title: Th2 cytokines associated with chronic rhinosinusitis with polyps down-regulate the antimicrobial immune function of human sinonasal epithelial cells.
abstract: BACKGROUND
  Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a disorder characterized by persistent eosinophilic Th2 inflammation and frequent sinonasal microbial colonization. It has been postulated that an abnormal mucosal immune response underlies disease pathogenesis. The relationship between Th2 inflammatory cytokines and the innate immune function of sinonasal epithelial cells (SNECs) has not been explored.
  
  
  METHODS
  Human SNECs (HSNECs) isolated from control subjects and patients with CRS were assessed for expression of antimicrobial innate immune genes and proinflammatory cytokine genes by real-time polymerase chain reaction, ELISA, and flow cytometry. A model of the Th2 inflammatory environment was created by exposure of primary HSNEC to the Th2 cytokine interleukin (IL)-4 or IL-13 for 36 hours, with subsequent assessment of innate immune gene expression.
  
  
  RESULTS
  HSNEC obtained from CRSwNP patients displayed decreased expression of multiple antimicrobial innate immune markers, including toll-like receptor 9, human beta-defensin 2, and surfactant protein A. Baseline expression of these genes by normal and CRS HSNEC in culture is significantly down-regulated after incubation with IL-4 or IL-13.
  
  
  CONCLUSIONS
  Expression of multiple innate immune genes by HSNEC is reduced in CRSwNP. One mechanism appears to be a direct effect of the leukocyte-derived Th2 cytokines present in the sinonasal mucosa in CRSwNP. Impaired mucosal innate immunity may contribute to microbial colonization and abnormal immune responses associated with CRSwNP.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21287-0910, USA.
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Lee
authors.forename: Ernst W
authors.initials: EW
authors.lastname: Spannhake
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
mesh_terms: D016022:Case-Control Studies; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D018928:Immunity, Mucosal; D018793:Interleukin-13; D015847:Interleukin-4; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism; D009298:Nasal Polyps / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D051217:Toll-Like Receptor 9; D023083:beta-Defensins
chemical_list: D016207:Cytokines; D018793:Interleukin-13; D037662:Pulmonary Surfactant-Associated Protein A; D051217:Toll-Like Receptor 9; D023083:beta-Defensins; D015847:Interleukin-4