NF-κ-B functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type

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Abstract

Recently NF-κ-B has been shown to have both proapoptotic and antiapoptotic functions. In T cell hybridomas, both T cell activators and glucocorticoids induce apoptosis. Here we show that blockade of NF-κB activity, using a dominant negative IκBα, has opposite effects on these two apoptotic signals. Treatment with PMA plus ionomycin (P/I) results in the upregulation of Fas Ligand (FasL) and induction of apoptosis. Inhibition of NF-κB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-κB as a proapoptotic factor in this context. Conversely inhibition of NF-κ-B confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-κB also functions as an antiapoptotic factor. We conclude that NF-κB is a context-dependent apoptosis regulator. Our data suggests that NF-κB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells.

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Lin, B., Williams-Skipp, C., Tao, Y., Schleicher, M. S., Cano, L. L., Duke, R. C., & Scheinman, R. I. (1999). NF-κ-B functions as both a proapoptotic and antiapoptotic regulatory factor within a single cell type. Cell Death and Differentiation, 6(6), 570–582. https://doi.org/10.1038/sj.cdd.4400528

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