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

We recently demonstrated that the are-inflammatory cytokine, interleukin 1 beta (IL-1 beta) elevates intracellular free Ca2+ levels ([Ca2+](i)) in rat cortical synaptosomes in a manner involving activation of the IL-1 recepto r and stimulation of p42 mitogen-activated protein (MAP) kinase, We now rep ort that the effects of IL-1 beta on [Ca2+](i) are mimicked by the sphingol ipid metabolite ceramide, In cortical synaptosomes ceramide elevates [Ca2+] (i) in a p42 MAP kinase-dependent manner, and we conclude that the effects of IL-1 beta on Ca2+ homeostasis involve ceramide as an upstream component of the p42 MAP kinase pathway. (C) 2000 Academic Press.