title: Prostaglandin I₂ Attenuates Prostaglandin E₂-Stimulated Expression of Interferon γ in a β-Amyloid Protein- and NF-κB-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 γ (IFNγ) regulation by PGE2 and PGI2. Specifically, PGE2 accumulation in astrocytes activated the ERK1/2 and NF-κB signaling pathways by phosphorylation, which resulted in IFNγ expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 on stimulating the production of IFNγ via inhibiting the translocation of NF-κB from the cytosol to the nucleus. Due to these observations, we further studied these prostaglandins and found that both PGE2 and PGI2 increased Aβ1-42 levels. In detail, PGE2 induced IFNγ expression in an Aβ1-42-dependent manner, whereas PGI2-induced Aβ1-42 production did not alleviate cells from IFNγ inhibition by PGI2 treatment. More importantly, our data also revealed that not only Aβ1-42 oligomer but also fibrillar have the ability to induce the expression of IFNγ via stimulation of NF-κB nuclear translocation in astrocytes of APP/PS1 mice. The production of IFNγ finally accelerated the deposition of Aβ1-42 in β-amyloid plaques.
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Pu
authors: P
authors: Wang
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Pei-Pei
authors: PP
authors: Guan
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Xin
authors: X
authors: Yu
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Li-Chao
authors: LC
authors: Zhang
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Ya-Nan
authors: YN
authors: Su
authors: College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China.
authors: Zhan-You
authors: ZY
authors: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D009578:Nitrobenzenes / Q000494:pharmacology; D053764:Presenilin-1 / Q000378:metabolism; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D016328:NF-kappa B; D009578:Nitrobenzenes; D053764:Presenilin-1; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007371:Interferon-gamma; D011464:Epoprostenol; D015232:Dinoprostone