TNF-alpha bidirectionally modulates the viability of primitive murine hematopoietic progenitor cells in vitro.
It is well established that TNF-alpha can induce apoptosis in many normal and transformed cell types. The effects of TNF-alpha on cytokine-induced proliferation and differentiation of normal hematopoietic progenitors have been characterized extensively, whereas little is known about how TNF-alpha can affect their viability. The present studies suggest, based on experiments using delayed addition of growth-promoting cytokines as well direct viability assays, that TNF-alpha bidirectionally affects the survival of individually cultured primitive Lin- Sca-1+ hematopoietic progenitors, in that stem cell factor (SCF)-, granulocyte-CSF-, IL-6-, and IL-11-induced survival is potently counteracted by TNF-alpha (42-86%), whereas TNF-alpha synergistically enhances IL-1alpha-induced survival up to threefold. The bidirectional effects of TNF-alpha on hematopoietic growth factor-induced survival of hematopoietic progenitors were reflected in that TNF-alpha enhanced apoptosis of Lin- Sca-1+ cells when combined with SCF, whereas TNF-alpha synergistically suppressed apoptosis in response to IL-1alpha.
Jacobsen
F W
FW
Department of Immunology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway.
Veiby
O P
OP
Stokke
T
T
Jacobsen
S E
SE
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D019089:Stem Cell Factor / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D017370:Interleukin-11; D015850:Interleukin-6; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor