title: Nuclear factor-kappaB/Rel is apoptogenic in cytokine withdrawal-induced programmed cell death.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: U S
authors.initials: US
authors.lastname: Sohur
authors.forename: C L
authors.initials: CL
authors.lastname: Chen
authors.forename: D J
authors.initials: DJ
authors.lastname: Hicks
authors.forename: F E
authors.initials: FE
authors.lastname: Yull
authors.forename: L D
authors.initials: LD
authors.lastname: Kerr
mesh_terms: 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
chemical_list: D016207:Cytokines; D016328:NF-kappa B