title: Role of mitogen-activated protein kinases in influenza virus induction of prostaglandin E2 from arachidonic acid in bronchial epithelial cells.
abstract: 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 A2 (cPLA2) phosphorylation and prostaglandin E2 (PGE2) 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 cPLA2 and phosphorylation of ERK, JNK and p38 MAPK were determined by Western blot. The concentrations of PGE2 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, cPLA2 phosphorylation and PGE2 release, (2) ERK, p38 MAPK and JNK were phosphorylated, (3) CEP-11004 and PD 98059 predominantly attenuated COX-2 expression and cPLA2 phosphorylation, respectively, (4) SB 203580 did not remarkably affect COX-2 expression and cPLA2 phosphorylation, and (5) each inhibitor dose-dependently attenuated PGE2 release by various extents.
  
  
  CONCLUSIONS
  These results indicate that IV infection activates three distinct MAPKs, ERK, p38 MAPK and JNK, to participate to various extents in the induction of PGE2 synthesis from arachidonic acid in BEC.
authors.affiliation: First Department of Internal Medicine, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Mizumura
authors.forename: S
authors.initials: S
authors.lastname: Hashimoto
authors.forename: S
authors.initials: S
authors.lastname: Maruoka
authors.forename: Y
authors.initials: Y
authors.lastname: Gon
authors.forename: N
authors.initials: N
authors.lastname: Kitamura
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Horie
mesh_terms: D016718:Arachidonic Acid / Q000378:metabolism*; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007251:Influenza, Human / Q000276:immunology* / Q000378:metabolism; D007527:Isoenzymes / Q000032:analysis; D048031:JNK Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000276:immunology; D008565:Membrane Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000276:immunology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010766:Phosphorylation; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone