Effect of NF-κB activity on TNF-α–induced signaling.

TNF-α–induced signaling is modulated by the activity of NF-κB. (A) Cell viability (mean ± SD) was assayed by MTT in MM.1S cells treated with or without TNF-α (50 ng/mL), in the presence or absence of SN50 (10 μM) for 18 hours. Data shown (absorbance at 570 nm, mean ± SD) are representative of 3 experiments. In MM.1S cells pretreated with SN50, TNF-α induced apoptosis, rather than cell growth. (B) This was evidenced by cleavage and activation of caspase-8 and downstream caspase-3 and was associated with down-regulation of expression of the caspase-8 inhibitory proteins cIAP-1 and cIAP-2 In contrast, TNF-α alone up-regulated cIAP-1 and cIAP-2 expression. Moreover, TNF-α up-regulated adhesion molecule intercellular adhesion molecule–1 (ICAM-1) expression, and SN50 blocked this effect.