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

Abstract 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.

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.

scholarly journals Differential regulation of chemokines by leukemia inhibitory factor, interleukin-6 and oncostatin M

1997 ◽  
Vol 51 (6) ◽  
pp. 1754-1760 ◽  
Author(s):  
Andrea Hartner ◽  
Margarete Goppelt-Struebe ◽  
Gertrud M. Hocke ◽  
R. Bernd Sterzel
Keyword(s):  
Interleukin 6 ◽  
Leukemia Inhibitory Factor ◽  
Differential Regulation ◽  
Oncostatin M ◽  
Inhibitory Factor

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 Induction of differentiation of WEHI-3B D+ leukemic cells transfected with differentiation-stimulating factor/leukemia inhibitory factor receptor cDNA

Blood ◽  
1995 ◽  
Vol 85 (1) ◽  
pp. 217-221 ◽  
Author(s):  
M Tomida
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Oncostatin M ◽  
Inhibitory Factor ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Leukemia Inhibitory Factor Receptor ◽  
Transfected Cells ◽  
Receptor Cdna ◽  
Induction Of Differentiation ◽  
Stimulating Factor

Differentiation-stimulating factor (D-factor)/leukemia inhibitory factor can induce the differentiation of mouse myeloid leukemia M1 cells and also stimulate proliferation of the interleukin-3 (IL-3)- dependent cell line, DA-1a. To determine whether D-factor can induce the differentiation of leukemia cells other than M1 cells, WEHI-3B D+ mouse myelomonocytic leukemia cells were transfected with a plasmid containing mouse D-factor receptor cDNA. Expression of D-factor receptor in transfected cells was determined by binding of [125]D- factor and analyzed by Scatchard's method. The transfected cells had high-affinity D-factor receptors with a dissociation constant of 100 to 200 pmol/L and binding sites per cell varied from 67 to 1,500 among several clones. The cells expressing a high level of D-factor receptor were induced to differentiate by D-factor; about 60% of the cells exhibited the ability to reduce nitroblue tetrazolium and expression of the differentiation antigen Mac-1 (CD11b) on the cell surface increased. The effect of cytokines, which induce the differentiation of M1 cells, on the transfected WEHI-3B cells was examined. The sensitivity to oncostatin M was identical to that against D-factor in the cells of each clone. Expression of D-factor receptor in WEHI-3B cells promoted sensitivity to IL-6 and granulocyte colony-stimulating factor (G-CSF). Induction of differentiation of the cells accompanied the suppression of proliferation. Treatment of the cells with D-factor for longer than 5 days resulted in 50% inhibition of growth. These results indicate that the stimulating effect of D-factor on the differentiation of malignant myeloid cells is not unique to M1 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 Leukemia inhibitory factor upregulates cytokine expression by a murine stromal cell line enabling the maintenance of highly enriched competitive repopulating stem cells

Blood ◽  
1996 ◽  
Vol 87 (11) ◽  
pp. 4618-4628 ◽  
Author(s):  
SJ Szilvassy ◽  
KP Weller ◽  
W Lin ◽  
AK Sharma ◽  
AS Ho ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Lines ◽  
Leukemia Inhibitory Factor ◽  
Stromal Cell ◽  
Cytokine Expression ◽  
Inhibitory Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Attempts to maintain or expand primitive hematopoietic stem cells in vitro without the concomitant loss of their differentiative and proliferative potential in vivo have largely been unsuccessful. To investigate this problem, we compared the ability of three cloned bone marrow (BM) stromal cell lines to support the growth of primitive Thy- 1lo Sca-1+H-2Khi cells isolated by fluorescence-activated cell sorting from the BM of Ly-5.2 mice treated 1 day previously with 5-fluo- rouracil. Sorted cells were highly enriched in cobblestone area-forming cells (CAFC), but their frequency was dependent on the stromal cell lines used in this assay (1 per 45 cells on SyS-1; 1 per 97 cells on PA6). In the presence of recombinant leukemia inhibitory factor (LIF), CAFC cloning efficiency was increased to 1 per 8 cells on SyS-1 and 1 per 11 cells on PA6, thus showing the high clonogenicity of this primitive stem cell population. More primitive stem cells with competitive repopulating potential were measured by injecting the sorted cells into lethally irradiated Ly-5.1 mice together with 10(5) radioprotective Ly-5.1 BM cells whose long-term repopulating ability has been “compromised” by two previous cycles of marrow transplantation and regeneration. Donor-derived lymphocytes and granulocytes were detected in 66% of animals injected with 50 sorted cells. To quantitate the maintenance of competitive repopulating units (CRU) by stromal cells, sorted cells were transplanted at limiting dilution before and after being cultured for 2 weeks on adherent layers of SyS-1, PA6, or S17 cells. CRU represented 1 per 55 freshly sorted cells. CRU could be recovered from cocultures supported by all three stromal cell lines, but their numbers were approximately-sevenfold less than on day 0. In contrast, the addition of LIF to stromal cultures improved CRU survival by 2.5-fold on S17 and PA6 cells (approximately two-fold to threefold decline), and enabled their maintenance on SyS-1. LIF appeared to act indirectly, because alone it did not support the proliferation of Thy- 1lo Sca-1+H-2Khi cells in stroma-free cultures. Polymerase chain reaction (RT-PCR) analysis revealed that Interleukin-1beta (IL-1 beta) IL-2, IL-6, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, transforming growth factors, LIF, and Steel Factor (SLF) mRNAs were upregulated in SyS-1 within 1 to 6 hours of LIF-stimulation. To determine if increased expression of SLF by LIF-stimulated SyS-1 cells could account for their capacity to support stem cells, sorted calls were cocultured on simian CV-E cells that were transfected with an expression vector encoding membrane-bound SLF, or supplemented with soluble SLF. In both cases, SLF synergized with IL-6 produced endogenously by CV-E cells enabling CAFC growth equivalent to that on LIF-stimulated SyS-1. CAFC development on LIF- stimulated SyS-1 could also be completely abrogated by an anti-SLF antibody. These data provide evidence for a role of LIF in the support of long-term repopulating stem cells by indirectly promoting cytokine expression by BM stroma. Furthermore, we have used quantitative assays to show a maintenance of CRU numbers, with retention of in vivo function following ex vivo culture.

Sign in / Sign up

Export Citation Format

Share Document