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

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)E- and PGI-mediated tumor necrosis factor α (TNF-α) regulation. Specifically, PGE accumulation in astrocyte activated the p38 and JNK/c-Jun signaling pathways phosphorylation, resulting in TNF-α expression. In contrast, the administration of PGI attenuated the effects of PGE 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 Aβ oligomers but also Aβ fibrils have the ability to involve in mediating the antagonistic effects of PGE and PGI on regulating the expression of TNF-α 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) in β-amyloid plaques (APs), which contribute to the cognitive decline of AD.