Prostaglandin E 2 regulates amyloid precursor protein expression via the EP2 receptor in cultured rat microglia

Abstract

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 PGE 2 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.