title: Signal transduction and oxidative processes in sinonasal polyposis.
abstract: BACKGROUND
  Nasal polyposis is characterized by impaired regulation of nasal tissue growth and is associated with chronic inflammation, sinus infections, and low levels of nitric oxide (NO). Based on its critical role in mediating cell growth and antimicrobial function, decrease of NO levels has been implicated in the pathogenesis of nasal polyposis.
  
  
  OBJECTIVE
  We sought to evaluate mechanisms for the low NO level in polyposis, including factors regulating NO synthase (NOS) expression and activity and NO consumptive processes in nasal epithelial cells and nasal lavage fluid.
  
  
  METHODS
  Eighteen patients with nasal polyposis and 8 healthy control subjects were studied. Nasal brushings, nasal lavage fluid, and nasal biopsy specimens were collected and analyzed.
  
  
  RESULTS
  NO metabolite levels (nitrite and nitrate) in nasal lavage fluid from patients with polyps were less than those in control subjects, but activation of signal transduction and inducer of transcription 1, which regulates inducible NOS gene expression and protein expression, was present at higher levels in polyp than in healthy control tissue. Levels of arginine, methylarginine, and endogenous NOS inhibitors were similar between polyp and control tissue. In contrast, superoxide dismutase activity of polyp tissues was lower than that seen in control tissue and associated with increased nitrotyrosine, a biomarker of oxidant consumptive products of NO.
  
  
  CONCLUSIONS
  Taken together, these data suggest that the nasal polyp environment is characterized by abnormalities in NO metabolism that might predispose to altered regulation of tissue growth and infection.
  
  
  CONCLUSIONS
  Identification of NO metabolic abnormalities might lead to novel treatments for sinonasal polyposis targeted against the pathways identified within this study.
authors.affiliation: Head and Neck Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA. cannads@ccf.org
authors.forename: Steven B
authors.initials: SB
authors.lastname: Cannady
authors.forename: Pete S
authors.initials: PS
authors.lastname: Batra
authors.forename: Rachel
authors.initials: R
authors.lastname: Leahy
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Citardi
authors.forename: Allison
authors.initials: A
authors.lastname: Janocha
authors.forename: Kristin
authors.initials: K
authors.lastname: Ricci
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Melanie
authors.initials: M
authors.lastname: Bodine
authors.forename: Zeneng
authors.initials: Z
authors.lastname: Wang
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000328:Adult; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D009298:Nasal Polyps / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D050794:STAT1 Transcription Factor / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013379:Substrate Specificity; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase