Prostaglandin E2 reduces amyloid β-induced phagocytosis in cultured rat microglia

Treatment with amyloid β1–42 (Aβ1–42) at 1 µM for 60 min increased phagocytosis of latex beads by cultured rat microglia. This increase was reduced dose-dependently by prostaglandin E2 (PGE2), but PGD2, PGF2α, iloprost, or U-46619 had no effects. PGE2 also reduced the phagocytosis of fluorescent-labeled Aβ1–42. Aβ1–42-induced phagocytosis was reduced by butaprost but not by 17-phenyl trinor PGE2, sulprostone, or PGE1 alcohol. The reduction effect of PGE2 on phagocytosis was reversed by AH6809, an E-prostanoid receptor 2 (EP2) antagonist, which inhibited cyclic adenosine monophosphate (AMP) accumulation induced by PGE2. Butaprost, but not 17-phenyl trinor PGE2, sulprostone, or PGE1 alcohol increased intracellular cyclic AMP accumulation. In western blotting analysis, EP2-like immunoreactivity was detected in the crude membrane fraction of microglia. On the other hand, Aβ1–42-induced phagocytosis was not affected by SC-560, a cyclooxygenase-1 (COX-1) inhibitor, NS-398, a COX-2 inhibitor, or ibuprofen, a non-specific COX inhibitor. Aβ1–42 or PGE2 had little effect on the expression levels of COX-1 or COX-2. These results indicate that Aβ1–42-induced microglial phagocytosis is reduced by PGE2 through EP2.