Dataset Information

Prostaglandin I? Attenuates Prostaglandin E?-Stimulated Expression of Interferon ? in a ?-Amyloid Protein- and NF-?B-Dependent Mechanism.

ABSTRACT: Cyclooxygenase-2 (COX-2) has been recently identified as being involved in the pathogenesis of Alzheimer's disease (AD). However, the role of an important COX-2 metabolic product, prostaglandin (PG) I2, in AD development remains unknown. Using mouse-derived astrocytes as well as APP/PS1 transgenic mice as model systems, we firstly elucidated the mechanisms of interferon ? (IFN?) regulation by PGE2 and PGI2. Specifically, PGE2 accumulation in astrocytes activated the ERK1/2 and NF-?B signaling pathways by phosphorylation, which resulted in IFN? expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 on stimulating the production of IFN? via inhibiting the translocation of NF-?B from the cytosol to the nucleus. Due to these observations, we further studied these prostaglandins and found that both PGE2 and PGI2 increased A?1-42 levels. In detail, PGE2 induced IFN? expression in an A?1-42-dependent manner, whereas PGI2-induced A?1-42 production did not alleviate cells from IFN? inhibition by PGI2 treatment. More importantly, our data also revealed that not only A?1-42 oligomer but also fibrillar have the ability to induce the expression of IFN? via stimulation of NF-?B nuclear translocation in astrocytes of APP/PS1 mice. The production of IFN? finally accelerated the deposition of A?1-42 in ?-amyloid plaques.

SUBMITTER: Wang P

PROVIDER: S-EPMC4751455 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Prostaglandin I₂ Attenuates Prostaglandin E₂-Stimulated Expression of Interferon γ in a β-Amyloid Protein- and NF-κB-Dependent Mechanism.

Wang Pu P Guan Pei-Pei PP Yu Xin X Zhang Li-Chao LC Su Ya-Nan YN Wang Zhan-You ZY

Scientific reports 20160212

Cyclooxygenase-2 (COX-2) has been recently identified as being involved in the pathogenesis of Alzheimer's disease (AD). However, the role of an important COX-2 metabolic product, prostaglandin (PG) I2, in AD development remains unknown. Using mouse-derived astrocytes as well as APP/PS1 transgenic mice as model systems, we firstly elucidated the mechanisms of interferon γ (IFNγ) regulation by PGE2 and PGI2. Specifically, PGE2 accumulation in astrocytes activated the ERK1/2 and NF-κB signaling pa ...[more]

PMID: 26869183

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Dataset Information

Prostaglandin I? Attenuates Prostaglandin E?-Stimulated Expression of Interferon ? in a ?-Amyloid Protein- and NF-?B-Dependent Mechanism.

Publications

Prostaglandin I₂ Attenuates Prostaglandin E₂-Stimulated Expression of Interferon γ in a β-Amyloid Protein- and NF-κB-Dependent Mechanism.

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