Prostaglandin E-2 synthesis and secretion: The role of PGE(2) synthases

Prostaglandin E-2 (PGE(2)) is a principal mediator of inflammation in diseases such as rheumatoid arthritis and osteciarthritis. Nonsteroidal anti-inflammatory medications (NSAIDs) and selective cyclooxygenase-2 (COX-2) inhibitors reduce PGE(2) production to diminish the inflammation seen in these diseases, but have toxicities that may include both gastrointestinal bleeding and prothrombotic tendencies. In cells, arachiclonic acid is transformed into PGE(2) via cyclooxygenase (COX) enzymes and terminal prostaglandin E synthases (PGES). Accumulating data suggest that the interaction of various enzymes in the PGE(2) synthetic pathway is complex and tightly regulated. In this review, we summarize the synthesis and secretion of PGE(2). In particular, we focus on the three isoforms of the terminal PGES, and discuss the potential of targeting PGES as a more precise strategy for inhibiting PGE(2) production. (c) 2006 Elsevier Inc. All rights reserved.