|
|
 Previous Article | Table of Contents | Next Article 
Transforming Growth Factor- 1 Abrogates Fas-Induced Growth Suppression and Apoptosis of Murine Bone Marrow Progenitor Cells
Ingunn Dybedal,
Fengan Guan,
Ole Johan Borge,
Ole Petter Veiby,
Veslemøy Ramsfjell,
Shigekazu Nagata, and
Sten Eirik W. Jacobsen
From the Hipple Cancer Research Center, Dayton, OH; Stem Cell Laboratory, Section for Molecular Medicine and Gene Therapy, the Department of Internal Medicine, University Hospital of Lund, Lund, Sweden; and Osaka Bioscience Institute, Osaka, Japan.
Fas, a member of the tumor necrosis factor (TNF ) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon- (IFN-) and TNF- can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Transforming growth factor- 1 (TGF-1 ) is an essential anti-inflammatory cytokine, thought to play a key role in regulating hematopoiesis. In the present studies we investigated whether TGF-1 might regulate growth suppression and apoptosis of murine hematopoietic progenitor cells signaled through Fas. In the presence of TNF, activation of Fas almost completely blocked clonogenic growth of lineage-depleted (Lin-) bone marrow (BM) progenitor cells in response to granulocyte-macrophage colony-stimulating factor (GM-CSF ), CSF-1, or a combination of multiple cytokines. Whereas TGF-1 alone had no effect or stimulated growth in response to these cytokines, it abrogated Fas-induced growth suppression. Single-cell studies and delayed addition of TGF-1 showed that the ability of TGF-1 to inhibit Fas-induced growth suppression was directly mediated on the progenitor cells and not indirect through potentially contaminating accessory cells. Furthermore, TGF-1 blocked Fas-induced apoptosis of Lin- BM cells, but did not affect Fas-induced apoptosis of thymocytes. TGF-1 also downregulated the expression of Fas on Lin- BM cells. Thus, TGF-1 potently and directly inhibits activation-dependent and Fas-mediated growth suppression and apoptosis of murine BM progenitor cells, an effect that appears to be distinct from its ability to induce progenitor cell-cycle arrest. Consequently, TGF-1 might act to protect hematopoietic progenitor cells from enhanced Fas expression and function associated with proinflammatory responses.
Blood, Vol. 90 No. 9 (November 1), 1997:
pp. 3395-3403
© 1997 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Pearl-Yafe, J. Stein, E. S. Yolcu, D. L. Farkas, H. Shirwan, I. Yaniv, and N. Askenasy
Fas Transduces Dual Apoptotic and Trophic Signals in Hematopoietic Progenitors
Stem Cells,
December 1, 2007;
25(12):
3194 - 3203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-M. Park, S. Kim, J.-S. Choi, D.-Y. Hur, W.-J. Lee, M.-S. Lee, J. Choe, and T. H. Lee
TGF-{beta} Inhibits Fas-Mediated Apoptosis of a Follicular Dendritic Cell Line by Down-Regulating the Expression of Fas and Caspase-8: Counteracting Role of TGF-{beta} on TNF Sensitization of Fas-Mediated Apoptosis
J. Immunol.,
May 15, 2005;
174(10):
6169 - 6175.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S.-M. Park, H.-Y. Park, and T. H. Lee
Functional Effects of TNF-{alpha} on a Human Follicular Dendritic Cell Line: Persistent NF-{kappa}B Activation and Sensitization for Fas-Mediated Apoptosis
J. Immunol.,
October 15, 2003;
171(8):
3955 - 3962.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Bryder, V. Ramsfjell, I. Dybedal, K. Theilgaard-Monch, C.-M. Hogerkorp, J. Adolfsson, O. J. Borge, and S. E. W. Jacobsen
Self-Renewal of Multipotent Long-Term Repopulating Hematopoietic Stem Cells Is Negatively Regulated by Fas and Tumor Necrosis Factor Receptor Activation
J. Exp. Med.,
October 1, 2001;
194(7):
941 - 952.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Moreau, M. Leite-de-Moraes, S. Ezine, J. P. Di Santo, M. Dy, and E. Schneider
Natural killer cell-dependent apoptosis of peripheral murine hematopoietic progenitor cells in response to Fas cross-linking: involvement of tumor necrosis factor-{alpha}
Blood,
May 15, 2001;
97(10):
3069 - 3074.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Chodon, T. Sugihara, H. H. Igawa, E. Funayama, and H. Furukawa
Keloid-Derived Fibroblasts Are Refractory to Fas-Mediated Apoptosis and Neutralization of Autocrine Transforming Growth Factor-{beta}1 Can Abrogate this Resistance
Am. J. Pathol.,
November 1, 2000;
157(5):
1661 - 1669.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. O. Fortunel, A. Hatzfeld, and J. A. Hatzfeld
Transforming growth factor-beta : pleiotropic role in the regulation of hematopoiesis
Blood,
September 15, 2000;
96(6):
2022 - 2036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Inman and M. J. Allday
Apoptosis Induced by TGF-{beta}1 in Burkitt's Lymphoma Cells Is Caspase 8 Dependent But Is Death Receptor Independent
J. Immunol.,
September 1, 2000;
165(5):
2500 - 2510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P Batard, M. Monier, N Fortunel, K Ducos, P Sansilvestri-Morel, T Phan, A Hatzfeld, and J. Hatzfeld
TGF-(beta)1 maintains hematopoietic immaturity by a reversible negative control of cell cycle and induces CD34 antigen up-modulation
J. Cell Sci.,
January 2, 2000;
113(3):
383 - 390.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Jenkins, M. Keir, and J. M. McCune
Fas Is Expressed Early in Human Thymocyte Development But Does Not Transmit an Apoptotic Signal
J. Immunol.,
August 1, 1999;
163(3):
1195 - 1204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V.P. Kale and L.S. Limaye
Stimulation of Adult Human Bone Marrow by Factors Secreted by Fetal Liver Hematopoietic Cells: In Vitro Evaluation Using Semisolid Clonal Assay System
Stem Cells,
March 1, 1999;
17(2):
107 - 116.
[Abstract]
[Full Text]
|
|
|
|
|
