Contribution of CFTR to Alveolar Fluid Clearance by Lipoxin A4 via PI3K/Akt Pathway in LPS-Induced Acute Lung Injury

The lipoxins are the first proresolution mediators to be recognized and described as the endogenous "braking signals" for inflammation. We evaluated the anti-inflammatory and proresolution bioactions of lipoxin A(4) in our lipopolysaccharide (LPS-) induced lung injury model. We demonstrated that lipoxin A(4) significantly improved histology of rat lungs and inhibited IL-6 and TNF-alpha in LPS-induced lung injury. In addition, lipoxin A(4) increased alveolar fluid clearance (AFC) and the effect of lipoxin A(4) on AFC was abolished by CFTRinh-172 (a specific inhibitor of CFTR). Moreover, lipoxin A(4) could increase cystic fibrosis transmembrane conductance regulator (CFTR) protein expression in vitro and in vivo. In rat primary alveolar type II (ATII) cells, LPS decreased CFTR protein expression via activation of PI3K/Akt, and lipoxin A(4) suppressed LPS-stimulated phosphorylation of Akt. These results showed that lipoxin A(4) enhanced CFTR protein expression and increased AFC via PI3K/Akt pathway. Thus, lipoxin A(4) may provide a potential therapeutic approach for acute lung injury.