Decorin inhibits macrophage colony-stimulating factor proliferation of macrophages and enhances cell survival through induction of p27Kip1 and p21Waf1

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2124-2133 ◽  
Author(s):  
Jordi Xaus ◽  
Mònica Comalada ◽  
Marina Cardó ◽  
Annabel F. Valledor ◽  
Antonio Celada
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Cell Survival ◽  
Interferon Γ ◽  
Colony Stimulating Factor ◽  
Inhibition Of Proliferation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Erk Activity ◽  
Stimulating Factor

Decorin is a small proteoglycan that is ubiquitous in the extracellular matrix of mammalian tissues. It has been extensively demonstrated that decorin inhibits tumor cell growth; however, no data have been reported on the effects of decorin in normal cells. Using nontransformed macrophages from bone marrow, results of this study showed that decorin inhibits macrophage colony-stimulating factor (M-CSF)–dependent proliferation by inducing blockage at the G1 phase of the cell cycle without affecting cell viability. In addition, decorin rescues macrophages from the induction of apoptosis after growth factor withdrawal. Decorin induces the expression of the cdk inhibitors p21Waf1 and p27Kip1. Using macrophages from mice where these genes have been disrupted, inhibition of proliferation mediated by decorin is related to p27Kip1 expression, whereas p21Waf1expression is necessary to protect macrophages from apoptosis. Decorin also inhibits M-CSF–dependent expression of MKP-1 and extends the kinetics of ERK activity, which is characteristic when macrophages become activated instead of proliferating. The effect of decorin on macrophages is not due to its interaction with epidermal growth factor or interferon-γ receptors. Furthermore, decorin increases macrophage adhesion to the extracellular matrix, and this may be partially responsible for the expression of p27Kip1 and the modification of ERK activity, but not for the increased cell survival.

Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors

1992 ◽  
Vol 262 (4) ◽  
pp. C876-C881 ◽  
Author(s):  
M. Pinzani ◽  
H. E. Abboud ◽  
L. Gesualdo ◽  
S. L. Abboud
Keyword(s):  
Growth Factor ◽  
Constitutive Expression ◽  
Liver Fat ◽  
Northern Analysis ◽  
Mrna Levels ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Macrophage colony-stimulating factor (M-CSF) selectively promotes mononuclear phagocyte survival, proliferation, and differentiation. The production of this factor within the liver may be necessary to support the relatively long-term survival of circulating monocytes as they migrate into tissues and differentiate into macrophages. We studied the constitutive expression and the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on M-CSF mRNA levels and secretion of M-CSF in murine liver fat-storing cells (FSC), vascular pericytes likely involved in the development of liver fibrosis. By Northern analysis, using a murine M-CSF cDNA, FSC constitutively express two major transcripts of 4.4 and 2.2 kb, similar to those detected in mouse L cells, used as a control. Exposure to 10 ng/ml PDGF or bFGF increased M-CSF mRNA levels. Peak effects were observed at 3 and 6 h for PDGF and bFGF, respectively, returning to baseline levels by 12 h. Under basal conditions, detectable amounts of M-CSF, measured by radioimmunoassay, were found in cell supernatants conditioned for 8 and 24 h. PDGF and bFGF markedly stimulated the release of M-CSF as early as 8 h, an effect persisting for at least 24 h. These findings suggest that liver FSC release M-CSF upon stimulation by PDGF and bFGF and may contribute to the activation of resident or infiltrating cells in inflammatory liver diseases.

scholarly journals Heparin inhibits the expression of interleukin-11 and granulocyte- macrophage colony-stimulating factor in primate bone marrow stromal fibroblasts through mRNA destabilization

