Role of mitogen-activated protein kinases in influenza virus induction of prostaglandin E2 from arachidonic acid in bronchial epithelial cells

Background Influenza virus (IV) infection causes airway inflammation; however, it has not been determined whether IV infection could catabolize arachidonic acid cascade in airway epithelial cells. In addition, the responsible intracellular signalling molecules that catabolize arachidonic acid cascade have not been determined. Objective In the present study, to clarify these issues, we examined the cyclooxygenase (COX) expression, cytosolic phospholipase A(2) (cPLA(2)) phosphorylation and prostaglandin E-2 (PGE(2)) release in human bronchial epithelial cells (BEC) upon IV infection, and the role of mitogen-activated protein kinase (MAPK) including extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun-NH2-terminal kinase (JNK) in catabolizing arachidonic acid cascade in BEC. Methods COX-2 expression, phosphorylation of cPLA(2) and phosphorylation of ERK, JNK and p38 MAPK were determined by Western blot. The concentrations of PGE(2) were determined by ELISA. PD 98059 as a specific inhibitor of MAPK kinase-1 (MEK-1), an up-stream kinase of ERK, SB 203580 as a specific inhibitor of p38 MAPK and CEP-11004 as a specific inhibitor of JNK cascade were used to investigate the role of ERK, p38 MAPK and JNK in catabolizing arachidonic acid cascade in BEC. Results The results showed that (1) IV infection increases COX-2 expression, cPLA(2) phosphorylation and PGE(2) release, (2) ERK, p38 MAPK and INK were phosphorylated, (3) CEP-11004 and PD 98059 predominantly attenuated COX-2 expression and cPLA(2) phosphorylation, respectively, (4) SB 203580 did not remarkably affect COX-2 expression and cPLA(2) phosphorylation, and (5) each inhibitor dose-dependently attenuated PGE(2) release by various extents. Conclusion These results indicate that IV infection activates three distinct MAPKs, ERK, p38 MAPK and JNK, to participate to various extents in the induction of PGE(2) synthesis from arachidonic acid in BEC.