抄録
Prostaglandin E2 (PGE2), the brain mediator of fever, is thought to be produced in brain endothelial cells, as these cells express PGE2-synthesizing enzymes such as cyclooxygenase-2 (COX-2) and microsomal-type PGE synthase in response to pyrogen lipopolysaccharide (LPS). However, it is not directly demonstrated yet if these cells actually produce PGE2 in response to LPS, and which type of phospholipase A2 (PLA2) is working in the upstream of COX-2. To solve these issues, we here established an ex vivo model of PGE2 production in brain blood vessels. Subarachnoidal blood vessels together with arachnoidal membrane were isolated from the rat brain 4 hrs after intraperitoneal injection of either saline or LPS (400 mg/kg). The samples were incubated in HEPES-buffered Ringer solution for one hour at 37°C in the presence or the absence of various enzyme inhibitors, and concentrations of PGE2 in the incubation medium were measured using EIA. PGE2 production was significantly enhanced in blood vessels from LPS-treated rats compared to those from saline-treated ones. A COX-2 inhibitor added to the incubation medium significantly suppressed the PGE2 production. Since endothelial cells are the major COX-2 expressing cells there, these results directly indicate that brain endothelial cells enhance PGE2 production in response to peripheral LPS stimulus. This ex vivo model could be further useful to examine the type of PLA2 involved in PGE2 production during fever. [Jpn J Physiol 54 Suppl:S231 (2004)]
