title: Gene expression differences in nitric oxide and reactive oxygen species regulation point to an altered innate immune response in chronic rhinosinusitis.
abstract: BACKGROUND
  The complex interplay between host, environment, and microbe in the etiopathogenesis of chronic rhinosinusitis (CRS) remains unclear. This study focuses on the host-microbe interaction, specifically the regulation of nitric oxide (NO) and reactive oxygen species (ROS) against the pathogenic organism Staphylococcus aureus (S. aureus). NO and ROS play crucial roles in innate immunity and in the first-line defense against microbial invasion.
  
  
  METHODS
  Sinonasal tissue samples were harvested from CRS and control patients during surgery. CRS patients were classified S. aureus biofilm-positive (B+) or biofilm-negative (B-) using fluorescence in situ hybridization and clinically as polyp-positive (P+) or polyp-negative (P-). Samples were assessed using an NO polymerase chain reaction (PCR) array containing 84 genes involved in NO and ROS regulation, and gene expression of all subgroups were compared to each other.
  
  
  RESULTS
  Twenty-three samples were analyzed with 31 genes significantly changed, the greatest seen in the B+P+ CRS patients. Four genes consistently displayed differential expression between the groups including the cytoprotective oxidation resistance 1 (OXR1) and peroxiredoxin 6 (PRDX6), neutrophil cytosolic factor 2 (NCF2), and the prion protein (PRNP) genes.
  
  
  CONCLUSIONS
  Alteration in gene expression points to impaired innate immune responses differing among CRS subgroups based on S. aureus biofilm and polyp status. The consistent alteration of 4 genes among distinct groups demonstrates that S. aureus biofilms and polyps are associated with specific changes in gene expression. Further studies are required to validate these findings in a wider cohort of patients and correlate this to protein expression and disease manifestation.
authors.affiliation: Department of Surgery, Otorhinolaryngology-Head and Neck Surgery, The Queen Elizabeth Hospital and the University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Camille
authors.initials: C
authors.lastname: Jardeleza
authors.forename: Damien
authors.initials: D
authors.lastname: Jones
authors.forename: Leonie
authors.initials: L
authors.lastname: Baker
authors.forename: Dijana
authors.initials: D
authors.lastname: Miljkovic
authors.forename: Samuel
authors.initials: S
authors.lastname: Boase
authors.forename: Neil Cheng-Wen
authors.initials: NC
authors.lastname: Tan
authors.forename: Sarah
authors.initials: S
authors.lastname: Vreugde
authors.forename: Lor Wai
authors.initials: LW
authors.lastname: Tan
authors.forename: Peter-John
authors.initials: PJ
authors.lastname: Wormald
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018441:Biofilms / Q000254:growth & development; D002908:Chronic Disease; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D024101:Mitochondrial Proteins; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009298:Nasal Polyps / Q000150:complications / Q000235:genetics* / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D010256:Paranasal Sinuses / Q000276:immunology* / Q000382:microbiology; D054465:Peroxiredoxin VI / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012220:Rhinitis / Q000150:complications / Q000235:genetics* / Q000276:immunology; D012852:Sinusitis / Q000150:complications / Q000235:genetics* / Q000276:immunology; D013203:Staphylococcal Infections / Q000150:complications / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D055815:Young Adult
chemical_list: D024101:Mitochondrial Proteins; C419777:OXR1 protein, human; D011328:Prions; D011506:Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D054465:Peroxiredoxin VI; D019255:NADPH Oxidases; C527764:NCF2 protein, human