Autophagy maintains the integrity of endothelial barrier in LPS-induced lung injury.
Understanding the role and underlying regulation mechanism of autophagy in lipopolysaccharide-induced lung injury (LPS-LI) may provide potentially new pharmacological targets for treatment of acute lung injury. The aim of this study was to investigate the functional significance of autophagy in LPS-LI. The autophagy of human pulmonary microvascular endothelial cells (HPMVECs) and mice was inhibited before they were challenged with LPS. In vitro, permeability, vitality, and the LDH release rate of the cells were detected, the zonula occluden-1 (ZO-1) expression and the stress fiber formation were determined. In vivo, the lung injury was assessed. We found LPS caused high permeability and increased lactate dehydrogenase (LDH) release rate, lowered viability of the cells, inhibited the ZO-1 expression and induced stress fiber formation, these effects were further aggravated by prohibiting the level of autophagy. Consistently, in in vivo experiments, LPS-induced serious lung injury, which was reflected as edema, leukocyte infiltration and hemorrhage in lung tissue, and the high concentration of pro-inflammation cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β in bronchoalveolar lavage fluid (BALF). Inhibiting autophagy further exacerbated LPS-LI. It appears that autophagy played a protective role in LPS-LI in part through restricting the injury of lung microvascular barrier.
Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Dan
D
Zhang
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Jian
J
Zhou
Department of Oncological Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Le Chi
LC
Ye
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, P.R. China.
Jing
J
Li
Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Zhenzhou
Z
Wu
Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Yuping
Y
Li
Department of Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province, P.R. China.
Chichi
http://orcid.org/0000-0002-1850-5336
C
Li
D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001343:Autophagy; D000071187:Autophagy-Related Protein 5 / Q000235:genetics / Q000378:metabolism; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000378:metabolism; D015824:Blood-Air Barrier / Q000378:metabolism* / Q000648:ultrastructure; D002199:Capillary Permeability; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008070:Lipopolysaccharides; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000648:ultrastructure; D008810:Mice, Inbred C57BL; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D022502:Stress Fibers / Q000378:metabolism; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
C502778:ATG5 protein, human; D000071187:Autophagy-Related Protein 5; D008070:Lipopolysaccharides; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7
acute lung injury; autophagy; lipopolysaccharide; microvascular barrier