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

Abstract

Recently NF-kB 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-kB activity, using a dominant negative IkBa, 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-kB activity inhibits the P/I mediated induction of FasL mRNA and decreases the level of apoptosis in these cultures, thus establishing NF-kB as a proapoptotic factor in this context. Conversely, inhibition of NF-kB confers a tenfold increase in glucocorticoid mediated apoptosis, establishing that NF-kB also functions as an antiapoptotic factor. We conclude that NF-kB is a context-dependent apoptosis regulator. Our data suggests that NF-kB may function as an antiapoptotic factor in thymocytes while functioning as a proapoptotic factor in mature peripheral T cells.

To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis

“…In this context, NF-kB triggered the Fas-death cascade by directly activating the expression of Fas ligand (FasL) ( Duyao et al (1990), La Rosa et al (1994) et al, 1999; Lin et al, 1999;Zheng et al, 2001). The expression of a dominant IkB molecule (IkBaM) inhibited both FasL expression and apoptosis.…”

TNF combined with IFN-α accelerates NF-κB-mediated apoptosis through enhancement of Fas expression in colon cancer cells

“…31 Another report showed that activated NF-kB exhibited opposite functions following induction by different treatments in a single cell line; NF-kB activation induced by combined treatment with PMA and ionomycin was proapoptotic in a T-cell hybridoma cell line, whereas glucocorticoid-induced NF-kB was antiapoptotic in the same cells. 35 TNF/IFN-a induced a cytotoxic response in certain tumors, [18][19][20] and also had crosstalk interactions in immune responses. 36 We therefore investigated whether NF-kB activation induced by TNF/IFN-a, had an antiapoptotic or proapoptotic effect.…”

Osmotic stress sensitizes naturally resistant cells to TNF-α-induced apoptosis

“…19,20 Interestingly, NF-kB can either induce or repress apoptosis in CD4 + CD8 + thymocytes, depending upon the nature of the activator. 21 In addition, its role in apoptosis may be dependent of the cell type, probably due to cross talk with other signals. The precise molecular mechanisms that determine the switch from an anti-to a pro-apoptotic role have not been clearly defined.…”