Activation of neutral sphingomyelinase by IL-1beta requires the type 1 interleukin 1 receptor.
The cytokine interleukin 1beta (IL-1beta) 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-1beta. To investigate involvement of neutral sphingomyelinase (nSMase) in central IL-1beta effects we used P(2)fractions of brain cerebral cortex from wild-type mice and mice deficient in the type 1 IL-1 receptor. IL-1beta (human, recombinant) was shown to activate, in a dose-dependent manner, nSMase in the P(2)brain fraction of the wild-type mice while in the knock-out mice the stimulatory effect of IL-1beta on nSMase was absent. In the presence of an IL-1 receptor antagonist (IL-1ra), IL-1beta 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-1beta signalling in the brain and that activation of the enzyme requires the IL-1 receptor type 1.
Nalivaeva
N N
NN
Department of Comparative Neurochemistry, Institute of Evolutionary Biochemistry and Physiology, St. Petersburg, Russia. n.n.nalivaeva@leeds.ac.uk
Rybakina
E G
EG
Pivanovich IYu
Kozinets
I A
IA
Shanin
S N
SN
Bartfai
T
T
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004789:Enzyme Activation; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D053573:Receptors, Interleukin-1 Type I; D015398:Signal Transduction; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*
D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D013108:Sphingomyelin Phosphodiesterase