tetano
Editor, Senior Moderator
Front Immunol. 2014 Nov 5;5:561. eCollection 2014.
Therapeutic Impact of Human Serum Albumin-Thioredoxin Fusion Protein on Influenza Virus-Induced Lung Injury Mice.
Tanaka R1, Ishima Y2, Enoki Y1, Kimachi K3, Shirai T3, Watanabe H2, Chuang VT4, Maruyama T2, Otagiri M5.
Author information
Abstract
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 BALF 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? treatment also significantly suppressed the production of inflammatory cells and neutrophil infiltration, as well as the protein level in BALF and lung histopathological alterations caused by the influenza virus. The suppressive effect of Tamiflu? was slightly stronger than that of HSA-Trx. Interestingly, Tamiflu? 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.
KEYWORDS:
albumin; anti-oxidization; fusion; influenza virus; thioredoxin
PMID:
25414704
[PubMed - as supplied by publisher]
PMCID:
PMC4220708
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/25414704
Therapeutic Impact of Human Serum Albumin-Thioredoxin Fusion Protein on Influenza Virus-Induced Lung Injury Mice.
Tanaka R1, Ishima Y2, Enoki Y1, Kimachi K3, Shirai T3, Watanabe H2, Chuang VT4, Maruyama T2, Otagiri M5.
Author information
Abstract
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 BALF 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? treatment also significantly suppressed the production of inflammatory cells and neutrophil infiltration, as well as the protein level in BALF and lung histopathological alterations caused by the influenza virus. The suppressive effect of Tamiflu? was slightly stronger than that of HSA-Trx. Interestingly, Tamiflu? 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.
KEYWORDS:
albumin; anti-oxidization; fusion; influenza virus; thioredoxin
PMID:
25414704
[PubMed - as supplied by publisher]
PMCID:
PMC4220708
Free PMC Article
http://www.ncbi.nlm.nih.gov/pubmed/25414704