Abstract
Phosphatase and tensin homologue deleted on chromosome ten (PTEN) is part of a complex signaling system that affects a variety of important cell functions. PTEN blocks the action of PI3K by dephosphorylating the signaling lipid phosphatidylinositol 3,4,5-triphosphate. We have used a mouse model for asthma to determine the effect of PI3K inhibitors and PTEN on allergen-induced bronchial inflammation and airway hyperresponsiveness. PI3K activity increased significantly after allergen challenge. PTEN protein expression and PTEN activity were decreased in OVA-induced asthma. Immunoreactive PTEN localized in epithelial layers around the bronchioles in control mice. However, this immunoreactive PTEN dramatically disappeared in allergen-induced asthmatic lungs. The increased IL-4, IL-5, and eosinophil cationic protein levels in bronchoalveolar lavage fluids after OVA inhalation were significantly reduced by the intratracheal administration of PI3K inhibitors or adenoviruses carrying PTEN cDNA (AdPTEN). Intratracheal administration of PI3K inhibitors or AdPTEN remarkably reduced bronchial inflammation and airway hyperresponsiveness. These findings indicate that PTEN may play a pivotal role in the pathogenesis of the asthma phenotype.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Allergens / pharmacology
-
Androstadienes / pharmacology
-
Animals
-
Asthma / immunology*
-
Blood Proteins / biosynthesis
-
Blotting, Western
-
Bronchoalveolar Lavage Fluid
-
Cations
-
Cells, Cultured
-
Chromones / pharmacology
-
DNA, Complementary / metabolism
-
Dose-Response Relationship, Drug
-
Enzyme Inhibitors / pharmacology
-
Eosinophil Granule Proteins
-
Female
-
Genetic Vectors
-
Immunohistochemistry
-
Inflammation*
-
Interleukin-4 / biosynthesis
-
Interleukin-5 / biosynthesis
-
Lac Operon
-
Lung / immunology
-
Methacholine Chloride / pharmacology
-
Mice
-
Mice, Inbred BALB C
-
Morpholines / pharmacology
-
PTEN Phosphohydrolase
-
Phenotype
-
Phosphatidylinositol 3-Kinases / metabolism*
-
Phosphoric Monoester Hydrolases / immunology*
-
Phosphoric Monoester Hydrolases / physiology*
-
Phosphorylation
-
Ribonucleases*
-
Time Factors
-
Tumor Suppressor Proteins / immunology*
-
Tumor Suppressor Proteins / physiology*
-
Wortmannin
Substances
-
Allergens
-
Androstadienes
-
Blood Proteins
-
Cations
-
Chromones
-
DNA, Complementary
-
Enzyme Inhibitors
-
Eosinophil Granule Proteins
-
Interleukin-5
-
Morpholines
-
Tumor Suppressor Proteins
-
Methacholine Chloride
-
Interleukin-4
-
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
-
Phosphatidylinositol 3-Kinases
-
Ribonucleases
-
Phosphoric Monoester Hydrolases
-
PTEN Phosphohydrolase
-
Wortmannin