Research Papers: Gerotarget (Focus on Aging):

Prostaglandin I2 is responsible for ameliorating prostaglandin E2 stress in stimulating the expression of tumor necrosis factor α in a β-amyloid protein -dependent mechanism

Shao-Qin Zheng, Zi-Yi Gong, Chen-Di Lu and Pu Wang _

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Oncotarget. 2017; 8:102801-102819. https://doi.org/10.18632/oncotarget.18462

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Shao-Qin Zheng1, Zi-Yi Gong1, Chen-Di Lu1 and Pu Wang1

1 The College of Life and Health Sciences, Northeastern University, Shenyang, P. R. China

Correspondence to:

Pu Wang, email:

Keywords: prostaglandin I2, prostaglandin E2, tumour necrosis factor α, β-amyloid protein, p38, Gerotarget

Received: March 04, 2017 Accepted: May 08, 2017 Published: June 13, 2017


Cyclooxygenase-2 (COX-2) has been found to be induced during the early stage of Alzheimer’s disease (AD). Using mouse-derived astrocyte and APP/PS1 transgenic (Tg) mice as model systems, we firstly elucidated the mechanisms underlying COX-2 metabolic production including prostaglandin (PG)E2- and PGI2-mediated tumor necrosis factor α (TNF-α) regulation. Specifically, PGE2 accumulation in astrocyte activated the p38 and JNK/c-Jun signaling pathways via phosphorylation, resulting in TNF-α expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 in stimulating the production of TNF-α by inhibiting the activity of TNF-α promoter and the binding activity of AP1 on the promoter of TNF-α. Moreover, our data also showed that not only Aβ1-42 oligomers but also Aβ1-42 fibrils have the ability to involve in mediating the antagonistic effects of PGE2 and PGI2 on regulating the expression of TNF-α via a p38- and JNK/c-Jun-dependent, AP1-transactivating mechanism. Reciprocally, the production of TNF-α finally accelerated the deposition of β-amyloid protein (Aβ)1-42 in β-amyloid plaques (APs), which contribute to the cognitive decline of AD.

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