Tumor necrosis factor-alpha mediates both apoptotic cell death and cell proliferation in a human hematopoietic cell line dependent on mitotic activity and receptor subtype expression.
J Biol Chem
; 274(14): 9539-47, 1999 Apr 02.
Article
em En
| MEDLINE
| ID: mdl-10092639
ABSTRACT
The TF-1 human erythroleukemic cell line exhibits opposing physiological responses toward tumor necrosis factor-alpha (TNF) treatment, dependent upon the mitotic state of the cells. Mitotically active cells in log growth respond to TNF by rapidly undergoing apoptosis whereas TNF exposure stimulates cellular proliferation in mitotically quiescent cells. The concentration-dependent TNF-induced apoptosis was monitored by cellular metabolic activity and confirmed by both DNA epifluorescence and DNA fragmentation. Moreover, these responses could be detected by measuring extracellular acidification activity, enabling rapid prediction (within approximately 1.5 h of TNF treatment) of the fate of the cell in response to TNF. Growth factor resupplementation of quiescent cells, resulting in reactivation of cell cycling, altered TNF action from a proliferative stimulus to an apoptotic signal. Expression levels of the type II TNF receptor subtype (p75TNFR) were found to correlate with sensitivity to TNF-induced apoptosis. Pretreatment of log growth TF-1 cells with a neutralizing anti-p75TNFR monoclonal antibody inhibited TNF-induced apoptosis by greater than 80%. Studies utilizing TNF receptor subtype-specific TNF mutants and neutralizing antisera implicated p75TNFR in TNF-dependent apoptotic signaling. These data show a bifunctional physiological role for TNF in TF-1 cells that is dependent on mitotic activity and controlled by the p75TNFR.
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Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Antígenos CD
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Fator de Necrose Tumoral alfa
/
Apoptose
/
Receptores do Fator de Necrose Tumoral
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Mitose
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article