In:
Blood, American Society of Hematology, Vol. 90, No. 9 ( 1997-11-01), p. 3395-3403
Abstract:
Fas, a member of the tumor necrosis factor (TNF ) receptor superfamily is a critical downregulator of cellular immune responses. Proinflammatory cytokines like interferon-γ (IFN-γ) and TNF-α can induce Fas expression and render hematopoietic progenitor cells susceptible to Fas-induced growth suppression and apoptosis. Transforming growth factor-β1 (TGF-β1 ) is an essential anti-inflammatory cytokine, thought to play a key role in regulating hematopoiesis. In the present studies we investigated whether TGF-β1 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-β1 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-β1 showed that the ability of TGF-β1 to inhibit Fas-induced growth suppression was directly mediated on the progenitor cells and not indirect through potentially contaminating accessory cells. Furthermore, TGF-β1 blocked Fas-induced apoptosis of Lin− BM cells, but did not affect Fas-induced apoptosis of thymocytes. TGF-β1 also downregulated the expression of Fas on Lin− BM cells. Thus, TGF-β1 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-β1 might act to protect hematopoietic progenitor cells from enhanced Fas expression and function associated with proinflammatory responses.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood.V90.9.3395
Language:
English
Publisher:
American Society of Hematology
Publication Date:
1997
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
Permalink