Targeting phosphoinositide 3-kinase ? for the treatment of respiratory diseases
Asthma and chronic obstructive pulmonary disease (COPD) are characterized in their pathogenesis by chronic inflammation in the airways. Phosphoinositide 3-kinase ? (PI3K?), a lipid kinase expressed predominantly in leukocytes, is thought to hold much promise as a therapeutic target for such inflammatory conditions. Of particular interest for the treatment of severe respiratory disease is the observation that inhibition of PI3K? may restore steroid effectiveness under conditions of oxidative stress. PI3K? inhibition may also prevent recruitment of inflammatory cells, including T lymphocytes and neutrophils, as well as the release of proinflammatory mediators, such as cytokines, chemokines, reactive oxygen species, and proteolytic enzymes. In addition, targeting the PI3K? pathway could reduce the incidence of pathogen-induced exacerbations by improving macrophage-mediated bacterial clearance. In this review, we discuss the potential and highlight the unknowns of targeting PI3K? for the treatment of respiratory disease, focusing on recent developments in the role of the PI3K? pathway in inflammatory cell types believed to be critical to the pathogenesis of COPD.
asthma chronic obstructive pulmonary disease (copd) neutrophil respiratory inflammation t cell epithelial cell macrophage phosphoinositide 3-kinase (pi3k)