title: Staphylococcus aureus triggers nitric oxide production in human upper airway epithelium.
abstract: BACKGROUND
  Nitric oxide (NO) is an important antibacterial defense molecule produced by upper airway (sinonasal) epithelial cells. We previously showed that a bitter taste receptor expressed in airway epithelium detects quorum-sensing molecules secreted by Gram-negative bacteria and subsequently triggers bactericidal NO production. We hypothesized that the upper airway epithelium may also be able to detect the Gram-positive aerobe Staphylococcus aureus and mount an NO response.
  
  
  METHODS
  Human sinonasal air-liquid interface (ALI) cultures were treated with methicillin-resistant S. aureus (MRSA)-conditioned medium (CM), and NO production was measured using fluorescence imaging. Inhibitors of bitter taste receptor signaling were used to pharmacologically determine if this pathway was involved in the production of NO.
  
  
  RESULTS
  A low-molecular-weight, heat, and protease-stabile product found in MRSA CM induced differential, NO synthase (NOS)-mediated NO production. This response varied markedly between individual patients. The MRSA-stimulated NO production was not dependent on 2 important components of bitter taste signaling: phospholipase C isoform β-2 or the transient receptor potential melastatin isoform 5 (TRPM5) ion channel.
  
  
  CONCLUSIONS
  This study shows that a S. aureus product elicits an NO-mediated innate defense response in human upper airway epithelium. The active bacterial product is likely a small, nonpeptide molecule that triggers a pathway independent of bitter taste receptors. Patient variation in the NO response to MRSA product(s), potentially due to genetic differences, might play a role in pathophysiology of Gram-positive upper respiratory infections and/or pathogenesis of chronic rhinosinusitis.
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Carey
authors.affiliation: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Workman
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: Bei
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: Nithin D
authors.initials: ND
authors.lastname: Adappa
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: James N
authors.initials: JN
authors.lastname: Palmer
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: David W
authors.initials: DW
authors.lastname: Kennedy
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.|Philadelphia Veterans Administration Medical Center Surgical Services, Philadelphia, PA.
authors.forename: Noam A
authors.initials: NA
authors.lastname: Cohen
mesh_terms: D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000276:immunology / Q000378:metabolism*; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D009569:Nitric Oxide
keywords: Staphylococcus aureus; chronic rhinosinusitis; epithelial; infection; innate immunity; nitric oxide