Both TNF receptors are required for direct TNF‐mediated cytotoxicity in microvascular endothelial cells
| Autor: | Rudolf Lucas, Gabriel Núñez, Georges E. Grau, Michael S. Pepper, Wim A. Buurman, Christine Giroud, Yves Donati, Lucie Fransen, Peter M. Suter, Marusa Hribar, Irene Garcia, Stefano J. Mandriota |
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| Přispěvatelé: | Algemene Heelkunde, RS: NUTRIM School of Nutrition and Translational Research in Metabolism |
| Rok vydání: | 1998 |
| Předmět: |
Male
endocrine system Bcl-X Protein Immunology bcl-X Protein Endothelium Vascular/cytology/ drug effects Proto-Oncogene Proteins c-bcl-2/physiology Apoptosis Bcl-xL ddc:616.07 Receptors Tumor Necrosis Factor Mice Antigens CD Animals Humans Receptors Tumor Necrosis Factor Type II Immunology and Allergy Cytotoxicity Receptor Incubation Tumor Necrosis Factor-alpha/ pharmacology biology Tumor Necrosis Factor-alpha Dactinomycin/pharmacology Molecular biology Cell biology Apoptosis/ drug effects Endothelial stem cell Proto-Oncogene Proteins c-bcl-2 Receptors Tumor Necrosis Factor Type I Antigens CD/ physiology Toxicity Dactinomycin Mice Inbred CBA cardiovascular system biology.protein Receptors Tumor Necrosis Factor/ physiology Tumor necrosis factor alpha Endothelium Vascular |
| Zdroj: | European Journal of Immunology, 28(11), 3577-3586. Wiley European Journal of Immunology, Vol. 28, No 11 (1998) pp. 3577-3586 |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/(sici)1521-4141(199811)28:11<3577::aid-immu3577>3.0.co;2-# |
| Popis: | Department of Anaesthesiology, Pharmacology and Surgical Intensive Care, University Medical Center, University of Geneva, Switzerland. lucas@cmu.unige.chThe conditions under which tumor necrosis factor-alpha (TNF) induces apoptosis in primary microvascular endothelial cells (MVEC) were investigated. In the absence of sensitizing agents, TNF induced apoptosis after 3 days of incubation in confluent MVEC. In contrast, upon addition of the transcriptional inhibitor actinomycin D (Act. D), confluence was no longer required and apoptosis occurred already after 16 h. To assess the role of either TNF receptor (TNFR) type in apoptosis, MVEC isolated from mice genetically deficient in TNFR1 (Tnfr1o mice) or TNFR2 (Tnfr2o mice) were incubated with TNF in the presence or absence of Act. D. Under sensitized conditions, Tnfr2o MVEC were lysed like controls, whereas Tnfr1o MVEC were completely resistant, indicating an exclusive role for TNFR1. In contrast, in the absence of Act. D, confluent monolayers of wild-type cells were lysed by TNF, but both Tnfr1o and Tnfr2o MVEC were resistant to TNF-mediated toxicity, indicating a requirement for both TNFR types. Overexpression of the anti-apoptotic protein bcl-xL in MVEC led to a protection against the direct, but not the sensitized cytotoxicity of TNF. In conclusion, in pathophysiologically relevant conditions, both TNFR appear to be required for TNF-induced apoptosis in MVEC. |
| Databáze: | OpenAIRE |
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