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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Schematic diagram of the experimental protocol. Mice were sensitized on ...
Schematic diagram of the experimental protocol. Mice were sensitized on days 1 and 14 by intraperitoneal injection of OVA emulsified in 1 mg aluminum hydroxide. On days 21, 22, and 23 after the initial sensitization, the mice were challenged for 30 minutes with an aerosol of 1% (wt/vol) OVA in saline (or with saline as a control) using an ultrasonic nebulizer. Wortmannin, LY-294002, or Ad vector was administered intratracheally two times to each treated animal, once on day 21 (1 hour before the first airway challenge with OVA) and the second time on day 23 (3 hours after the last airway challenge with OVA).