RSV-induced prostaglandin E2 production occurs via cPLA2 activation:: Role in viral replication

Prostaglandins (PGs) are lipid mediators that participate in the regulation of immunological and inflammatory responses, and PG production can affect viral replication. In this study, we have investigated the mechanism of PGE2 production in airway epithelia] cells, following respiratory syncytial virus (RSV) infection, and its role in viral replication. We show that RSV infection strongly induces PGE2 secretion, in a time- and replication-dependent manner, through increased cyclooxygenase-2 (COX-2) expression, which occurs independently from viral or cellular protein synthesis. RSV infection induces arachidonic acid release through induction of cytoplasmic phospholipase A(2) (cPLA(2)) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA(2) significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA(2) in viral-induced PG production. Blocking PG secretion, through cPLA(2) or COX-2 inhibition, results in impairment of RSV replication and subsequent RSV-mediated epithelial cell responses, suggesting that inhibition of PG secretion could be beneficial in RSV infection by reducing proinflammatory mediator production. (C) 2005 Elsevier Inc. All rights reserved.