Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:119

Article

Dharajiya, Nilesh ; Choudhury, Barun K. ; Bacsi, Attila ; Boldogh, Istvan ; Alam, Rafeul ; Sur, Sanjiv

关键词: allergy;    inflammation;    antioxidants;    eosinophils;    T(H)2;   

DOI  :  10.1016/j.jaci.2006.11.634

来源: Elsevier

【 摘 要 】

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 I 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-hydroxymmenal 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. Conclusion: Signal I plays a proinflammatory role during repeated exposure to pollen extract. We propose that inhibiting signal I by increasing antioxidant potential in the airways may be a novel therapeutic strategy to attenuate pollen-induced allergic airway inflammation. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.

【 授权许可】

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