Protective Effects of Chymostatin on Paraquat-Induced Acute Lung Injury in Mice

This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydra...

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Bibliographic Details
Published in:Inflammation 2018-02, Vol.41 (1), p.122-133
Main Authors: Yang, Chen, Song, Hong-wei, Liu, Wei, Dong, Xue-song, Liu, Zhi
Format: Article
Language:English
Subjects:
Alveolitis
Biomedical and Life Sciences
Biomedicine
Cancer
Cathepsin G
Chloral hydrate
Edema
Endothelial cells
Enzyme-linked immunosorbent assay
Heart diseases
HMGB1 protein
Immunology
Inflammation
Interleukin 6
Internal Medicine
Lung cancer
Original Article
Paraquat
Pathology
Pharmacology/Toxicology
Rheumatology
Rodents
Serum levels
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Tumors
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Summary:This study aims to evaluate the role of chymostatin in paraquat-induced acute lung injury. Institute of Cancer Research mice were randomly distributed into the NS, DMSO, chymostatin, paraquat or chymostatin treatment groups. Six mice from each group were intraperitoneally injected with chloral hydrate at 0, 1, 2, 4, 8, 12, 24 and 48 h after treatment administration. Blood samples were collected through cardiac puncture. Lung tissues were stained with haematoxylin and eosin for the observation of lung histology. The degree of pulmonary oedema was determined on the basis of lung wet-to-dry ratio (W/D). The serum activity of cathepsin G was determined through substrate fluorescence assay. The serum levels of endothelial cell-specific molecule-1 (endocan), tumour necrosis factor-a (TNF-a), interleukin-1β (IL-1β), IL-6 and high-mobility group box protein 1 (HMGB1) were determined through enzyme-linked immunosorbent assay. The expression levels of endocan and nuclear NF-κBp65 in the lung were quantified through Western blot. Chymostatin alleviated the pathological changes associated with acute alveolitis in mice; decreased the lung W/D ratio, the activity of cathepsin G and the serum concentrations of TNF-a, IL-1β, IL-6 and HMGB1; and increased the serum concentration of endocan. Western blot results revealed that chymostatin up-regulated endocan expression and down-regulated nuclear NF-κBp65 expression in the lung. Chymostatin reversed the inflammatory effects of paraquat-induced lung injury by inhibiting cathepsin G activity to up-regulate endocan expression and indirectly inhibit NF-κBp65 activity.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-017-0670-x