Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Lipoxins (LXs), as so-called “braking signals” of inflammation, are the first mediators identified to have dual anti-inflammatory and inflammatory pro-resolving properties.
In vivo, lipoxinA 4 was administrated intraperitoneally with 1 μg/per mouse after intra-tracheal LPS administration (10 mg/kg). Apoptosis, proliferation and epithelial–mesenchymal transition of AT II cells were measured by immunofluorescence. In vitro, primary human alveolar type II cells were used to model the effects of lipoxin A 4 upon proliferation, apoptosis and epithelial–mesenchymal transition.
In vivo, lipoxin A 4 markedly promoted alveolar epithelial type II cells (AT II cells) proliferation, inhibited AT II cells apoptosis, reduced cleaved caspase-3 expression and epithelial–mesenchymal transition, with the outcome of attenuated LPS-induced lung injury. In vitro, lipoxin A 4 increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA 4 also inhibited epithelial mesenchymal transition in response to TGF-β 1, which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA 4 on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A 4 significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-β 1 in primary human AT II cells.