Tumor Necrosis Factor-α Mediates Both Apoptotic Cell Death and Cell Proliferation in a Human Hematopoietic Cell Line Dependent on Mitotic Activity and Receptor Subtype Expression
| Autor: | Gregory T. Baxter, Peter Vandenabeele, David J. MacEwan, Orla J. Jupp, Richard C. Kuo |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
DNA Replication
Cell Survival medicine.medical_treatment Cell Mitosis Apoptosis Biology Biochemistry Receptors Tumor Necrosis Factor Cell Line Antigens CD Tumor Cells Cultured medicine Humans Receptors Tumor Necrosis Factor Type II Molecular Biology Tumor Necrosis Factor-alpha Cell growth Growth factor Cell Biology Hematopoietic Stem Cells Cell biology medicine.anatomical_structure Receptors Tumor Necrosis Factor Type I Cell culture Tumor necrosis factor alpha Signal transduction Cell Division Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 274:9539-9547 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.14.9539 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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