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

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

Research output: Contribution to journalArticle

50 Citations (Scopus)

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. Conclusion: 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. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.

Original languageEnglish (US)
Pages (from-to)646-653
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number3
DOIs
StatePublished - Mar 2007

Fingerprint

Ambrosia
Pollen
NADP
Oxidoreductases
Antioxidants
Inflammation
NADPH Oxidase
Reactive Oxygen Species
Ascorbic Acid
Tocopherols
Mucins
Interleukin-4
Epithelial Cells
Lung
Chloride Channels
Interleukin-13
Adaptive Immunity
Eosinophils
Cultured Cells
Oxidative Stress

Keywords

  • Allergy
  • antioxidants
  • eosinophils
  • inflammation
  • T2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation. / Dharajiya, Nilesh; Choudhury, Barun; Bacsi, Attila; Boldogh, Istvan; Alam, Rafeul; Sur, Sanjiv.

In: Journal of Allergy and Clinical Immunology, Vol. 119, No. 3, 03.2007, p. 646-653.

Research output: Contribution to journalArticle

@article{d4e2de5b1d0a49d6afa3c40ced1fe76c,
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. Conclusion: 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. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.",
keywords = "Allergy, antioxidants, eosinophils, inflammation, T2",
author = "Nilesh Dharajiya and Barun Choudhury and Attila Bacsi and Istvan Boldogh and Rafeul Alam and Sanjiv Sur",
year = "2007",
month = "3",
doi = "10.1016/j.jaci.2006.11.634",
language = "English (US)",
volume = "119",
pages = "646--653",
journal = "Journal of Allergy and Clinical Immunology",
issn = "0091-6749",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Inhibiting pollen reduced nicotinamide adenine dinucleotide phosphate oxidase-induced signal by intrapulmonary administration of antioxidants blocks allergic airway inflammation

AU - Dharajiya, Nilesh

AU - Choudhury, Barun

AU - Bacsi, Attila

AU - Boldogh, Istvan

AU - Alam, Rafeul

AU - Sur, Sanjiv

PY - 2007/3

Y1 - 2007/3

N2 - 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. Conclusion: 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. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.

AB - 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. Conclusion: 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. Clinical implications: Administration of antioxidants in the airways may constitute a novel therapeutic strategy to prevent pollen induced allergic airway inflammation.

KW - Allergy

KW - antioxidants

KW - eosinophils

KW - inflammation

KW - T2

UR - http://www.scopus.com/inward/record.url?scp=33847346503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847346503&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2006.11.634

DO - 10.1016/j.jaci.2006.11.634

M3 - Article

VL - 119

SP - 646

EP - 653

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 3

ER -