• Takayuki Nagano, Shinya H Kimura, and Motohiko Takemura.
• Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
• Brain Res. 2010 Apr 6; 1323: 11-7.

AbstractTreatment with amyloid beta(1-42) (Abeta(1-42)) at 1microM for 60min increased phagocytosis of latex beads by cultured rat microglia. This increase was reduced dose-dependently by prostaglandin E(2) (PGE(2)), but PGD(2), PGF(2alpha), iloprost, or U-46619 had no effects. PGE(2) also reduced the phagocytosis of fluorescent-labeled Abeta(1-42). Abeta(1-42)-induced phagocytosis was reduced by butaprost but not by 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol. The reduction effect of PGE(2) on phagocytosis was reversed by AH6809, an E-prostanoid receptor 2 (EP2) antagonist, which inhibited cyclic adenosine monophosphate (AMP) accumulation induced by PGE(2). Butaprost, but not 17-phenyl trinor PGE(2), sulprostone, or PGE(1) 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, Abeta(1-42)-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. Abeta(1-42) or PGE(2) had little effect on the expression levels of COX-1 or COX-2. These results indicate that Abeta(1-42)-induced microglial phagocytosis is reduced by PGE(2) through EP2.Copyright 2010 Elsevier B.V. All rights reserved.

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