title: Phosphatidylinositol 3-kinase is required for rhinovirus-induced airway epithelial cell interleukin-8 expression.
abstract: Rhinovirus (RV) is a common cause of asthma exacerbations. The signaling mechanisms regulating RV-induced airway epithelial cell responses have not been well studied. We examined the role of phosphatidylinositol (PI) 3-kinase in RV-induced interleukin (IL)-8 expression. Infection of 16HBE14o- human bronchial epithelial cells with RV39 induced rapid activation of PI 3-kinase and phosphorylation of Akt, a downstream effector of PI 3-kinase. RV39 also colocalized with cit-Akt-PH, a citrogen-tagged fluorescent fusion protein encoding the pleckstrin homology domain of Akt, indicating that 3-phosphorylated PI accumulates at the site of RV infection. Inhibition of PI 3-kinase and Akt attenuated RV39-induced NF-kappaB transactivation and IL-8 expression. Inhibition of PI 3-kinase also blocked internalization of labeled RV39 into 16HBE14o- cells, suggesting that the requirement of PI 3-kinase for RV39-induced IL-8 expression, at least in part, relates to its role in viral endocytosis.
authors.affiliation: Department of Pediatrics, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: Uma
authors.initials: U
authors.lastname: Sajjan
authors.forename: Suparna
authors.initials: S
authors.lastname: Nanua
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.forename: Adam M
authors.initials: AM
authors.lastname: Goldsmith
authors.forename: J Kelley
authors.initials: JK
authors.lastname: Bentley
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012137:Respiratory System / Q000166:cytology / Q000201:enzymology*; D012229:Rhinovirus / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt