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 neurodegenerative processes including Alzheimer's disease. However, the mechanisms leading to increased IL-6 expression in the brain remain largely unknown. We have studied the effects of synthetic ceramides and sphingomyelinase as possible regulators of IL-6 gene expression in a human astrocytoma cell line. The synthetic ceramides C2- and C6-ceramide as well as the enzyme sphingomyelinase were able to induce IL-6 gene transcription and protein synthesis in a dose-dependent manner with maximal IL-6 mRNA levels being reached after 4 h of ceramide treatment. We propose that the sphingomyelin pathway is part of the signal transduction cascade leading to IL-6 gene expression in astrocytes, and that this pathway may be involved in IL-6-mediated neurodegenerative processes.
Fiebich
B L
BL
Psychiatrische Klinik, Universität Freiburg, Germany.
Lieb
K
K
Berger
M
M
Bauer
J
J
D001253:Astrocytes / Q000201:enzymology / Q000276:immunology; D001254:Astrocytoma / Q000473:pathology*; D002460:Cell Line / Q000276:immunology; D002518:Ceramides / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000494:pharmacology; D013109:Sphingomyelins / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D002518:Ceramides; D015850:Interleukin-6; D011506:Proteins; D012333:RNA, Messenger; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase