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lüll The IL-1 receptor signaling pathway Kuno K; Matsushima KJ Leukoc Biol 1994[Nov]; 56 (5): 542-7Interleukin-1 (IL-1) exerts pleiotropic effects on a variety of tissues through binding to its receptor. Two distinct types of receptors for IL-1 have been characterized in mouse and human. Most of the IL-1 signal has been shown to be transmitted through type I IL-1R (80 kDa) in T lymphocytes as well as B lymphocytes and monocytes. Type II receptor may act as a suppressor of IL-1 biological activities by competing in binding with type I receptors on the cell surface. Functional studies of the type I IL-1R demonstrated that the cytoplasmic segments, possessing a sequence similarity with the Drosophila Toll gene product or IL-6R beta chain, gp130, are important for transmitting activity that induces cytokine genes. In the past three years, several groups reported that IL-1 and tumor necrosis factor (TNF) rapidly induce sphingomyelin turnover in various types of cells, producing ceramide, which may act as a second messenger molecule in an intracellular signaling cascade. Activation of both acid and neutral sphingomyelinases (SMases) has been suggested, and Schutz et al. proposed that the phosphatidylcholine-phospholipase C/acid SMase pathway is involved in TNF-induced NF-kappa B activation. However, our recent study showed that the NF-kappa B activation is induced by IL-1/TNF in fibroblasts from patients with type A Niemann-Pick disease, with acid SMase deficiency. This finding implies that acid SMase activity is not essential for the activation of NF-kappa B by IL-1/TNF at least in fibroblasts. Other signaling pathways including neutral SMase and unidentified protein kinases may be important for NF-kappa B-mediated cytokine gene activation.|Amino Acid Sequence[MESH]|Cell Line[MESH]|Ceramides/metabolism[MESH]|Conserved Sequence[MESH]|Cyclic AMP-Dependent Protein Kinase Type II[MESH]|Cyclic AMP-Dependent Protein Kinases/metabolism[MESH]|Enzyme Activation[MESH]|Fibroblasts/metabolism[MESH]|Humans[MESH]|Interleukin-1/*metabolism[MESH]|Molecular Sequence Data[MESH]|NF-kappa B/metabolism[MESH]|Protein Kinase C/metabolism[MESH]|Reactive Oxygen Species/metabolism[MESH]|Receptors, Interleukin-1/chemistry/genetics/*physiology[MESH]|Receptors, Tumor Necrosis Factor/metabolism[MESH]|Signal Transduction/*physiology[MESH]|Sphingomyelin Phosphodiesterase/metabolism[MESH]|Sphingomyelins/metabolism[MESH]|Structure-Activity Relationship[MESH] |