ABSTRACT The ability of pro-inflammatory cytokines such as interleukin-1 (IL-1) to induce the major inflammatory mediator prostaglandin (PG) E 2 depends on the activation of two rate-limiting enzymes, phospholipase A 2 (PLA 2 ) and cyclooxygenase 2 (COX-2). PLA 2 acts to generate arachidonic acid, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to PGE 2 production. However, less is known about the mechanisms that coordinate the regulation of these two enzymes. We have provided prior evidence that sphingosine kinase 1 and its bioactive lipid product sphingosine-1-phosphate (S1P) mediate the effects of cytokines on COX-2 induction, whereas ceramide kinase and its distinct product, ceramide-1-phosphate (C1P), are required for the activation and translocation of cPLA 2 (FASE
