title: Curcumin Ameliorates the Reduction Effect of PGE2 on Fibrillar β-Amyloid Peptide (1-42)-Induced Microglial Phagocytosis through the Inhibition of EP2-PKA Signaling in N9 Microglial Cells.
abstract: Inflammatory activation of microglia and β amyloid (Aβ) deposition are considered to work both independently and synergistically to contribute to the increased risk of Alzheimer's disease (AD). Recent studies indicate that long-term use of phenolic compounds provides protection against AD, primarily due to their anti-inflammatory actions. We previously suggested that phenolic compound curcumin ameliorated phagocytosis possibly through its anti-inflammatory effects rather than direct regulation of phagocytic function in electromagnetic field-exposed N9 microglial cells (N9 cells). Here, we explored the prostaglandin-E2 (PGE2)-related signaling pathway that involved in curcumin-mediated phagocytosis in fibrillar β-amyloid peptide (1-42) (fAβ42)-stimulated N9 cells. Treatment with fAβ42 increased phagocytosis of fluorescent-labeled latex beads in N9 cells. This increase was attenuated in a dose-dependent manner by endogenous and exogenous PGE2, as well as a selective EP2 or protein kinase A (PKA) agonist, but not by an EP4 agonist. We also found that an antagonist of EP2, but not EP4, abolished the reduction effect of PGE2 on fAβ42-induced microglial phagocytosis. Additionally, the increased expression of endogenous PGE2, EP2, and cyclic adenosine monophosphate (AMP), and activation of vasodilator-stimulated phosphoprotein, cyclic AMP responsive element-binding protein, and PKA were depressed by curcumin administration. This reduction led to the amelioration of the phagocytic abilities of PGE2-stimulated N9 cells. Taken together, these data suggested that curcumin restored the attenuating effect of PGE2 on fAβ42-induced microglial phagocytosis via a signaling mechanism involving EP2 and PKA. Moreover, due to its immune modulatory effects, curcumin may be a promising pharmacological candidate for neurodegenerative diseases.
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Gen-Lin
authors.initials: GL
authors.lastname: He
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Shen
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Tropic Hygiene, Institute of Tropical Medicine, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Xue-Sen
authors.initials: XS
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000276:immunology; D015232:Dinoprostone / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D010587:Phagocytosis / Q000187:drug effects*; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000276:immunology; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D010446:Peptide Fragments; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C075222:amyloid beta-protein (1-42); D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003474:Curcumin; D015232:Dinoprostone
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