Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa

Jung Hee Joo, Ji Hwan Ryu, Chang Hoon Kim, Hyun Jik Kim, Mi Sun Suh, Jin Oh Kim, Seung Yeun Chung, Sang Nam Lee, Hwan Mook Kim, Yun Soo Bae, Joo Heon Yoon

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Abstract

Aims: Airway mucosa is constantly exposed to various airborne microbes, and epithelial host defense requires a robust innate immunity. Recently, it has been suggested that NADPH oxidase (NOX) isozymes serve functional roles in toll-like receptor (TLR)-mediated innate immune responses. However, the molecular mechanism between TLR and NOX-mediated reactive oxygen species (ROS) production in human airway mucosa has been poorly understood. Results: Here, we show that flagellin-induced ROS generation is dependent on dual oxidase 2 (DUOX2) activation, which is regulated by [Ca 2+] i mobilization in primary normal human nasal epithelial (NHNE) cells. Interestingly, we observed that silencing of DUOX2 expression in NHNE cells and nasal epithelium of Duox2 knockout mice failed to trigger mucin and MIP-2α production upon challenging flagellin. Innovation: Our observation in this study reveals that flagellin-induced hydrogen peroxide (H 2O 2) generation is critical for TLR5-dependent innate immune responses, including IL-8 production and MUC5AC expression in the nasal epithelium. Furthermore, DUOX2-mediated H 2O 2 generation activated by the flagellin-TLR5 axis might serve as a novel therapeutic target for infectious inflammation diseases in the airway tract. Conclusion: Taken together, we propose that DUOX2 plays pivotal roles in TLR5-dependent inflammatory response of nasal airway epithelium.

Original languageEnglish
Pages (from-to)57-70
Number of pages14
JournalAntioxidants and Redox Signaling
Volume16
Issue number1
DOIs
Publication statusPublished - 2012 Jan 1

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Joo, J. H., Ryu, J. H., Kim, C. H., Kim, H. J., Suh, M. S., Kim, J. O., Chung, S. Y., Lee, S. N., Kim, H. M., Bae, Y. S., & Yoon, J. H. (2012). Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. Antioxidants and Redox Signaling, 16(1), 57-70. https://doi.org/10.1089/ars.2011.3898