Acid sphingomyelinase is not essential for the IL-1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation

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Abstract
A recent report has suggested that tumor necrosis factor (TNF) utilizes acid sphingomyelinase (SMase) pathway to activate NFkB (Schutze et al. 1992. Cell 71:765). To directly investigate the role of acid SMase in IL-1 and TNF receptor-mediated signal transductlon, we examined the ability of Niemann-Pick disease (NPD) type A fibrobiasts, which are deficient in acid SMase, to induce IL-8 gene expression through activating NFkB. Unexpectedly, IL-1α and TNF-8 efficiently induced IL-8 production and IL-8 mRNA in NPD type A flbrobiasts as in normal fibrobiasts. Furthermore, activation of NFkB was also induced in NPD type A fibroblasts in response to IL-1 a and TNF-α stimulation to a similar extent as in normal fibroblasts. These results provide evidence that acid SMase is not essential in IL-1 and TNF receptor signaling leading to NFkB activation as well as the cytokine gene activation which is regulated by NFkB.

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