytokine due to loss of the LIF receptor (LIFR), from the cell surface, suggesting its retention. In contrast, cells expressing OSM were stimulated by this cytokine, utilizing an autocrine mechanism, and possessed receptors for OSM, but not LIF, on the cell surface. In these cells the continuous up-regulation of OSM-induced gene expression was found even though the Janus kinase-signal transducer and activator of transcription (‘JAK/STAT’) pathway was almost exhausted due to long-term autocrine stimulation of the cells by OSM. The amount of LIFR was down-regulated in both LIF- and OSM-producing cells and this effect was not found in wild-type U373-MG cells treated with externally added cytokines. To investigate the mechanism of autocrine stimulation by OSM we constructed a stable cell line expressing a form of OSM that is retained in the endoplasmic reticulum (ER). This biologically active cytokine was not secreted, but was localized in the ER. In addition, it did not stimulate the astrocytoma cells in an autocrine manner. We conclude that expression of LIF causes resistance of astrocytoma cells to this cytokine, whereas expression of OSM leads to autocrine stimulation.

scholarly journals Differential effects of oncostatin M and leukaemia inhibitory factor expression in astrocytoma cells

2001 ◽  
Vol 355 (2) ◽  
pp. 307 ◽  
Author(s):  
Aneta KASZA ◽  
Krzysztof ROGOWSKI ◽  
Witold KILARSKI ◽  
Radoslaw SOBOTA ◽  
Tytus BERNAS ◽  
...  
Keyword(s):  
Oncostatin M ◽  
Inhibitory Factor ◽  
Leukaemia Inhibitory Factor ◽  
Differential Effects ◽  
Astrocytoma Cells ◽  
Factor Expression

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 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.

scholarly journals Autocrine stimulation by erythropoietin (Epo) requires Epo secretion

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2649-2662 ◽  
Author(s):  
JL Villeval ◽  
MT Mitjavila ◽  
I Dusanter-Fourt ◽  
F Wendling ◽  
P Mayeux ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Parental Cell ◽  
Parental Cell Line ◽  
Phenotypic Analysis ◽  
Growth And Survival ◽  
Retention System ◽  
Autocrine Stimulation

Abstract Erythropoietin (Epo) autocrine stimulation has been implicated in erythroblastic leukemia. To examine whether this stimulation could occur intracellularly, we developed Epo autocrine models of stimulation in the human pluripotent UT-7 cell line. Retroviral expression of Epo totally abolished the growth factor requirement of UT-7 cells. Autonomous proliferation was not cell density-dependent and occurred at a unicellular level, showing a genuine autocrine mode of stimulation. Total blockage of Epo secretion induced by the endoplasmic reticulum- retention amino acids Lys-Asp-Glu-Leu (KDEL) signals in 11 lines prevented autonomous proliferation, whereas a leaky retention system, observed in 3 other lines, resulted in limited autocrine stimulation without true long-term autonomous proliferation. Production of Epo, in contrast to KDEL-modified Epo, induced reductions in Epo binding, Epo receptor (EpoR) mRNA, and phosphorylation levels similar to those induced by the addition of exogenous Epo to the parental cell line. In addition, autonomous growth and survival were inhibited by the addition of Epo-neutralizing antibodies, affording evidence that autocrine stimulation through EpoR activation takes place on the cell surface. Finally, phenotypic analysis of the virus-infected clones indicated that Epo production did not change the differentiative capacities of UT- 7 cells. All these data show that Epo autocrine stimulation is dependent on Epo secretion and takes place on the cell surface. From all analyzed parameters, the effects of Epo autocrine stimulation and those of exogenously added Epo appear to be identical.

scholarly journals Autocrine stimulation by erythropoietin (Epo) requires Epo secretion

