論文

査読有り
2014年11月

Therapeutic impact of human serum albumin-thioredoxin fusion protein on influenza virus-inducec lung injury mice

FRONTIERS IN IMMUNOLOGY
  • Ryota Tanaka
  • ,
  • Yu Ishima
  • ,
  • Yuki Enoki
  • ,
  • Kazuhiko Kimachi
  • ,
  • Tatsuya Shirai
  • ,
  • Hiroshi Watanabe
  • ,
  • Victor T. G. Chuang
  • ,
  • Toru Maruyama
  • ,
  • Masaki Otagiri

5
開始ページ
561
終了ページ
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3389/fimmu.2014.00561
出版者・発行元
FRONTIERS RESEARCH FOUNDATION

Reactive oxygen species (ROS) are the primary pathogenic molecules produced in viral lung infections. We previously reported on the use of a recombinant human serum albumin (HSA)-thioredoxin 1 (Trx) fusion protein (HSA-Trx) for extending the half-life Trx, an endogenous protein with anti-oxidant properties. As a result, it was possible to overcome the unfavorable pharmacokinetic and short pharmacological properties of Trx. We hypothesized that HSA-Trx would attenuate the enhanced ROS production of species such as hydroxyl radicals by neutrophils during an influenza viral infection. The levels of 8-hydroxy-2'-deoxyguanosine and 3-nitrotyrosine were used as indices of the anti-oxidant activity of HSA Trx. In addition, the cytoprotective effects of HSA Trx were examined in PR8 (H1N1) influenza virus-induced lung injured mice. The findings show that HSA-Trx reduced the number of total cells, neutrophils, and total protein in BALE of influenza virus-induced lung injured mice. The HSA-Trx treatment significantly decreased the level of 8-hydroxy-2'-deoxyguanosine and 3-nitrotyrosine, but failed to inhibit inducible nitric oxide synthase expression, in the lungs of the virus-infected mice. On the other hand, Tamiflu (R) treatment also significantly suppressed the production of inflammatory cells and neutrophil infiltration, as well as the protein level in BALE and lung histopathological alterations caused by the influenza virus. The suppressive effect of Tamiflu (R) was slightly stronger than that of HSA-Trx. Interestingly, Tamiflu (R) significantly decreased virus proliferation, while HSA-Trx had no effect. These results indicate that HSA-Trx may be of therapeutic value for the treatment of various acute inflammatory disorders such as influenza-virus-induced pneumonia, by inhibiting inflammatory-cell responses and suppressing the overproduction of NO in the lung.

Web of Science ® 被引用回数 : 19

リンク情報
DOI
https://doi.org/10.3389/fimmu.2014.00561
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25414704
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000354521400001&DestApp=WOS_CPL
ID情報
  • DOI : 10.3389/fimmu.2014.00561
  • ISSN : 1664-3224
  • PubMed ID : 25414704
  • Web of Science ID : WOS:000354521400001

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