Prostaglandin E2 induces apoptosis in cultured rat microglia

Prostaglandin E-2 (PGE(2)) plays a critical role in the modulation of microglial function including migration and phagocytosis through EP2, which increases intracellular cyclic adenosine monophosphate (AMP) concentration. In the present study, we found that PGE(2) reduces cell viability in microglia. PGE(2) decreased 3-(4,5-dimethylthiazol-2-thiazoly1)-2,5-diphenyltetrazolium bromide (MTT) reduction and increased lactate dehydrogenase release, deoxyribonucleic acid fragmentation, and poly(ADP-ribose) polymerase cleavage after 24 h incubation, suggesting that PGE(2) induces apoptosis in these cells. An EP2 agonist, butaprost, and an EP4 agonist, PGE(1) alcohol, also induced apoptosis, while an EP1 agonist, 17-phenyl trinor PGE(2), or an EP3 agonist, sulprostone, at 10(-6) M did not. On the other hand, EP1-EP4 antagonists, SC-51322, AH6809, L-798106, or GW627368X, up to 10(-5) M did not affect the decrease in MTT reduction by PGE(2). Intracellular cyclic AMP accumulation was induced by butaprost, but not 17-phenyl trinor PGE(2), sulprostone, or PGE(1) alcohol at 10(-6) M. Additionally, we previously reported that PGE(2)-induced intracellular cyclic AMP accumulation was reversed by AH6809. Besides EP receptors, one of other targets was thought to be prostaglandin transporter, but its inhibitors, bromocresol green or U-46619 up to 10(-5) M did not affect the decrease in MTT reduction by PGE(2). These results suggest that PGE(2) induces apoptosis in microglia independent of intracellular cyclic AMP concentration, and there are different mechanisms between PGE(2)-induced apoptosis and the modulation of microglial function. (C) 2014 Elsevier B.V. All rights reserved.