IFN-gamma upregulates anti-apoptotic gene expression and inhibits apoptosis in IL-3-dependent hematopoietic cells.
IFN-gamma is a cytokine which functions in a wide range of biological activities by inducing a number of early and delayed genes. In murine IL-3-dependent cell lines BAF-B03 and 32D, IFN-gamma upregulated bag-1 and bcl-xL gene expression. These cells revealed prolonged cell survival against IL-3-deprivation by IFN-gamma stimulation. In contrast, human myeloma cell line RPMI8226, despite expression of IFN-gamma receptor, showed neither induction of their expressions nor prolonged cell survival against serum starvation-induced apoptosis by IFN-gamma stimulation. Gene-transfer-mediated overexpression of BAG-1 protein in BAF-B03 cells led to prolonged cell survival against IL-3-deprived apoptosis compared with control BAF-B03 transfectants, indicating that levels of BAG-1 expression are crucial for cell survival in BAF-B03 cells. Taken together, these studies suggest that induction of anti-apoptotic gene expression is a crucial factor for the anti-apoptotic function of IFN-gamma in IL-3-dependent immature hematopoietic cells.
Sekiya
M
M
First Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
Adachi
M
M
Takayama
S
S
Reed
J C
JC
Imai
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002352:Carrier Proteins / Q000096:biosynthesis; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D014157:Transcription Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D007377:Interleukin-3; D014157:Transcription Factors; D007371:Interferon-gamma