Nuclear factor-kappaB/Rel is apoptogenic in cytokine withdrawal-induced programmed cell death.
In the complex microenvironment where they evolve, developing cells undergo rapid programmed cell death (PCD) when cytokines that support them become limiting. The transcriptional mechanisms of cytokine-withdrawal apoptosis are poorly understood. In this report, we used early B-lymphocyte tissue culture and transgenic cells to demonstrate that nuclear factor-kappaB (NF-kappaB) promotes apoptosis during cytokine withdrawal-induced PCD. In the progenitor B lymphocyte model FL5.12, whereas NF-kappaB has an antiapoptotic function in response to tumor necrosis factor-alpha, cytokine withdrawal causes nuclear translocation of NF-kappaB/cRel, where it is apoptogenic. Inhibition of NF-kappaB activation delays cytokine withdrawal-induced PCD in both FL5.12 and transgenic early B cells. Additionally, reconstituting a bone marrow microenvironment ex vivo abrogates the differential apoptotic pattern between control and transgenic early B cells.
Sohur
U S
US
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Chen
C L
CL
Hicks
D J
DJ
Yull
F E
FE
Kerr
L D
LD
D017209:Apoptosis / Q000235:genetics*; D001402:B-Lymphocytes / Q000473:pathology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D020573:Genes, rel; D006801:Humans; D016328:NF-kappa B / Q000235:genetics*; D014158:Transcription, Genetic
D016207:Cytokines; D016328:NF-kappa B