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2649-2662 ◽  
Author(s):  
JL Villeval ◽  
MT Mitjavila ◽  
I Dusanter-Fourt ◽  
F Wendling ◽  
P Mayeux ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Neutralizing Antibodies ◽  
Parental Cell ◽  
Parental Cell Line ◽  
Phenotypic Analysis ◽  
Growth And Survival ◽  
Retention System ◽  
Autocrine Stimulation

Erythropoietin (Epo) autocrine stimulation has been implicated in erythroblastic leukemia. To examine whether this stimulation could occur intracellularly, we developed Epo autocrine models of stimulation in the human pluripotent UT-7 cell line. Retroviral expression of Epo totally abolished the growth factor requirement of UT-7 cells. Autonomous proliferation was not cell density-dependent and occurred at a unicellular level, showing a genuine autocrine mode of stimulation. Total blockage of Epo secretion induced by the endoplasmic reticulum- retention amino acids Lys-Asp-Glu-Leu (KDEL) signals in 11 lines prevented autonomous proliferation, whereas a leaky retention system, observed in 3 other lines, resulted in limited autocrine stimulation without true long-term autonomous proliferation. Production of Epo, in contrast to KDEL-modified Epo, induced reductions in Epo binding, Epo receptor (EpoR) mRNA, and phosphorylation levels similar to those induced by the addition of exogenous Epo to the parental cell line. In addition, autonomous growth and survival were inhibited by the addition of Epo-neutralizing antibodies, affording evidence that autocrine stimulation through EpoR activation takes place on the cell surface. Finally, phenotypic analysis of the virus-infected clones indicated that Epo production did not change the differentiative capacities of UT- 7 cells. All these data show that Epo autocrine stimulation is dependent on Epo secretion and takes place on the cell surface. From all analyzed parameters, the effects of Epo autocrine stimulation and those of exogenously added Epo appear to be identical.

scholarly journals Erythropoietin-induced tyrosine phosphorylations in a high erythropoietin receptor-expressing lymphoid cell line

Blood ◽  
1992 ◽  
Vol 80 (8) ◽  
pp. 1923-1932 ◽  
Author(s):  
J Damen ◽  
AL Mui ◽  
P Hughes ◽  
K Humphries ◽  
G Krystal
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Tyrosine Phosphorylation ◽  
Erythropoietin Receptor ◽  
Biologically Active ◽  
Erythroid Progenitor ◽  
Retroviral Gene Transfer ◽  
Molecular Weights ◽  
Erythroid Progenitor Cells ◽  
Major Species

Abstract Retroviral gene transfer of the murine erythropoietin receptor (EpR) cDNA into the pro-B-cell line, Ba/F3, was used to generate cells expressing high EpR levels. One of the resulting clones, Ba/F3 clone C5, contained 5 integrated copies of the gene and expressed, at the cell surface, a single affinity class of EpRs at 10 to 15 times the level present on spleen cells from phenylhydrazine-treated mice. Cross- linking studies with clone C5, using 125I-Ep, yielded the same two 105- and 88-Kd major species as that seen with typical erythroid cells. This was distinct from that obtained with EpR-transfected COS cells or L cells, which gave species of 88 and 65 Kd. This suggests that the biologically active EpR complex generated in this Ba/F3 cell line may closely resemble that present in native Ep-responsive erythroid progenitor cells. Tyrosine phosphorylation experiments showed that several proteins in clone C5 cells were rapidly phosphorylated on tyrosine residues in response to Ep, one being the EpR itself. The proportion of cell surface EpRs tyrosine phosphorylated in response to Ep was substantial, reaching a maximum of approximately 10% within 30 minutes of incubation at 37 degrees C. A comparison of Ep- and murine interleukin-3 (mIL-3)-induced tyrosine phosphorylation patterns in clone C5 cells showed that both growth factors stimulated the tyrosine phosphorylation of proteins with molecular weights of 135, 93, 70, and 55 Kd. This could suggest that the Ep and mIL-3 receptors are capable of using the same tyrosine kinase in these cells.

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