title: Human upper airway epithelium produces nitric oxide in response to Staphylococcus epidermidis.
abstract: Nitric oxide (NO) is produced by sinonasal epithelial cells as part of the innate immune response against bacteria. We previously described bitter-taste-receptor-dependent and -independent NO responses to product(s) secreted by Pseudomonas aeruginosa and Staphylococcus aureus, respectively. We hypothesized that sinonasal epithelium would be able to detect the gram-positive, coagulase-negative bacteria Staphylococcus epidermidis and mount a similar NO response.
  
  
  
  Sinonasal air-liquid interface cultures were treated with conditioned medium (CM) from lab strains and clinical isolates of coagulase-negative staphylococci and S aureus. NO production was quantified by fluorescence imaging. Bitter taste receptor signaling inhibitors were utilized to characterize the pathway responsible for NO production in response to S epidermidis CM.
  
  
  
  S epidermidis CM contains a low-molecular-weight, heat, and protease-stabile product that induces an NO synthase (NOS)-mediated NO production that is less robust than the response triggered by S aureus CM. The S epidermidis CM-stimulated NO response is not inhibited by antagonists of phospholipase C isoform β-2 nor the transient receptor potential melastatin isoform 5 ion channel, both critical to bitter taste signaling.
  
  
  
  This study identifies an NO-mediated innate defense response in sinonasal epithelium elicited by S epidermidis product(s). The active bacterial product is likely a small, nonpeptide molecule that stimulates a pathway independent of bitter taste receptors. Although the NO response to S epidermidis is less vigorous compared with S aureus, the product(s) share similar characteristics. Together, the responses to staphylococci species may help explain the pathophysiology of upper respiratory infections.
authors: Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors: Ryan M
authors: RM
authors: Carey
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors: Bei
authors: B
authors: Chen
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors: Nithin D
authors: ND
authors: Adappa
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors: James N
authors: JN
authors: Palmer
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors: David W
authors: DW
authors: Kennedy
authors: Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA.
authors: Robert J
authors: RJ
authors: Lee
authors: 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: Noam A
authors: NA
authors: Cohen
mesh_terms: D006801:Humans; D007113:Immunity, Innate; D009297:Nasal Mucosa / Q000276:immunology*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus; D013212:Staphylococcus epidermidis
chemical_list: D009569:Nitric Oxide
keywords: S epidermidis; chronic rhinosinusitis; epithelial; infection, innate immunity; nitric oxide