Abstract
Prostanoids including prostaglandins (PGs) and thromboxanes (TX) are a group of lipid mediators produced from membrane lipid in response to various stimuli. While the roles of prostanoids in acute inflammatory responses have been well defined, it is generally believed that prostanoids don't play significant roles in the immune response. This is partly because non-steroidal anti-inflammatory drugs that inhibit all prostanoid synthesis have little effects on immune processes in vivo. Prostanoids exert their actions by acting on a family of G-protein-coupled receptors, including PGD receptor, EP1, EP2, EP3 and EP4 subtypes of PGE receptor, PGF receptor, PGI receptor and TX receptor. We generated mice deficient in each of these prostanoid receptors, and examined their roles under various pathological conditions. These studies have revealed that prostanoids works at various levels of immune responses and exert many, often opposing, actions. For example, we found that PGE2-EP4 signaling facilitates migration and maturation of dendritic cells in contact hypersensitivity, while the same pathway suppresses T cell activation and proliferation in the gut of mice subjected to dextran sodium sulfate-induced colitis, a model of inflammatory bowel disease. These findings suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of certain immunological disorders.
