ID | 49929 |
フルテキストURL | |
著者 |
Yashiro, Masato
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Kaken ID
Tsukahara, Hirokazu
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Matsukawa, Akihiro
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med
ORCID
Kaken ID
publons
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Yamada, Mutsuko
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Fujii, Yosuke
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Nagaoka, Yoshiharu
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Tsuge, Mitsuru
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Yamashita, Nobuko
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pediat
Kaken ID
publons
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Ito, Toshihiro
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pathol & Expt Med
ORCID
Kaken ID
publons
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Yamada, Masao
Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Virol
Kaken ID
publons
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Masutani, Hiroshi
Kyoto Univ, Inst Virus Res, Dept Biol Responses
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抄録 | 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)
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キーワード | acute lung injury
cytokine
influenza virus
mouse
oxidative stress
thioredoxin-1
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発行日 | 2013-01
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出版物タイトル |
Critical Care Medicine
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巻 | 41巻
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号 | 1号
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開始ページ | 171
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終了ページ | 181
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ISSN | 0090-3493
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1097/CCM.0b013e3182676352
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関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/49725
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言語 |
英語
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |