Prostaglandin E2 regulates amyloid precursor protein expression via the EP2 receptor in cultured rat microglia

We investigated the effects of prostaglandin E-2 (PGE(2)) on amyloid precursor protein (APP) expression in cultured rat microglia. PGE(2) treatment significantly increased the expression of APP holoprotein and was associated with an elevation in cyclic AMP (cAMP). Direct activation of adenylate cyclase with forskolin also increased APP expression. Co-treatment of microglia with PGE(2) and the PKA inhibitor H-89 suppressed the overexpression of APP caused by PGE(2) alone. The prostaglandin EP2 receptor is known to be positively coupled to cAMP production. Stimulation of the EP2 receptor with butaprost increased APP holoprotein, whereas co-incubation of the cells with PGE2 and the EP2 receptor antagonist AH-6809 blocked the effect of PGE(2) on APP expression. These data suggest that PGE(2) is able to regulate the expression of APP, and that this effect may be mediated by the EP2 receptor and the cAMP signaling cascade. (C) 2004 Elsevier Ireland Ltd. All rights reserved.