Roles of prostaglandin D_2 and prostaglandin E_2 in allergic reactions : pro-allergic and anti-allergic modulating pathways
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Prostaglandin(PG) D<SUB>2</SUB> and PGE<SUB>2</SUB> are major cyclooxygenase metabolites of arachidonic acid produced during allergic reactions including asthma. However, the role of PGD<SUB>2</SUB> and PGE<SUB>2</SUB> in allergic inflammation has long been ambiguous. This is partly because non-steroidal anti-inflammatory drugs that inhibit prostanoid synthesis are generally ineffective in allergic disorders. Both PGs exert their actions by acting on G-proteincoupled receptors; PGD<SUB>2</SUB> acts at the PGD receptor(DP), PGE<SUB>2</SUB> acts at four subtypes of PGE receptor, EP1 to EP4. To dissect the roles of PGD<SUB>2</SUB>-DP pathway and each PGE<SUB>2</SUB>-EP pathway in allergic reactions, we subject mice deficient in DP, EP1, EP2, EP3 and EP4 receptor individually to ovalbumin-induced allergic asthma as a model of type I allergy. These studies have revealed that there are opposing actions between two prostanoid pathways in allergic reactions; PGD<SUB>2</SUB>-DP pathway and PGE<SUB>2</SUB>-EP3 pathway. We found that the PGD<SUB>2</SUB> is an important mediator of allergic responses and that PGE<SUB>2</SUB>-EP3 signaling negatively regulates progression of allergic inflammation. This review focuses on the opposite roles of these prostanoid pathways in allergic reactions obtained by our studies and other studies. These findings suggest that selective manipulation of the prostanoid receptors may be beneficial in treatment of allergic diseases, such as bronchial asthma, allergic rhinitis and conjunctivitis.
Ensho 26(1), 29-34, 2006-01-25
The Japanese Society of Inflammation and Regeneration