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Biology of Reproduction 63, 879-886 (2000)
© 2000 Society for the Study of Reproduction, Inc.


Regular Article

Activation of Nuclear Factor {kappa}B and Induction of Apoptosis by Tumor Necrosis Factor-{alpha} in the Mouse Uterine Epithelial WEG-1 Cell Line1

Serge Pampfer2,a, Sabine Cordia, Stefan Cikos3,a, Benjamin Picrya, Ivo Vanderheydena, and René De Hertogha

a OBST 5330 Research Unit, Université Catholique de Louvain Medical School, 1200 Brussels, Belgium

ABSTRACT

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){kappa}B activity that receded after 24 h. The impact of human TNF-{alpha} on NF{kappa}B activation was more moderate. Addition of either one of three different inhibitors of NF{kappa}B (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 NF{kappa}B activation that may have transiently biased these cells toward cell death resistance.

FOOTNOTES

First decision: 20 March 2000.

1 Research supported by the Fonds de la Recherche Scientifique Médicale (convention 3.4527.99), the Fonds Suzanne and Jean Pirart de l'Association Belge du Diabète, and the Commission des Relations Internationales de l'Université Catholique de Louvain (grant CGLSF524). S.P. is a Chercheur Qualifié with the Fonds National de la Recherche Scientifique.

2 Correspondence: Serge Pampfer, OBST 5330 Research Unit, Université Catholique de Louvain Medical School, 53 Avenue Mounier, 1200 Brussels, Belgium. FAX: 32 2 7645396; pampfer{at}obst.ucl.ac.be

3 Current address: Institute of Animal Physiology, Slovak Academy of Sciences, Kosice, Slovakia.




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