Activation of nuclear factor kappaB and induction of apoptosis by tumor necrosis factor-alpha in the mouse uterine epithelial WEG-1 cell line.
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.
Pampfer
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S
OBST 5330 Research Unit, Université Catholique de Louvain Medical School, 1200 Brussels, Belgium. pampfer@obst.ucl.ac.be
Cordi
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S
Cikos
S
S
Picry
B
B
Vanderheyden
I
I
Hertogh
R D
RD
D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002518:Ceramides / Q000494:pharmacology; D003437:Crotonates; D053938:DNA Fragmentation; D005260:Female; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles; D010455:Peptides / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction; D013859:Thiocarbamates / Q000494:pharmacology; D014052:Toluidines; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014599:Uterus / Q000166:cytology* / Q000378:metabolism*
D000814:Aniline Compounds; D002518:Ceramides; D003437:Crotonates; D006885:Hydroxybutyrates; D016328:NF-kappa B; D009570:Nitriles; D010455:Peptides; C118258:SN50 peptide; D013859:Thiocarbamates; D014052:Toluidines; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; C527525:teriflunomide; D011392:Proline