Low Temperatures and Hypertonicity Do Not Block Cytokine-induced Stimulation of the Sphingomyelin Pathway but Inhibit Nuclear Factor-κB Activation

摘要: In order to better understand the significance of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β)-receptor internalization in sphingomyelin pathway signal transduction, we investigated receptor signaling under conditions which is blocked. We demonstrate that human recombinant TNF-α IL-1β both induced phosphatidylcholine hydrolysis at either 4, 14, or 37°C skin fibroblasts U937 monocytic cells. Cytokine-induced degradation also occurred when endocytosis was inhibited by incubating cells hypertonic medium. While not required for production ceramide, activation transcription factor NF-κB strongly reduced were stimulated with TNF low temperature Under these conditions, cell-permeant C2-ceramide (N-acetylsphingosine), exogenous sphingomyelinase phorbol myristate acetate inhibited. These results suggest hypertonicity, two inhibitors internalization: (i) do affect TNF-α- IL-1β-induced hydrolysis, but (ii) inhibit a step distal ceramide intracellular leading activation.