Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects

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

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Background: Excessive oxidative stress has been reported to be generated in inflamed tissues and contribute to the pathogenesis of inflammatory lung diseases, exacerbations of which induced by viral infections are associated with toll-like receptor (TLR) activation. Among these receptors, TLR8 has been reported as a key receptor that recognizes single-strand RNA virus. However, it remains unknown whether TLR8 signaling is potentiated by oxidative stress. The aim of this study is to examine whether oxidative stress modulates TLR8 signaling in vitro.Methods: Human peripheral blood neutrophils were obtained from healthy non-smokers and stimulated with TLR 7/8 agonist imidazoquinoline resiquimod (R848) in the presence or absence of hydrogen peroxide (H2O2). Neutrophilic responses including cytokine release, superoxide production and chemotaxis were examined, and the signal transduction was also analyzed.Results: Activation of TLR8, but not TLR7, augmented IL-8 release. The R848-augmented IL-8 release was significantly potentiated by pretreatment with H2O2 (p < 0.01), and N-acetyl-L-cysteine reversed this potentiation. The combination of H2O2 and R848 significantly potentiated NF-kB phosphorylation and IkBα degradation. The H2O2-potentiated IL-8 release was suppressed by MG-132, a proteosome inhibitor, and by dexamethasone. The expressions of TLR8, myeloid differentiation primary response gene 88 (MyD88), and tumor necrosis factor receptor-associated factor 6 (TRAF6) were not affected by H2O2.Conclusion: TLR8-mediated neutrophilic responses were markedly potentiated by oxidative stress, and the potentiation was mediated by enhanced NF-kB activation. These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection.

Original languageEnglish
Article number50
JournalRespiratory Research
Publication statusPublished - 2009 Jun 15


Dive into the research topics of 'Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects'. Together they form a unique fingerprint.

Cite this