Interleukin-1 protects transformed keratinocytes from tumor necrosis factor-related apoptosis-inducing ligand- and CD95-induced apoptosis but not from ultraviolet radiation-induced apoptosis

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a new memb er of the tumor necrosis factor (TNF) family, induces apoptosis primarily o f transformed cells. Interleukin-1 was previously found to protect the kera tinocyte cell line KB hom TRAIL-induced apoptosis, thus we studied whether interleukin-1 also protects from other apoptotic stimuli (ultraviolet radia tion (UV), CD95-ligand). Interleukin-1 rescued KB cells from TRAIL- and CD9 5-induced apoptosis, which was critically dependent on nuclear factor kappa B, because cells transfected with a super-repressor form of the nuclear fa ctor KB inhibitor I kappa B were less protected. in contrast, UV-mediated a poptosis was not only not prevented by interleukin-1 but even enhanced. Thi s opposite effect of interleukin-1 was also observed for the expression of the inhibitor of apoptosis proteins (IAP). Whereas TRAIL- and CD95-mediated suppression of LAP expression was partially reversed by interleukin-1, UV- mediated down-regulation of IAPs was not reversed but even further enhanced . Increased apoptosis induced by interleukin-1 plus UV was accompanied by e xcessive TNF alpha release, implying that enhanced cytotoxicity is due to t he additive effect of these two apoptotic stimuli. Accordingly, enhanced ap optosis was reduced by blocking the TNF receptor-1. The opposite effects of interleukin-1 indicate that different mechanisms are involved in UV-induce d apoptosis compared with CD95- and TRAIL-mediated apoptosis. Furthermore, the data suggest that whether a signal acts in an antiapoptotic way or not does not only depend on the signal itself but also on the stimulus causing apoptosis.