Oxidative stress enhances toll-like receptor 3 response to double-stranded RNA in airway epithelial cells

Akira Koarai, Hisatoshi Sugiura, Satoru Yanagisawa, Tomohiro Ichikawa, Yoshiaki Minakata, Kazuto Matsunaga, Tsunahiko Hirano, Keiichiro Akamatsu, Masakazu Ichinose

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50 Citations (Scopus)


Virus infections are a major cause of chronic obstructive pulmonary disease (COPD) exacerbations. Recently, Toll-like receptor 3 (TLR3) has been demonstrated to react to double-stranded RNA (dsRNA) and to be involved in the immune responses after viral infections. In the present study, we examined whether oxidative stress, which is involved in the pathogenesis of COPD, enhances the responses of TLR3 in airway epithelial cells. The effect of hydrogen peroxide (H2O2) on the release of IL-8 from BEAS-2B cells and primary human bronchial epithelial cells after stimulation with polyinosine-polycytidylic acid [poly(I:C)], a synthetic analog of viral dsRNA and a ligand for TLR3, and the signal transduction were examined. One hundred to 150 μM H2O2 significantly potentiated the release of IL-8 from the epithelial cells after stimulation with 10 μg/ml poly(I:C). The H2O2-augmented IL-8 release was inhibited by treatment with N-acetylcysteine. One hundred micromoles of H 2O2 enhanced the translocation of nuclear factor (NF)-κB p65, but not that of interferon regulatory factor-3 (IRF-3), into the nucleus and the NF-κB DNA binding activity after poly(I:C) stimulation, which effect was inhibited not by the silencing of IRF-3 but by MG132, a proteasome inhibitor, or dexamethasone. One hundred micromoles of H2O2 potentiated the TLR3 expression on the airway epithelial cells treated with poly(I:C). These data suggest that oxidative stress augments the response of TLR3 in airway epithelial cells via NF-κB and that this effect might be partly mediated by the enhancement of TLR3 expression. Modulation of this pathway may be a therapeutic target for viral-induced exacerbations of COPD.

Original languageEnglish
Pages (from-to)651-660
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number6
Publication statusPublished - 2010 Jun 1


  • Chronic obstructive pulmonary disease
  • Exacerbation
  • Hydrogen peroxide
  • Nuclear factor-κB


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