Activation of the Sphingomyelin Signaling Pathway in Intact EL4 Cells and in a Cell-Free System By IL-1β

作者：Shalini Mathias, Anas Younes, Chu-Cheng Kan, Irene Orlow, Cecil K. Joseph, Richard Kolesnick · 发表于：Science · 年份：1993 · DOI：10.1126/science.8424175 · 被引用次数：437 · 研究领域：Sphingolipid Metabolism and Signaling、Phagocytosis and Immune Regulation、Erythrocyte Function and Pathophysiology

The mechanism of interleukin-1 (IL-1) signaling is unknown. Tumor necrosis factor-alpha uses a signal transduction pathway that involves sphingomyelin hydrolysis to ceramide and stimulation of a ceramide-activated protein kinase. In intact EL4 thymoma cells, IL-1 beta similarly stimulated a rapid decrease of sphingomyelin and an elevation of ceramide, and enhanced ceramide-activated protein kinase activity. This cascade was also activated by IL-1 beta in a cell-free system, demonstrating tight coupling to the receptor. Exogenous sphingomyelinase, but not phospholipases A2, C, or D, in combination with phorbol ester replaced IL-1 beta to stimulate IL-2 secretion. Thus, IL-1 beta signals through the sphingomyelin pathway.