Blood ◽  
1995 ◽  
Vol 86 (7) ◽  
pp. 2526-2533 ◽  
Author(s):  
L Yang ◽  
YC Yang
Keyword(s):  
Bone Marrow ◽  
Extracellular Matrix ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Extracellular Matrix Components ◽  
Macrophage Colony Stimulating Factor ◽  
Mrna Destabilization ◽  
Matrix Components ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Interactions between different cytokines, extracellular matrix components, and various cell types inside the bone marrow microenvironment are believed to play important roles in the regulation of hematopoiesis. We observed that both interleukin-1 (IL-1) and 12-O- tetradecanoylphorbol-13-acetate (TPA) can stimulate the expression of IL-11 and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in a primate bone marrow stromal fibroblast cell line, PU-34. We also found that IL-1 or TPA-stimulated IL-11 and GM-CSF expression in PU-34 cells can be abolished by heparin, a class of molecules related to extracellular matrix components, glycosaminoglycans. Because the growth inhibitory signals provided by extracellular factors were less understood, the mechanisms of heparin inhibition of IL-11 and GM-CSF gene expression were further investigated. Our data demonstrate for the first time that heparin did not alter the transcription of endogenous IL-11 and GM-CSF genes or an exogenous IL-11 promoter construct containing an AP-1 sequence. Instead, heparin facilitated the degradation of the corresponding mRNAs. Through RNA gel shift assays, heparin-mediated mRNA destabilization was tentatively linked to its competition for mRNA binding proteins both in the cell-free system and in intact cells. Collectively, our findings suggest that varying degrees of heparin inhibition may provide a novel mechanism for the regulation of cytokine expression during the growth and differentiation of different lineages of hematopoietic cells.

scholarly journals Macrophage Colony-stimulating Factor Promotes Cell Survival through Akt/Protein Kinase B

1999 ◽  
Vol 274 (37) ◽  
pp. 26393-26398 ◽  
Author(s):  
Todd W. Kelley ◽  
Mandy M. Graham ◽  
Andrea I. Doseff ◽  
Richard W. Pomerantz ◽  
Sey M. Lau ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Survival ◽  
Protein Kinase B ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals Vascular Smooth Muscle Cell–Derived Transforming Growth Factor-β Promotes Maturation of Activated, Neointima Lesion–Like Macrophages

2014 ◽  
Vol 34 (4) ◽  
pp. 877-886 ◽  
Author(s):  
Allison Ostriker ◽  
Henrick N. Horita ◽  
Joanna Poczobutt ◽  
Mary C.M. Weiser-Evans ◽  
Raphael A. Nemenoff
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Conditioned Media ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Objective— To define the contribution of vascular smooth muscle cell (SMC)–derived factors to macrophage phenotypic modulation in the setting of vascular injury. Approach and Results— By flow cytometry, macrophages (M4) were the predominant myeloid cell type recruited to wire-injured femoral arteries, in mouse, compared with neutrophils or eosinophils. Recruited macrophages from injured vessels exhibited a distinct expression profile relative to circulating mononuclear cells (peripheral blood monocytes; increased: interleukin-6, interleukin-10, interleukin-12b, CC chemokine receptor [CCR]3, CCR7, tumor necrosis factor-α, inducible nitric oxide synthase, arginase 1; decreased: interleukin-12a, matrix metalloproteinase [MMP]9). This phenotype was recapitulated in vitro by maturing rat bone marrow cells in the presence of macrophage-colony stimulating factor and 20% conditioned media from cultured rat SMC (sMφ) compared with maturation in macrophage-colony stimulating factor alone (M0). Recombinant transforming growth factor (TGF)-β1 recapitulated the effect of SMC conditioned media. Macrophage maturation studies performed in the presence of a pan-TGF-β neutralizing antibody, a TGF-β receptor inhibitor, or conditioned media from TGF-β–depleted SMCs confirmed that the SMC-derived factor responsible for macrophage activation was TGF-β. Finally, the effect of SMC-mediated macrophage activation on SMC biology was assessed. SMCs cocultured with sMφ exhibited increased rates of proliferation relative to SMCs cultured alone or with M0 macrophages. Conclusions— SMC-derived TGF-β modulates the phenotype of maturing macrophages in vitro, recapitulating the phenotype found in vascular lesions in vivo. SMC-modulated macrophages induce SMC activation to a greater extent than control macrophages.

scholarly journals Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 971-979 ◽  
Author(s):  
T Tsuda ◽  
D Wong ◽  
J Dolovich ◽  
J Bienenstock ◽  
J Marshall ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Colony Stimulating Factor ◽  
Nerve Growth ◽  
Basophilic Cell ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

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