Interferon-α (IFN-α) inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF) expression at the post-transcriptional level in murine bone marrow stromal cells

1995 ◽  
Vol 91 (1) ◽  
pp. 8-14 ◽  
Author(s):  
Gerhard Goullner ◽  
M. Javad Aman ◽  
Hans Peter Steffens ◽  
Christoph Huber ◽  
Christian Peschel ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Interferon Α ◽  
Transcriptional Level ◽  
Murine Bone Marrow ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals cAMP analogues downregulate the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) in human bone marrow stromal cellsin vitro

1998 ◽  
Vol 7 (3) ◽  
pp. 195-199 ◽  
Author(s):  
G. Bug ◽  
J. Aman ◽  
C. Huber ◽  
C. Peschel ◽  
H. G. Derigs
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Inhibitory Effect ◽  
Marrow Stromal Cells ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The stimulation of granulocyte macrophage-colony stimulating factor (GM-CSF) by interleukin-1 (IL-1) has been shown to be counteracted in different mesenchymal cell systems by cyclic adenosine monophosphate (cAMP) agonists. The aim of this study was the evaluation of different cAMP agonists on GM-CSF expression in human bone marrow stromal cells. Incubation of secondary haematopoietic progenitor cell deprived human stromal cell cultures with IL-1 or TNF- α induced GM-CSF protein expression in culture supernatants and GM-CSFmRNA in adherent stromal cells. The coincubation with 8-bromo-cAMP (8BrcAMP), a water soluble cAMP analogue, inhibited this GM-CSF stimulation at the protein and the m RNA level. This effect was dose dependent with a maximal inhibition of about 65% occurring at a 8BrcAMP concentration of 0.75 mM. In addition to 8BrcAMP, other cAMP agonists such as dibutyryl-cAMP, forskolin, pertussis toxin, or prostaglandin E2(PGE2) had the same inhibitory effect on GM-CSF stimulation by IL-1. Coincubation with the cyclooxygenase inhibitor indomethacin had no significant influence on GM-CSF expression in stromal cells. Our results provide evidence that the previously described inhibitory effect of cAMP agonist PGE2on haematopoietic progenitor cellsin vivois, at least in part, mediated by modulating the expression of GMCSF in bone marrow stromal cells.

scholarly journals Retinoids (all-trans and 9-cis retinoic acid) stimulate production of macrophage colony-stimulating factor and granulocyte-macrophage colony- stimulating factor by human bone marrow stromal cells

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4107-4115 ◽  
Author(s):  
H Nakajima ◽  
M Kizaki ◽  
A Sonoda ◽  
S Mori ◽  
K Harigaya ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Retinoic Acid ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Human Bone ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Retinoic acids (RAs) exert pleiotropic effects on cellular growth and differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell lines and cells from patients with acute myelogenous leukemia (AML) in vitro. Despite information on the effects of RAs on hematopoietic cells, little is known about how RAs act on the hematopoietic microenvironment, especially on bone marrow stromal cells. Based on recent observations that various cytokines produced mainly by bone marrow stromal cells regulate hematopoiesis, we analyzed the effects of RAs on cytokine production by these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell line KM101, which produces macrophage colony-stimulating factor (M-CSF) and granulocyte- macrophage colony-stimulating factor (GM-CSF) constitutively, enhanced mRNA levels of both cytokines in a dose-dependent manner. Both RAs also stimulated M-CSF production from primary cultures of human bone marrow stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-alpha mRNA expression in a dose-dependent manner, but did not affect levels of RAR-alpha mRNA. These findings may have important biologic implications for both the role of RAs in hematopoiesis and the therapeutic effects of ATRA on the hematopoietic microenvironment in patients with acute promyelocytic leukemia (APL).

scholarly journals In Vitro Secretion of Cytokines by Human Bone Marrow: Effects of Age and Estrogen Status1

1998 ◽  
Vol 83 (6) ◽  
pp. 2043-2051
Author(s):  
Domingo Cheleuitte ◽  
Shuichi Mizuno ◽  
Julie Glowacki
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cytokine Production ◽  
Marrow Stromal Cells ◽  
Colony Stimulating Factor ◽  
Constitutive Secretion ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

