ACTIVATION OF NEUTRAL SPHINGOMYELINASE BY IL-1β REQUIRES THE TYPE 1 INTERLEUKIN 1 RECEPTOR

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2000-03, Vol.12 (3), p.229-232
• Main Authors: Nalivaeva, Natalia N., Rybakina, Elena G., Yu. Pivanovich, Irina, Kozinets, Irina A., Shanin, Sergei N., Bartfai, Tamas
• Format: Article
• Language: English
• Subjects: interleukin 1/interleukin 1 receptor antagonist/interleukin 1 receptor type 1/neutral sphingomyelinase/knock-out mice
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1999.0547

The cytokine interleukin 1β (IL-1β) plays an important role in host defence reactions and neuro-immune interactions but it is still not clear which of the two interleukin 1 receptor subtypes is coupled to activation of neutral sphingomyelinase (nSMase) by IL-1β. To investigate involvement of neutral sphingomyelinase (nSMase) in central IL-1β effects we used P2fractions of brain cerebral cortex from wild-type mice and mice deficient in the type 1 IL-1 receptor. IL-1β (human, recombinant) was shown to activate, in a dose-dependent manner, nSMase in the P2brain fraction of the wild-type mice while in the knock-out mice the stimulatory effect of IL-1β on nSMase was absent. In the presence of an IL-1 receptor antagonist (IL-1ra), IL-1β did not activate nSMase either in the cortex of wild-type or knock-out mice. These data suggest that nSMase, a key enzyme of the sphingomyelin signal transduction pathway, might be involved in IL-1β signalling in the brain and that activation of the enzyme requires the IL-1 receptor type 1.