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

Research output: Contribution to journalArticle

43 Citations (Scopus)

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

Fingerprint

Toll-Like Receptor 5
Flagellin
Nasal Mucosa
Oxidoreductases
Mucous Membrane
Innate Immunity
NADPH Oxidase
Toll-Like Receptors
Nose
Reactive Oxygen Species
Mucin-2
Epithelial Cells
Mucins
Interleukin-8
Knockout Mice
Hydrogen Peroxide
Isoenzymes
Communicable Diseases
Innovation
Chemical activation

All Science Journal Classification (ASJC) codes

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

Cite this

Joo, Jung Hee ; Ryu, Ji Hwan ; Kim, Chang-Hoon ; Kim, Hyun Jik ; Suh, Mi Sun ; Kim, Jin Oh ; Chung, Seung Yeun ; Lee, Sang Nam ; Kim, Hwan Mook ; Bae, Yun Soo ; Yoon, Joo Heon. / Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. In: Antioxidants and Redox Signaling. 2012 ; Vol. 16, No. 1. pp. 57-70.
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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.",
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Joo, JH, Ryu, JH, Kim, C-H, Kim, HJ, Suh, MS, Kim, JO, Chung, SY, Lee, SN, Kim, HM, Bae, YS & Yoon, JH 2012, 'Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa', Antioxidants and Redox Signaling, vol. 16, no. 1, pp. 57-70. https://doi.org/10.1089/ars.2011.3898

Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa. / Joo, Jung Hee; Ryu, Ji Hwan; Kim, Chang-Hoon; Kim, Hyun Jik; Suh, Mi Sun; Kim, Jin Oh; Chung, Seung Yeun; Lee, Sang Nam; Kim, Hwan Mook; Bae, Yun Soo; Yoon, Joo Heon.

In: Antioxidants and Redox Signaling, Vol. 16, No. 1, 01.01.2012, p. 57-70.

Research output: Contribution to journalArticle

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AU - Joo, Jung Hee

AU - Ryu, Ji Hwan

AU - Kim, Chang-Hoon

AU - Kim, Hyun Jik

AU - Suh, Mi Sun

AU - Kim, Jin Oh

AU - Chung, Seung Yeun

AU - Lee, Sang Nam

AU - Kim, Hwan Mook

AU - Bae, Yun Soo

AU - Yoon, Joo Heon

PY - 2012/1/1

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N2 - 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.

AB - 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.

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