Cutting edge: Apoptosis-regulating signal kinase 1 is required for reactive oxygen species-mediated activation of IFN regulatory factor 3 by lipopolysaccharide

Edward Chiang, Oanh Dang, Keith Anderson, Atsushi Matsuzawa, Hidenori Ichijo, Michael David

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

IFN regulatory factor (IRF) 3 participates in the transcriptional induction of IFN-α, IFN-β, and a subset of IFN-stimulated genes (ISGs) as a result of viral infection. In addition, bacterial cell wall components such as LPS activate IRF3 in a p38-dependent manner. In this study we show that IRF3-mediated ISG induction by LPS requires the production of reactive oxygen species (ROS) by the NADPH-dependent oxidase NOX4. Furthermore, we present evidence that LPS-mediated ROS production leads to activation of apoptosis-regulating-signal kinase (ASK) 1, a MAPK kinase kinase family member capable of activating the MAP kinase 6/p38 axis. ASK1 kinase activity proved essential for IRF3-mediated ISG induction by LPS. Thus, our results presented here suggest a novel role for ROS and ASK1 in the innate immune response as signaling intermediates in the IRF3 activation pathway.

Original languageEnglish
Pages (from-to)5720-5724
Number of pages5
JournalJournal of Immunology
Volume176
Issue number10
DOIs
Publication statusPublished - 2006 May 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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