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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 \u03bcM H2O2 significantly potentiated the release of IL-8 from the epithelial cells after stimulation with 10 \u03bcg\/ml poly(I:C). The H2O2-augmented IL-8 release was inhibited by treatment with N-acetylcysteine. One hundred micromoles of H2O2 enhanced the translocation of nuclear factor (NF)-\u03baB p65, but not that of interferon regulatory factor-3 (IRF-3), into the nucleus and the NF-\u03baB 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-\u03baB 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.<\/jats:p>","DOI":"10.1165\/rcmb.2008-0345oc","type":"journal-article","created":{"date-parts":[[2009,7,13]],"date-time":"2009-07-13T21:52:56Z","timestamp":1247521976000},"page":"651-660","source":"Crossref","is-referenced-by-count":50,"title":["Oxidative Stress Enhances Toll-Like Receptor 3 Response to Double-Stranded RNA in Airway Epithelial Cells"],"prefix":"10.1093","volume":"42","author":[{"given":"Akira","family":"Koarai","sequence":"first","affiliation":[{"name":"Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisatoshi","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, Wakayama, 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