title: DUOX-Mediated Signaling Is Not Required for LPS-Induced Neutrophilic Response in the Airways.
abstract: Oxidant production from DUOX1 has been proposed to lead to neutrophil recruitment into the airways when lung homeostasis is compromised. The objective of this study was to determine whether DUOX-derived hydrogen peroxide is required for LPS-induced neutrophil recruitment, using a functional DUOX knock out mouse model. We found that LPS induced profound neutrophilic lung inflammation in both Duoxa(+/+)and Duoxa(-/-) mice between 3h and 24h. Duoxa(-/-) mice had significantly higher neutrophil influx 24h after LPS instillation despite similar cytokine levels (KC, MIP-2, or TGF-α) between the two groups. These findings suggest that LPS-TLR-4-induced KC or MIP-2 cytokine induction and subsequent neutrophil recruitment in the airway does not require DUOX-derived hydrogen peroxide from airway epithelium.
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Linderholm
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, School of Medicine, University of California at Davis, Davis, California 95616, United States.
authors.forename: Richart
authors.initials: R
authors.lastname: Harper
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D000074623:Dual Oxidases; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000502:physiology*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C519130:Duox1 protein, mouse