Abstract |
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.
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Authors | Dan Zhang, Jian Zhou, Le Chi Ye, Jing Li, Zhenzhou Wu, Yuping Li, Chichi Li |
Journal | Journal of cellular physiology
(J Cell Physiol)
Vol. 233
Issue 1
Pg. 688-698
(Jan 2018)
ISSN: 1097-4652 [Electronic] United States |
PMID | 28328069
(Publication Type: Journal Article)
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Copyright | © 2017 Wiley Periodicals, Inc. |
Chemical References |
- ATG5 protein, human
- Autophagy-Related Protein 5
- Lipopolysaccharides
- TJP1 protein, human
- Zonula Occludens-1 Protein
- Atg7 protein, human
- Autophagy-Related Protein 7
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Topics |
- Acute Lung Injury
(chemically induced, genetics, metabolism, pathology)
- Animals
- Autophagy
- Autophagy-Related Protein 5
(genetics, metabolism)
- Autophagy-Related Protein 7
(genetics, metabolism)
- Blood-Air Barrier
(metabolism, ultrastructure)
- Capillary Permeability
- Cells, Cultured
- Disease Models, Animal
- Endothelial Cells
(metabolism, ultrastructure)
- Humans
- Lipopolysaccharides
- Lung
(blood supply, metabolism, ultrastructure)
- Mice, Inbred C57BL
- Pulmonary Edema
(chemically induced, metabolism, pathology)
- RNA Interference
- Stress Fibers
(metabolism)
- Transfection
- Zonula Occludens-1 Protein
(metabolism)
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