title: Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation.
abstract: BACKGROUND
  Ragweed extract (RWE) contains NADPH oxidases that induce oxidative stress in the airways independent of adaptive immunity (signal 1) and augment antigen (signal 2)-induced allergic airway inflammation.
  
  
  OBJECTIVE
  To test whether inhibiting signal 1 by administering antioxidants inhibits allergic airway inflammation in mice.
  
  
  METHODS
  The ability of ascorbic acid (AA), N-acetyl cystenine (NAC), and tocopherol to scavenge pollen NADPH oxidase-generated reactive oxygen species (ROS) was measured. These antioxidants were administered locally to inhibit signal 1 in the airways of RWE-sensitized mice. Recruitment of inflammatory cells, mucin production, calcium-activated chloride channel 3, IL-4, and IL-13 mRNA expression was quantified in the lungs.
  
  
  RESULTS
  Antioxidants inhibited ROS generation by pollen NADPH oxidases and intracellular ROS generation in cultured epithelial cells. AA in combination with NAC or Tocopherol decreased RWE-induced ROS levels in cultured bronchial epithelial cells. Coadministration of antioxidants with RWE challenge inhibited 4-hydroxynonenal adduct formation, upregulation of Clca3 and IL-4 in lungs, mucin production, recruitment of eosinophils, and total inflammatory cells into the airways. Administration of antioxidants with a second RWE challenge also inhibited airway inflammation. However, administration of AA+NAC 4 or 24 hours after RWE challenge failed to inhibit allergic inflammation.
  
  
  CONCLUSIONS
  Signal 1 plays a proinflammatory role during repeated exposure to pollen extract. We propose that inhibiting signal 1 by increasing antioxidant potential in the airways may be a novel therapeutic strategy to attenuate pollen-induced allergic airway inflammation.
  
  
  CONCLUSIONS
  Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.
authors.affiliation: National Heart, Lung, and Blood Institute Proteomics Center, University of Texas Medical Branch, Division of Allergy and Immunology, Department of Internal Medicine, Galveston, Texas, USA.
authors.forename: Nilesh
authors.initials: N
authors.lastname: Dharajiya
authors.forename: Barun K
authors.initials: BK
authors.lastname: Choudhury
authors.forename: Attila
authors.initials: A
authors.lastname: Bacsi
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.forename: Rafeul
authors.initials: R
authors.lastname: Alam
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Sur
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage; D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D001205:Ascorbic Acid / Q000008:administration & dosage; D001991:Bronchitis / Q000517:prevention & control*; D018118:Chloride Channels / Q000032:analysis / Q000378:metabolism; D006967:Hypersensitivity / Q000517:prevention & control*; D018793:Interleukin-13 / Q000032:analysis / Q000378:metabolism; D015847:Interleukin-4 / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000737:chemistry / Q000276:immunology; D051379:Mice; D009077:Mucins / Q000032:analysis / Q000378:metabolism; D050896:Nitrate Reductase (NAD(P)H) / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010936:Plant Extracts / Q000633:toxicity; D011058:Pollen / Q000201:enzymology / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D024505:Tocopherols / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D018118:Chloride Channels; D018793:Interleukin-13; D009077:Mucins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D015847:Interleukin-4; D050896:Nitrate Reductase (NAD(P)H); D001205:Ascorbic Acid; D024505:Tocopherols; D000111:Acetylcysteine