Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway

Hemalatha Indukuri, Shawn M. Castro, Sha Mei Liao, Lee Ann Feeney, Marion Dorsch, Anthony J. Coyle, Roberto Garofalo, Allan R. Brasier, Antonella Casola

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection induces expression and catalytic activity of IKKε, a noncanonical IKK-like kinase. Expression of a kinase-inactive IKKε blocks RSV-induced IRF-3 serine phosphorylation, nuclear translocation and DNA-binding, leading to inhibition of RANTES gene transcription, mRNA expression and protein synthesis. Treatment of alveolar epithelial cells with antioxidants or with NAD(P)H oxidase inhibitors abrogates RSV-induced chemokine secretion, IRF-3 phosphorylation and IKKε induction, indicating that ROS generation plays a fundamental role in the signaling pathway leading to IRF-3 activation, therefore, identifying a novel molecular target for the development of strategies aimed to modify the inflammatory response associated with RSV infection of the lung.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalVirology
Volume353
Issue number1
DOIs
StatePublished - Sep 15 2006

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I-kappa B Kinase
Interferon Regulatory Factor-3
Respiratory Syncytial Viruses
Oxidation-Reduction
Respiratory Syncytial Virus Infections
Chemokines
Reactive Oxygen Species
Phosphotransferases
Phosphorylation
Alveolar Epithelial Cells
Chemokine CCL5
NADPH Oxidase
Serine
Transcription Factors
Antioxidants
viral interferon regulatory factors
Gene Expression
Lung
Messenger RNA
DNA

Keywords

  • Airway epithelial cells
  • Inflammation
  • IRF
  • ROS
  • RSV

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway. / Indukuri, Hemalatha; Castro, Shawn M.; Liao, Sha Mei; Feeney, Lee Ann; Dorsch, Marion; Coyle, Anthony J.; Garofalo, Roberto; Brasier, Allan R.; Casola, Antonella.

In: Virology, Vol. 353, No. 1, 15.09.2006, p. 155-165.

Research output: Contribution to journalArticle

Indukuri, H, Castro, SM, Liao, SM, Feeney, LA, Dorsch, M, Coyle, AJ, Garofalo, R, Brasier, AR & Casola, A 2006, 'Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway', Virology, vol. 353, no. 1, pp. 155-165. https://doi.org/10.1016/j.virol.2006.05.022
Indukuri, Hemalatha ; Castro, Shawn M. ; Liao, Sha Mei ; Feeney, Lee Ann ; Dorsch, Marion ; Coyle, Anthony J. ; Garofalo, Roberto ; Brasier, Allan R. ; Casola, Antonella. / Ikkepsilon regulates viral-induced interferon regulatory factor-3 activation via a redox-sensitive pathway. In: Virology. 2006 ; Vol. 353, No. 1. pp. 155-165.
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