Lipoxin A(4) ameliorates lipopolysaccharide-induced lung injury through stimulating epithelial proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: LipoxinA(4) attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-019-1158-z) contains supplementary material, which is available to authorized users.