Expression of DEL-1 in alveolar epithelial cells prevents lipopolysaccharide-induced inflammation, oxidative stress, and eosinophil recruitment in acute lung injury

Abstract

Bacterial infection is a major cause of acute lung injury (ALI). Developmental endothelial locus-1 (DEL-1) is an immunomodulatory mediator secreted by the endothelial cells. This study aimed to investigate the role of DEL-1 in lipopolysaccharide (LPS)-induced ALI in mouse models and its ability to regulate on eosinophil recruitment. Male C57BL/6 mice were administered an adeno-associated virus (AAV)-mediated DEL-1 overexpression vector via intratracheal injection. Twenty-one days after vector instillation, mice were challenged with LPS (5 mg/kg body weight). Lung injury was evaluated using haematoxylin–eosin staining, flow cytometry, enzyme-linked immunosorbnent assay, quantitative real-time polymerase chain reaction, western blotting, immunohistochemistry and immunofluorescence analyses. DEL-1 was expressed in alveolar epithelial cells of mice. Compared with that in the control group, DEL-1 was expressed at low levels in the lungs of LPS-challenged mice. LPS injured the lungs in mice, as evidenced by an increase in alveolar wall thickness, inflammatory cell infiltration in the stroma, and alveolar collapse. AAV-mediated DEL-1 overexpression attenuated LPS-induced lung injury and inhibited the release of TNF-α, IL-6, and IL-1β. DEL-1 overexpression also attenuated LPS-induced oxidative stress by decreasing lactic dehydrogenase (LDH), myeloperoxidase (MPO), malondialdehyde (MDA), and reactive oxygen species (ROS) activities and increasing superoxide dismutase (SOD) activity. In addition, DEL-1 prevented eosinophil recruitment into lung tissues and inhibited eotaxin production. This study revealed the beneficial role of DEL-1 in preventing LPS-induced ALI in mice. Therefore, DEL-1 can protect lung tissues against LPS-induced inflammation, oxidative stress, and eosinophil recruitment.