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.
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Authors | Dawn C Newcomb, Uma Sajjan, Suparna Nanua, Yue Jia, Adam M Goldsmith, J Kelley Bentley, Marc B Hershenson |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 280
Issue 44
Pg. 36952-61
(Nov 04 2005)
ISSN: 0021-9258 [Print] United States |
PMID | 16120607
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Interleukin-8
- NF-kappa B
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
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Topics |
- Bronchi
(cytology, metabolism)
- Cells, Cultured
- Electrophoretic Mobility Shift Assay
- Epithelial Cells
(cytology, enzymology)
- Humans
- Interleukin-8
(genetics, metabolism)
- NF-kappa B
(metabolism)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Promoter Regions, Genetic
- Proto-Oncogene Proteins c-akt
(metabolism)
- Respiratory System
(cytology, enzymology)
- Rhinovirus
(physiology)
- Transcription, Genetic
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