It has been proposed that cytokines mediate the acceleration of bone loss following menopause. Because of the intimate relationship between bone marrow stromal cells and bone tissue, it is possible that marrow cells and their products contribute to the bone microenvironment and influence the regulation of bone cell differentiation and activity. We examined the production of cytokines by bone marrow stromal cells from a total of 37 women and 15 men undergoing total hip replacement for noninflammatory joint disease. Low-density mononuclear cells were isolated from bone marrow and were cultured in phenol red-free αMEM medium supplemented with 10% FBS and antibiotics. Constitutive secretion of interleukin-6 (IL-6) was positively correlated with age in a series of 8 women and 5 men measured by bioassay (r = 0.98; P < 0.01) and in a series of 18 women and 10 men measured by immunoassay (r = 0.56; P < 0.01). The pattern of cytokine production by bone marrow stromal cells was examined in detail in 23 postmenopausal women, aged 49–88 yr. Basal secretion of immunoreactive IL-6 and IL-11, but not granulocyte-macrophage colony-stimulating factor, increased with time in culture. Exogenous IL-1β stimulated secretion of IL-6 and IL-11 in a saturable, dose-dependent manner. Secretion of soluble IL-6 receptor was not correlated with secretion of IL-6, either constitutively or in the presence of IL-1β. In 4 of 14 samples, IL-1β also stimulated secretion of granulocyte-macrophage colony-stimulating factor. IL-1β was undetectable in 7 of 9 cultures during the 2-week culture period. IL-6 did not stimulate secretion of IL-1β in the 7 cultures tested. Cells were dependent upon serum for viability and growth and were not sustained by a serum substitute (1% insulin-transferrin-selenium-BSA). Cells grown in medium with 10% FBS and supplemented with 1% insulin-transferrin-selenium-BSA secreted 10-fold more IL-6 than cells grown in serum alone. Marrow from 7 women receiving estrogen replacement therapy showed lower constitutive secretion of IL-6 (75%; P < 0.006) and IL-11 (43%; P< 0.05) than marrow from age-matched controls and had blunted stimulation of IL-6 and IL-11 secretion by exogenous IL-1β. These data indicate distinct patterns of cytokine production by human marrow stromal cultures dependent upon age and estrogen status.

scholarly journals Nitric Oxide Donor Increases Osteoprotegerin Production and Osteoclastogenesis Inhibitory Activity in Bone Marrow Stromal Cells from Ovariectomized Rats

Endocrinology ◽  
2004 ◽  
Vol 145 (5) ◽  
pp. 2148-2156 ◽  
Author(s):  
Feng-Sheng Wang ◽  
Ching-Jen Wang ◽  
Yeung-Jen Chen ◽  
Yu-Ting Huang ◽  
Hui-Chen Huang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells ◽  
Ovariectomized Rats ◽  
Colony Stimulating Factor ◽  
No Donor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Nitric oxide (NO) has emerged as a potent regulator useful in alleviating estrogen deficiency bone loss. Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) play important roles in regulating osteoclastogenesis. Although recent studies have reported NO donor attenuation of bone loss, the effect of NO donor on OPG and RANKL expression of osteogenic stromal cells and bone microenvironment in ovariectomized rats is not fully understood. Here, we showed that optimal NO donor treatment [2,2′-(hydroxynitrosohydrazino)bis-ethanamine; 15 μm] increased OPG, but not RANKL, levels in bone marrow stromal cells from ovariectomized rats. NO donor augmentation of OPG synthesis was transcriptionally mediated. The stimulatory action of NO donor on OPG expression appeared to be regulated by tyrosine kinase-dependent activation of Cbfa1/Runx2 binding to the OPG promoter, because cell cultures pretreated with tyrosine kinase inhibitor (herbimycin A), but not with protein kinase A inhibitor (calphostain C) or protein kinase C inhibitor [(Rp)-cAMP] significantly reduced NO-augmented Runx2 activation and OPG levels. Conditioned medium from NO donor-treated cells inhibited macrophage-colony-stimulating factor and RANKL-induced osteoclast formation of macrophage-colony-stimulating factor-dependent bone marrow macrophages. Neutralization with anti-OPG antibodies abolished the inhibitory effect of conditioned medium on osteoclastogenesis. Immunohistochemical observation also showed that 2,2′-(hydroxynitrosohydrazino)bis-ethanamine increased OPG expression of osteochondral cells located at metaphyseal endosteum and calcified cartilage of proximal femurs in ovariectomized rats. These findings suggest that NO donor can be an alternative pharmacological strategy for regulating bone resorption.

scholarly journals Cloning and expression of unique murine macrophage colony-stimulating factor transcripts

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3478-3486 ◽  
Author(s):  
K Pogue-Geile ◽  
MA Sakakeeny ◽  
JL Panza ◽  
SL Sell ◽  
JS Greenberger
Keyword(s):  
Bone Marrow ◽  
Cell Line ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Bone Marrow Stromal Cell ◽  
Marrow Stromal Cells ◽  
Ionizing Irradiation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Cocultivation of cells from the gamma-irradiated D2XRII murine bone marrow stromal cell line with an interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent hematopoietic progenitor cell line FDC-P1JL26 stimulates the emergence of factor-independent hematopoietic cell sublines. Several lines of evidence suggested that M-CSF or a protein antigenically related to M-CSF, termed leukemogenic stromal factor (LSF), that was expressed by D2XRII cells may have played a role in the emergence of the factor-independent sublines. In an effort to isolate a factor antigenically related to M-CSF, molecular clones were isolated from a D2XRII cDNA library that hybridized to a mouse M-CSF genetic probe. Two of these molecular clones, designated 60.8.2 and 6452, contained an 885-bp deletion in the M-CSF coding region. Such a cDNA clone has not been previously described in the mouse, but a cDNA clone homologous to it has been isolated from a human pancreatic tumor cell line, MIA-PaCa-2. Three transcripts (4.8, 3.4, and 1.8 kb) were detected that hybridized to an oligonucleotide probe that was specific to RNA transcripts containing the 60.8.2 deletion. The level of the 1.8-kb transcript was not detectably induced by ionizing irradiation; however, the levels of the 4.8-kb and 3.4-kb transcripts and two other M-CSF transcripts of sizes to 4.4 kb and 2.3 kb showed a 1.4- to 2.2-fold increase after gamma irradiation. Reverse transcription-polymerase chain reaction showed that the deletion-specific transcript(s) was detected in multiple mouse bone marrow stromal cell lines and in normal mouse tissues. The present studies establish the existence of an increased spectrum of murine M-CSF transcripts in bone marrow stromal cells and other tissues. This complexity of transcripts along with their increased accumulation after irradiation provides additional evidence for a role of proteins encoded by M-CSF transcripts in the response of bone marrow stromal cells to ionizing irradiation.

scholarly journals Premature expression of the macrophage colony-stimulating factor receptor on a multipotential stem cell line does not alter differentiation lineages controlled by stromal cells used for coculture.

1991 ◽  
Vol 173 (5) ◽  
pp. 1267-1279 ◽  
Author(s):  
T Kinashi ◽  
K H Lee ◽  
M Ogawa ◽  
K Tohyama ◽  
K Tashiro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stromal Cells ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Colony Stimulating Factor ◽  
Stem Cell Line ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

We are interested to know whether expression of a lineage-specific growth factor receptor is deterministic to lineage commitment during hematopoiesis. For this purpose, we introduced the human c-fms gene into the multipotential stem cell clone LyD9 and two myeloid progenitor clones, L-GM3 and L-G3, cells that differentiate in response to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte (G)-CSF, respectively. Although LyD9 cells have differentiation potential to become macrophages, c-fms transfectants of LyD9 and L-GM3 cells did not differentiate in response to human macrophage (M)-CSF. However, c-fms transfectants of L-G3 cells differentiated to neutrophils in response to human M-CSF. These results indicate that the M-CSF receptor requires a specific signal transduction pathway to exert its differentiational and proliferative effects. Furthermore, the M-CSF receptor can convey a granulocyte-type differentiation signal possibly by cooperating with the G-CSF receptor signal transduction pathway. The c-fms-transfected LyD9 cells as well as the original LyD9 cells differentiated predominantly into GM-CSF- and G-CSF-responsive cells by coculturing with PA6 and ST2 stromal cells, respectively. The results indicate that differentiation lineage is not affected by premature expression of the M-CSF receptor. Instead, the stromal cell used for coculture apparently controls lineage-selective differentiation of the multi-potential stem cell line.

Interferon-γ switches monocyte differentiation from dendritic cells to macrophages

Blood ◽  
2003 ◽  
Vol 101 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Yves Delneste ◽  
Peggy Charbonnier ◽  
Nathalie Herbault ◽  
Giovanni Magistrelli ◽  
Gersende Caron ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Interferon Γ ◽  
Transcriptional Level ◽  
Colony Stimulating Factor ◽  
Monocyte Differentiation ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Ifn Γ ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Human monocytes differentiate into dendritic cells (DCs) or macrophages according to the nature of environmental signals. Monocytes stimulated with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL-4) yield DCs. We tested here whether interferon-γ (IFN-γ), a potent activator of macrophages, may modulate monocyte differentiation. Addition of IFN-γ to IL-4 plus GM-CSF–stimulated monocytes switches their differentiation from DCs to CD14−CD64+ macrophages. IFN-γ increases macrophage colony-stimulating factor (M-CSF) and IL-6 production by IL-4 plus GM-CSF–stimulated monocytes by acting at the transcriptional level and acts together with IL-4 to up-regulate M-CSF but not IL-6 production. IFN-γ also increases M-CSF receptor internalization. Results from neutralizing experiments show that both M-CSF and IL-6 are involved in the ability of IFN-γ to skew monocyte differentiation from DCs to macrophages. Finally, this effect of IFN-γ is limited to early stages of differentiation. When added to immature DCs, IFN-γ up-regulates IL-6 but not M-CSF production and does not convert them to macrophages, even in the presence of exogenous M-CSF. In conclusion, IFN-γ shifts monocyte differentiation to macrophages rather than DCs through autocrine M-CSF and IL-6 production. These data show that IFN-γ controls the differentiation of antigen-presenting cells and thereby reveals a new mechanism by which IFN-γ orchestrates the outcome of specific immune responses.

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