tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2012 Sep 20. [Epub ahead of print]
Glutathione Peroxidase-1 (GPx-1) Reduces Influenza A Virus-Induced Lung Inflammation.
Yatmaz S, Seow HJ, Gualano RC, Wong ZX, Stambas J, Selemidis S, Crack PJ, Bozinovski S, Anderson GP, Vlahos R.
Source
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Abstract
Oxidative stress caused by excessive reactive oxygen species production is implicated in influenza A virus-induced lung disease. Glutathione peroxidase-1 (GPx-1) is an antioxidant enzyme that may protect lungs from such damage. The objective of this study was to determine if GPx-1 protects the lung against influenza A virus-induced lung inflammation in vivo. Male wild-type (WT) or GPx-1(-/-)mice were inoculated with HKx31 (H3N2, 1x10(4) PFU) and bronchoalveolar lavage fluid (BALF)/lung compartments analysed on days 3 (d3) and 7 (d7) post infection (p.i.) for inflammatory marker expression, histology and viral titre. WT mice infected with HKx31 had significantly more BALF total cells, macrophages, neutrophils and lymphocytes at d3 and d7 compared to na?ve WT animals (n=5-8, P<0.05). However, infected GPx-1(-/-) mice had significantly more BALF inflammation which included more total cells, macropahges and neutrophils, compared to WT mice, and this was abolished by treatment with the GPx mimetic ebselen. Of interest was that BALF inflammation persisted in GPx-1(-/-) mice d10 pi. and that GPx-1(-/-) mice had significantly more influenza specific CD8+ T cells in spleen compared with WT mice (n=3-4, P<0.05). Infected GPx-1(-/-) mice had greater peribronchial and parenchymal inflammation than WT mice and viral titre was significantly reduced in GPx-1(-/-) mice at d3 (n=5, P<0.05). Gene expression analysis revealed that infected GPx-1(-/-) mice had higher whole lung TNF-α, MIP-1α, MIP-2, KC, and MMP-12 mRNA compared to infected WT mice. GPx-1(-/-) mice had more MIP-2 protein in BALF at d3 and more active MMP-9 protease in BALF at d3 and d7 than WT mice. These data indicate that GPx-1 reduces influenza A virus-induced lung inflammation.
PMID:
23002098
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23002098
Glutathione Peroxidase-1 (GPx-1) Reduces Influenza A Virus-Induced Lung Inflammation.
Yatmaz S, Seow HJ, Gualano RC, Wong ZX, Stambas J, Selemidis S, Crack PJ, Bozinovski S, Anderson GP, Vlahos R.
Source
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia.
Abstract
Oxidative stress caused by excessive reactive oxygen species production is implicated in influenza A virus-induced lung disease. Glutathione peroxidase-1 (GPx-1) is an antioxidant enzyme that may protect lungs from such damage. The objective of this study was to determine if GPx-1 protects the lung against influenza A virus-induced lung inflammation in vivo. Male wild-type (WT) or GPx-1(-/-)mice were inoculated with HKx31 (H3N2, 1x10(4) PFU) and bronchoalveolar lavage fluid (BALF)/lung compartments analysed on days 3 (d3) and 7 (d7) post infection (p.i.) for inflammatory marker expression, histology and viral titre. WT mice infected with HKx31 had significantly more BALF total cells, macrophages, neutrophils and lymphocytes at d3 and d7 compared to na?ve WT animals (n=5-8, P<0.05). However, infected GPx-1(-/-) mice had significantly more BALF inflammation which included more total cells, macropahges and neutrophils, compared to WT mice, and this was abolished by treatment with the GPx mimetic ebselen. Of interest was that BALF inflammation persisted in GPx-1(-/-) mice d10 pi. and that GPx-1(-/-) mice had significantly more influenza specific CD8+ T cells in spleen compared with WT mice (n=3-4, P<0.05). Infected GPx-1(-/-) mice had greater peribronchial and parenchymal inflammation than WT mice and viral titre was significantly reduced in GPx-1(-/-) mice at d3 (n=5, P<0.05). Gene expression analysis revealed that infected GPx-1(-/-) mice had higher whole lung TNF-α, MIP-1α, MIP-2, KC, and MMP-12 mRNA compared to infected WT mice. GPx-1(-/-) mice had more MIP-2 protein in BALF at d3 and more active MMP-9 protease in BALF at d3 and d7 than WT mice. These data indicate that GPx-1 reduces influenza A virus-induced lung inflammation.
PMID:
23002098
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23002098