PTEN/PI3K pathway as a therapeutic target for allergic airways inflammation

Asthma is a common lung disease that is characterized by chronic airways inflammation and variable airflow obstruction with airways hyperresponsiveness. Recent studies highlight the importance of the underlying inflammatory cascade, particularly signaling pathways, in the pathogenesis of asthma. Phosphatase and tensin homolog (PTEN) is a complex signaling molecule that regulates important biological processes such as the metabolism, proliferation and survival of cells. PTEN antagonizes the action of phosphoinositide 3-kinase (PI3K) by dephosphorylating phosphatidylinositol 3,4,5-trisphosphate. There is increasing evidence that the PTEN/PI3K pathway plays a major role in the expression and activation of inflammatory mediators, inflammatory cell recruitment and immune cell function, thereby contributing to the pathogenesis of asthma. Upregulation of PTEN expression or inhibition of PI3K activity leads to the attenuation of allergic airways inflammation and bronchial hyperresponsiveness by modulating multiple regulatory pathways in asthma. This review describes recent advances in understanding the role and related mechanisms of the PTEN/PI3K pathway in regulating allergic airways inflammation and the potential for targeting this pathway for the treatment of asthma.