抄録
Prostaglandin E2 (PGE2), the brain mediator of fever, is produced in brain endothelial cells through the actions of PGE2-synthesizing enzymes including cyclooxygenase-2 (COX-2) and microsomal-type PGE synthase (mPGES). However, the type of phospholipase A2 (PLA2) working in the upstream of COX-2 is unknown. We have previously shown a possible involvement of calcium-independent PLA2 (iPLA2) in brain PGE2 production during lipopolysaccharide (LPS)-induced fever, since systemic pretreatment of rats with an inhibitor of iPLA2, BEL, suppressed fever and brain PGE2 production. Here, we examined whether BEL directly acts on brain endothelial cells to suppress PGE2 production using an ex vivo preparation of brain blood vessels. PGE2 release from subarachnoidal blood vessels, which were isolated from LPS-injected rats and incubated ex vivo, was suppressed by BEL (10μM) added to the incubation medium. Unexpectedly, BEL also suppressed COX-2 expression in endothelial cells of isolated blood vessels. These results indicate that BEL directly acts on brain endothelial cells to suppress PGE2 production, and suggest that arachidonic acid produced through the BEL-sensitive pathway might not only be a substrate for COX-2 but also be involved in the induction of COX-2. Our findings support the idea that iPLA2 is working in the upstream of COX-2 in brain endothelial cells to produce PGE2 during LPS-induced fever. [J Physiol Sci. 2006;56 Suppl:S228]
