title: Nitric oxide regulation of asthmatic airway inflammation with segmental allergen challenge.
abstract: BACKGROUND
  Despite evidence of increased nitric oxide (NO) in asthmatic compared with healthy individuals, the role of NO in airway inflammation is unclear.
  
  
  OBJECTIVE
  The purpose of the study was to determine the in vivo effects of localized allergen challenge on airway NO levels and transcription factor activation.
  
  
  METHODS
  In this study localized allergen challenge was used as a model of asthmatic exacerbation to determine the relationship of NO to airway inflammation.
  
  
  RESULTS
  With allergen challenge, asthmatic patients had a rise in airway NO levels, whereas NO levels in healthy controls did not change. The increased NO in asthma with allergen challenge compared with healthy control subjects was associated with an increase in inflammatory cytokines (GM-CSF and macrophage inflammatory protein-1) in epithelial lining fluid and eosinophilic infiltrate in bronchoalveolar lavage fluid (BAL) and biopsy specimens. To investigate the mechanisms of cytokine gene expression, activation of the transcription factors activator protein-1 and nuclear factor-kappaB (NF-kappaB) in cells from BAL were evaluated. Activator protein-1 was not activated before or after local allergen challenge. In contrast, NF-kappaB activation was less in BAL cells from asthmatic patients with increased NO in comparison with controls.
  
  
  CONCLUSIONS
  Our studies are the first to suggest an inverse correlation between NF-kappaB and airway NO in a localized segmental allergen challenge model in allergic asthmatic patients. The current study demonstrates that activation of the inflammatory response (eg, cytokines, cellular infiltrate) in allergic asthmatic patients is temporally associated with increased airway NO. We propose that NO that is up-regulated by cytokines is part of an autoregulatory feedback loop (ie, allergen challenge stimulates inflammatory cytokine production, which in turn stimulates NO production, and NO down-regulates cytokine production).
authors.affiliation: Departments of Pulmonary and Critical Care Medicine, Cell Biology, Pathology, Neurosciences, Biostatistics, and Cancer Biology, Cleveland Clinic Foundation, Cleveland, OH 44195-5038, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Thomassen
authors.forename: B
authors.initials: B
authors.lastname: Raychaudhuri
authors.forename: R A
authors.initials: RA
authors.lastname: Dweik
authors.forename: C
authors.initials: C
authors.lastname: Farver
authors.forename: L
authors.initials: L
authors.lastname: Buhrow
authors.forename: A
authors.initials: A
authors.lastname: Malur
authors.forename: M J
authors.initials: MJ
authors.lastname: Connors
authors.forename: J
authors.initials: J
authors.lastname: Drazba
authors.forename: J
authors.initials: J
authors.lastname: Hammel
authors.forename: S C
authors.initials: SC
authors.lastname: Erzurum
authors.forename: M S
authors.initials: MS
authors.lastname: Kavuru
mesh_terms: D000328:Adult; D000485:Allergens / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054407:Chemokine CCL4; D016207:Cytokines / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007958:Leukocyte Count / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000494:pharmacology; D014157:Transcription Factors / Q000494:pharmacology
chemical_list: D000485:Allergens; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D009569:Nitric Oxide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor