Role of oxidants in influenza virus-induced gene expression

Katharine Knobil, Augustine M.K. Choi, Gordon W. Weigand, David B. Jacoby

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Influenza virus-induced epithelial damage may be mediated, in part, by reactive oxygen intermediates (ROIs). In this study, we investigated the role of ROIs in the influenza virus-induced gene expression of antioxidant enzymes and in the activation of nuclear factor-κB (NF-κB), an oxidant-sensitive transcriptional factor. Influenza virus infection increased production of intracellular ROIs in A549 pulmonary epithelial cells. Induction of manganese superoxide dismutase (MnSOD) mRNA correlated with increased MnSOD protein and enzyme activity. Influenza virus infection also activated NF-κB binding as determined by an electrophoretic mobility shift assay. Pretreatment of A549 cells with N-acetyl-L-cysteine attenuated virus-induced NF-κB activation and interleukin (IL)-8 mRNA induction but did not block induction of MnSOD mRNA. In contrast, pyrrolidine dithiocarbamate blocked activation of NF-κB and induction of MnSOD and IL-8 mRNAs. Treatment with pyrrolidine dithiocarbamate also markedly decreased virus-induced cell death. Thus oxidants are involved in influenza virus-induced activation of NF-κB, in the expression of IL-8 and MnSOD, and in virus-induced cell death.

Original languageEnglish (US)
Pages (from-to)L134-L142
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number1 18-1
DOIs
StatePublished - Jan 1998
Externally publishedYes

Keywords

  • Interleukin-8
  • Manganese superoxide dismutase
  • N-acetyl-L- cysteine
  • Nuclear factor-κB
  • Pyrrolidine dithiocarbamate

ASJC Scopus subject areas

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

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