Acid sphingomyelinase is not essential for the IL-1 and tumor necrosis factor receptor signaling pathway leading to NFkB activation.
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 transduction, we examined the ability of Niemann-Pick disease (NPD) type A fibroblasts, which are deficient in acid SMase, to induce IL-8 gene expression through activating NFkB. Unexpectedly, IL-1 alpha and TNF-alpha efficiently induced IL-8 production and IL-8 mRNA in NPD type A fibroblasts as in normal fibroblasts. Furthermore, activation of NFkB was also induced in NPD type A fibroblasts in response to IL-1 alpha and TNF-alpha 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.
Kuno
K
K
Department of Pharmacology, Kanazawa University, Japan.
Sukegawa
K
K
Ishikawa
Y
Y
Orii
T
T
Matsushima
K
K
D001483:Base Sequence; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009542:Niemann-Pick Diseases / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013108:Sphingomyelin Phosphodiesterase / Q000502:physiology*
D007375:Interleukin-1; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D013108:Sphingomyelin Phosphodiesterase