Activation of Nuclear Factor κB and Induction of Apoptosis by Tumor Necrosis Factor-α in the Mouse Uterine Epithelial WEG-1 Cell Line1
| Autor: | Ivo Vanderheyden, Stefan Cikos, René De Hertogh, Benjamin Picry, Sabine Cordi, S. Pampfer |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Ceramide medicine.medical_treatment Cell Biology General Medicine Biology chemistry.chemical_compound Endocrinology Cytokine Reproductive Medicine chemistry Apoptosis Cell culture Internal medicine medicine Cancer research Tumor necrosis factor alpha Signal transduction Protein kinase A |
| Zdroj: | Biology of Reproduction. 63:879-886 |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1095/biolreprod63.3.879 |
| Popis: | In order to better understand how tumor necrosis factor (TNF)-alpha may contribute to the local regulation of uterine cell death, cultures of mouse uterine epithelial WEG-1 cells were exposed to TNF-alpha and observed at different time intervals. Earliest decrease in cell viability was observed after 31 h of exposure to 50 ng/ml mouse TNF-alpha and was associated with the expression of several markers of apoptosis. Treatment with human TNF-alpha or addition of a neutralizing antibody against TNF-alpha receptor protein 80 to mouse TNF-alpha resulted in attenuated induction of apoptosis, suggesting that coengagement of the two TNF-alpha receptor types is required for maximal impact. Ceramide analogs failed to replicate the effect of TNF-alpha and the stress-activated protein kinase signaling pathway was not activated by the cytokine. Treatment with mouse TNF-alpha resulted in an increase in nuclear factor (NF)kappaB activity that receded after 24 h. The impact of human TNF-alpha on NFkappaB activation was more moderate. Addition of either one of three different inhibitors of NFkappaB (SN50, PDTC, and A771726) to mouse TNF-alpha sensitized WEG-1 cells to the toxicity of the cytokine. Our data suggest that WEG-1 cells initiate their response to TNF-alpha with an increase in NFkappaB activation that may have transiently biased these cells toward cell death resistance. |
| Databáze: | OpenAIRE |
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