TY - JOUR
T1 - RSV-induced prostaglandin E2 production occurs via cPLA2 activation
T2 - Role in viral replication
AU - Liu, Tianshuang
AU - Zaman, Wahiduz
AU - Kaphalia, Bhupendra S.
AU - Ansari, G. A.Shakeel
AU - Garofalo, Roberto P.
AU - Casola, Antonella
N1 - Funding Information:
This work was supported in part by grant number ES06676 from the National Institute of Environmental Health Sciences, a grant from the John Sealy Endowment Fund, UTMB (A.C.), a Beginning Grant-In-Aid from the American Heart Association, Texas Affiliate (A.C.). We thank Todd Elliott for his technical support.
PY - 2005/12/5
Y1 - 2005/12/5
N2 - 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 epithelial 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 (cPLA2) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA2 significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA2 in viral-induced PG production. Blocking PG secretion, through cPLA2 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.
AB - 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 epithelial 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 (cPLA2) enzymatic activity and its membrane translocation. Specific inhibitors of cPLA2 significantly block RSV-induced PGE2 secretion, indicating a key role of cPLA2 in viral-induced PG production. Blocking PG secretion, through cPLA2 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.
KW - Airway epithelial cells
KW - Inflammation
KW - Prostaglandin
KW - RSV
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U2 - 10.1016/j.virol.2005.08.012
DO - 10.1016/j.virol.2005.08.012
M3 - Article
C2 - 16153673
AN - SCOPUS:27644566970
SN - 0042-6822
VL - 343
SP - 12
EP - 24
JO - Virology
JF - Virology
IS - 1
ER -