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

Authors
 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 
Citation
 ANTIOXIDANTS & REDOX SIGNALING, Vol.16(1) : 57-70, 2012 
Journal Title
 ANTIOXIDANTS & REDOX SIGNALING 
ISSN
 1523-0864 
Issue Date
2012
MeSH
Animals ; Calcium/metabolism ; Cluster Analysis ; Cytosol/metabolism ; Dual Oxidases ; Epithelial Cells/metabolism ; Flagellin/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation/immunology ; Inflammation/metabolism* ; Interleukin-8/immunology ; Interleukin-8/metabolism ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mucin 5AC/immunology ; Mucin 5AC/metabolism ; Mutation ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism* ; Nasal Lavage Fluid/immunology ; Neutrophil Infiltration/immunology ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/immunology ; Respiratory Mucosa/metabolism* ; Toll-Like Receptor 5/immunology ; Toll-Like Receptor 5/metabolism*
Keywords
Animals ; Calcium/metabolism ; Cluster Analysis ; Cytosol/metabolism ; Dual Oxidases ; Epithelial Cells/metabolism ; Flagellin/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Inflammation/immunology ; Inflammation/metabolism* ; Interleukin-8/immunology ; Interleukin-8/metabolism ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Mucin 5AC/immunology ; Mucin 5AC/metabolism ; Mutation ; NADPH Oxidases/genetics ; NADPH Oxidases/metabolism* ; Nasal Lavage Fluid/immunology ; Neutrophil Infiltration/immunology ; Reactive Oxygen Species/metabolism ; Respiratory Mucosa/immunology ; Respiratory Mucosa/metabolism* ; Toll-Like Receptor 5/immunology ; Toll-Like Receptor 5/metabolism*
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-2? production upon challenging flagellin. INNOVATION: Our observation in this study reveals that flagellin-induced hydrogen peroxide (H(2)O(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(2)O(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.
Full Text
http://online.liebertpub.com/doi/abs/10.1089/ars.2011.3898
DOI
21714724
Appears in Collections:
5. Research Institutes (연구소) > Research Center for Human Natural Defense System (생체방어연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Hoon(김창훈) ORCID logo https://orcid.org/0000-0003-1238-6396
Ryu, Ji Hwan(유지환)
Yoon, Joo Heon(윤주헌)
Lee, Sang Nam(이상남)
Joo, Jung Hee(주정희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/89580
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