The role of ceramide in the modulation of intracellular Ca2+ levels by interleukin 1 beta in rat cortical synaptosomes

We recently demonstrated that the pro-inflammatory cytokine, interleukin 1beta (IL-1beta) elevates intracellular free Ca2+ levels (Ca2+]i) in rat cortical synaptosomes in a manner involving activation of the IL-1 receptor and stimulation of p42 mitogen-activated protein (MAP) kinase. We now report that the effects of IL-1beta on Ca2+]i are mimicked by the sphingolipid metabolite ceramide. In cortical synaptosomes ceramide elevates Ca2+]i in a p42 MAP kinase-dependent manner, and we conclude that the effects of IL-1beta on Ca2+ homeostasis involve ceramide as an upstream component of the p42 MAP kinase pathway.