STIMULATION OF THE SPHINGOMYELIN PATHWAY INDUCES INTERLEUKIN-6 GENE-EXPRESSION IN HUMAN ASTROCYTOMA-CELLS

Interleukin-6 (IL-6) has previously been shown to participate in neuro degenerative processes including Alzheimer's disease. However, the mec hanisms leading to increased IL-6 expression in the brain remain large ly unknown. We have studied the effects of synthetic ceramides and sph ingomyelinase as possible regulators of IL-6 gene expression in a huma n astrocytoma cell line. The synthetic ceramides C-2- and C-6-ceramide as well as the enzyme sphingomyelinase were able to induce IL-6 gene transcription and protein synthesis in a dose-dependent manner with ma ximal IL-6 mRNA levels being reached after 4 h of ceramide treatment. We propose that the sphingomyelin pathway is part of the signal transd uction cascade leading to IL-6 gene expression in astrocytes, and that this pathway may be involved in IL-6-mediated neurodegenerative proce sses.