Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma
Yong-Geun Kwak, … , Kyung S. Lee, Yong C. Lee
Yong-Geun Kwak, … , Kyung S. Lee, Yong C. Lee
Published April 1, 2003
Citation Information: J Clin Invest. 2003;111(7):1083-1092. https://doi.org/10.1172/JCI16440.
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Article

Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma

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.

Authors

Yong-Geun Kwak, Chang H. Song, Ho K. Yi, Pyoung H. Hwang, Jong-Suk Kim, Kyung S. Lee, Yong C. Lee

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Figure 5

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Localization of immunoreactive PTEN in lung tissues and tracheal epithel...
Localization of immunoreactive PTEN in lung tissues and tracheal epithelial cells of OVA-sensitized and -challenged mice. Sampling was performed 72 hours after the last challenge in lung tissues and tracheal epithelial cells from sensitized mice challenged with saline (a and e), from sensitized mice challenged with OVA (b and f), from OVA-inhaled mice administered AdPTEN (c), and from OVA-inhaled mice administered AdLacZ (d). Representative light microscopy shows PTEN-positive cells in the bronchioles (a, b, c, and d; the brown color indicates PTEN-positive cells) and in the tracheal epithelial cells (e and f; the dark brown color indicates PTEN-positive cells). Bars indicate scale of 50 μm (a, b, c, and d) or 10 μm (e and f).