Preventive and therapeutic effects of phosphoinositide 3-kinase inhibitors on acute lung injury

Background: Phosphoinositide 3-kinases (PI3Ks) are involved in a number of biological responses. Recent preclinical studies demonstrated that PI3K-dominent signal pathway could play an important and critical role in the development of acute lung injury, while the number of studies are limited and the mechanism remains unclear. Methods: CD-1 mice were intranasally or intragastrically administered with different PI3K inhibitors once a day for three days before intratracheal instillation of LPS for 4 and 24 hours. Effects of SHBM1009 on LPS-induced capillary permeability, leukocyte distribution and epithelial cells were measured. Besides, the therapeutic effects of SHBM1009 on pancreatic elastase induced lung injury was evaluated in wistar rats. Results: Local delivery of PI3K inhibitors had more effective roles in the prevention from LPS-induced ALI than systemic delivery. PI3K inhibitors prevented both LPS- or elastase-induced lung injury in mice and rats probably through the directly inhibitory effects on airway epithelial cells, activating neutrophils and macrophages. Conclusion: PI3K may be a therapeutic target for lung injury.