Interleukin-1β induced cyclooxygenase 2 expression and prostaglandin E2 secretion by human neuroblastoma cells:: implications for Alzheimer's disease

Non-steroidal anti-inflammatory drugs (NSAIDs) may decrease the risk of developing Alzheimer's disease (AD). Cyclooxygenase 2 (COX-2), one of the targets of NSAIDs, is increasingly expressed in neuronal cells in AD brain. In this study, of the cytokines that are found at increased levels in AD brain (interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor (TNF)alpha), IL-1 beta was found to induce COX-2 immunoreactivity and prostaglandin (PG) E2 secretion by human neuroblastoma cell line SK-N-SH. COX inhibitors indomethacin and BF389, as well as the glucocorticoid dexamethasone (DEX) and pyrrolidinedithiocarbamate, which is an inhibitor of nuclear factor kappaB as well as a potent antioxidant, inhibited IL-1 beta induced PGE2 secretion. In addition, DEX reduced the IL-I beta induced COX-2 immunoreactivity in the same concentration as wherein it inhibited PGE2 secretion. Palmitoyl trifluormethyl ketone, an inhibitor of Ca2+ independent phospholipase A(2) (iPLA(2)) and a less potent inhibitor of cytosolic PLA(2), dose-dependently reduced the IL-1 beta induced PGE2 secretion. This suggests that the IL-1 beta induced PGE2 secretion may depend on the availability of arachidonic acid. Although the physiological role of neuronal COX-2 still remains unclear, we suggest an interplay between glial derived IL-1 and neuronal upregulation of COX-2 expression in chronic neurodegenerative diseases, such as AD. (C) 2001 Elsevier Science Inc. All rights reserved.