title: Dual oxidase 2 is essential for the toll-like receptor 5-mediated inflammatory response in airway mucosa.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Taken together, we propose that DUOX2 plays pivotal roles in TLR5-dependent inflammatory response of nasal airway epithelium.
authors.affiliation: Research Center for Natural Human Defense System, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Joo
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Ryu
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Hyun Jik
authors.initials: HJ
authors.lastname: Kim
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Suh
authors.forename: Jin-Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Seung Yeun
authors.initials: SY
authors.lastname: Chung
authors.forename: Sang Nam
authors.initials: SN
authors.lastname: Lee
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016000:Cluster Analysis; D003600:Cytosol / Q000378:metabolism; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000378:metabolism; D005408:Flagellin / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055271:Mucin 5AC / Q000276:immunology / Q000378:metabolism; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D017817:Nasal Lavage Fluid / Q000276:immunology; D020556:Neutrophil Infiltration / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000276:immunology / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D055271:Mucin 5AC; D017382:Reactive Oxygen Species; D051198:Toll-Like Receptor 5; D005408:Flagellin; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431515:DUOX2 protein, human; C519130:Duox1 protein, mouse; D002118:Calcium