Prostaglandin E2 reduces amyloid beta-induced phagocytosis in cultured rat microglia.
Treatment 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.
Nagano
Takayuki
T
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Kimura
Shinya H
SH
Takemura
Motohiko
M
D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D051381:Rats; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D058307:Receptors, Prostaglandin E, EP2 Subtype; C075222:amyloid beta-protein (1-42); D000242:Cyclic AMP; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone