Abstract
BackgroundAcute 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.MethodsIn vivo, lipoxinA4 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 A4 upon proliferation, apoptosis and epithelial–mesenchymal transition.ResultsIn vivo, lipoxin A4 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 A4 increased primary human alveolar epithelial type II cells (AT II cells) proliferation and reduced LPS induced AT II cells apoptosis. LipoxinA4 also inhibited epithelial mesenchymal transition in response to TGF-β1, which was lipoxin receptor dependent. In addition, Smad3 inhibitor (Sis3) and PI3K inhibitor (LY294002) treatment abolished the inhibitory effects of lipoxinA4 on the epithelial mesenchymal transition of primary human AT II cells. Lipoxin A4 significantly downregulated the expressions of p-AKT and p-Smad stimulated by TGF-β1 in primary human AT II cells.ConclusionLipoxinA4 attenuates lung injury via stimulating epithelial cell proliferation, reducing epithelial cell apoptosis and inhibits epithelial–mesenchymal transition.
Highlights
Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption
Immunofluorescence staining of lung specimens was shot by fluorescence microscope and calculated by positive goals compared to DAPI. a-h: Immunofluorescence staining of marker of epithelial-mesenchymal transition (EMT) (× 400): E-cadherin(a-b), N-cadherin(c-d), α-Smooth muscle actin (α-SMA)(e-f) and Vimentin(g-h). i and j: co-dying of SP-C and α-SMA. scar bar = 50 μm
Our study demonstrated that Lipoxin A4 (LXA4) alleviated lung injury via promoting type Human Alveolar Type II (II) alveolar lung epithelial cell proliferation, whilst inhibiting apoptosis and decreasing caspase-3 activation in an intratracheal LPS murine model of Acute lung injury (ALI)/ARDS
Summary
Acute respiratory distress syndrome (ARDS) is characterized by alveolar epithelial disruption. Acute respiratory distress syndrome (ARDS), an acute inflammatory pulmonary process, causes intense and diffuse alveolar architecture damage and the development of interstitial and alveolar protein-rich edema, leading to acute hypoxemic respiratory failure [1, 2]. In ARDS, the alveolar epithelium is the primary target where cell damage occurs. The degree of alveolar epithelial damage can predict the outcome of ARDS [3, 4]. The repair of the alveolar epithelium plays a crucial role in the resolution of ARDS [4]. Recent literatures have demonstrated that apoptosis of alveolar epithelial cells contributed to the loss of alveolar epithelial cells and the development of ARDS [5,6,7]. Inhibiting apoptosis has been shown to attenuate lung injury in animal models [6]
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