Antioxidant mimetics modulate oxidative stress and cellular signaling in airway epithelial cells infected with respiratory syncytial virus

Yashoda M. Hosakote, Narayana Komaravelli, Nicolas Mautemps, Tianshuang Liu, Roberto P. Garofalo, Antonella Casola

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Respiratory syncytial virus (RSV) is one of the most common causes of bronchiolitis and pneumonia among infants and young children worldwide. In previous investigations, we have shown that RSV infection induces rapid generation of reactive oxygen species (ROS), which modulate viral-induced cellular signaling, and downregulation of antioxidant enzyme (AOE) expression, resulting in oxidative stress in vitro and in vivo, which plays a pathogenetic role in RSV-induced lung disease. In this study, we determined whether pharmacological intervention with synthetic catalytic scavengers could reduce RSVinduced proinflammatory gene expression and oxidative cell damage in an in vitro model of infection. Treatment of airway epithelial cells (AECs) with the salen-manganese complexes EUK-8 or EUK-189, which possess superoxide dismutase, catalase, and glutathione peroxidase activity, strongly reduced RSV-induced ROS formation by increasing cellular AOE enzymatic activity and levels of the lipid peroxidation products F2-8-isoprostane and malondialdehyde, which are markers of oxidative stress. Treatment of AECs with AOE mimetics also significantly inhibited RSV-induced cytokine and chemokine secretion and activation of the transcription factors nuclear factor-=B and interferon regulatory factor-3, which orchestrate proinflammatory gene expression. Both EUKs were able to reduce viral replication, when used at high doses. These results suggest that increasing antioxidant cellular capacities can significantly impact RSV-associated oxidative cell damage and cellular signaling and could represent a novel therapeutic approach in modulating virusinduced lung disease.

Original languageEnglish (US)
Pages (from-to)L991-L1000
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume303
Issue number11
DOIs
StatePublished - Dec 17 2012

Keywords

  • Airway epithelial cells
  • Antioxidant enzyme mimetics
  • Oxidative stress
  • Respiratory syncytial virus

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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