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ID 49929
FullText URL
Author
Yashiro, Masato Kaken ID
Tsukahara, Hirokazu
Matsukawa, Akihiro ORCID Kaken ID researchmap
Yamada, Mutsuko
Fujii, Yosuke
Nagaoka, Yoshiharu
Tsuge, Mitsuru
Yamashita, Nobuko Kaken ID researchmap
Yamada, Masao Kaken ID researchmap
Masutani, Hiroshi
Abstract
Objectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. Design: Prospective animal trial. Setting: Research laboratory. Subjects: Nine-week-old male C57BL/6 mice inoculated with H1N1. Intervention: The mice were divided into a vehicle-treated group and recombinant human thioredoxin-1-treated group. For survival rate analysis, the vehicle or recombinant human thioredoxin-1 was administered intraperitoneally every second day from day -1 to day 13. For lung lavage and pathological analyses, vehicle or recombinant human thioredoxin-1 was administered intraperitoneally on days 1, 1, and 3. Measurements and Main Results: Lung lavage and pathological analyses were performed at 24, 72, and 120 hrs after inoculation. The recombinant human thioredoxin-1 treatment significantly improved the survival rate of H1N1-inoculated mice, although the treatment did not affect virus propagation in the lung. The treatment significantly attenuated the histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice. The treatment significantly attenuated the production of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in the lung and oxidative stress enhancement, which were observed in H1N1-inoculated mice. H1N1 induced expressions of tumor necrosis factor-a and chemokine (C-X-C motif) ligand 1 in murine lung epithelial cells MLE-12, which were inhibited by the addition of recombinant human thioredoxin-1. The recombinant human thioredoxin-1 treatment started 30 mins after H1N1 inoculation also significantly improved the survival of the mice. Conclusions: Exogenous administration of recombinant human thioredoxin-1 significantly improved the survival rate and attenuated lung histological changes in the murine model of influenza pneumonia. The protective mechanism of thioredoxin-1 might be explained by its potent antioxidative and anti-inflammatory actions. Consequently, recombinant human thioredoxin-1 might be a possible pharmacological strategy for severe influenza virus infection in humans. (Crit Care Med 2013; 41:171-181)
Keywords
acute lung injury
cytokine
influenza virus
mouse
oxidative stress
thioredoxin-1
Published Date
2013-01
Publication Title
Critical Care Medicine
Volume
volume41
Issue
issue1
Start Page
171
End Page
181
ISSN
0090-3493
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1097/CCM.0b013e3182676352
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/49725
language
英語
File Version
author
Refereed
True
DOI
Web of Science KeyUT