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The Role of Glutathione Reductase in Influenza Infection

Title
The Role of Glutathione Reductase in Influenza Infection
Authors
Hong, Kyung SookPagan, KassandraWhalen, WilliamHarris, RebeccaYang, JianjunStout-Delgado, HeatherCho, Soo Jung
Ewha Authors
홍경숙
SCOPUS Author ID
홍경숙scopus
Issue Date
2022
Journal Title
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
ISSN
1044-1549JCR Link

1535-4989JCR Link
Citation
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY vol. 67, no. 4, pp. 438 - 445
Keywords
influenzapneumoniaglutathione metabolismcell death
Publisher
AMER THORACIC SOC
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Influenza infection induces lung epithelial cell injury via programmed cell death. Glutathione, a potent antioxidant, has been reported to be associated with influenza infection. We hypothesized that lung epithelial cell death during influenza infection is regulated by glutathione metabolism. Eight-week-old male and female BALB/c mice were infected with influenza (PR8: A/PR/8/34 [H1N1]) via intranasal instillation. Metabolomic analyses were performed on whole lung lysate after influenza infection. For in vitro analysis, Beas-2B cells were infected with influenza. RNA was extracted, and QuantiTect Primer Assay was used to assess gene expression. Glutathione concentrations were assessed by colorimetric assay. Influenza infection resulted in increased inflammation and epithelial cell injury in our murine model, leading to increased morbidity and mortality. In both our in vivo and in vitro models, influenza infection was found to induce apoptosis and necroptosis. Influenza infection led to decreased glutathione metabolism and reduced glutathione reductase activity in lung epithelial cells. Genetic inhibition of glutathione reductase suppressed apoptosis and necroptosis of lung epithelial cells. Pharmacologic inhibition of glutathione reductase reduced airway inflammation, lung injury, and cell death in our murine influenza model. Our results demonstrate that glutathione reductase activity is suppressed during influenza. Glutathione reductase inhibition prevents epithelial cell death and morbidity in our murine influenza model. Our results suggest that glutathione reductase-dependent glutathione metabolism may play an important role in the host response to viral infection by regulating lung epithelial cell death.
DOI
10.1165/rcmb.2021-0372OC
Appears in Collections:
의과대학 > 의학과 > Journal papers
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