Tumor necrosis factor α activates NF-κB in acid sphingomyelinase- deficient mouse embryonic fibroblasts

Abstract

Tumor necrosis factor α (TNF-α) is one of the most potent inducer of the nuclear transcription factor κB (NF-κB). Activation of NF-κB is initiated by phosphorylation of the inhibitory subunit of the IκB-α-NF-κB complex. This leads to the dissociation of the complex and degradation of IκB-α. NF-κB is translocated into the nucleus. The sphingomyelin pathway is thought to mediate the TNF-α-induced activation of NF-κB by its second messenger ceramide. We have used the recently established acid sphingomyelinase-deficient mouse line (asmase(-/-) mice) to evaluate the role of acid sphingomyelinase in the TNF-α-induced signal transduction pathway. Here we present experimental evidence that acid sphingomyelinase is not involved in the TNF-α-induced activation of NF-κB. TNF-α treatment induced the dissociation and degradation of IκB-α and the nuclear translocation of NF-κB in embryonic fibroblasts derived from asmase(-/-) and wild type mice indiscriminately.