title: Specific Induction of TSLP by the Viral RNA Analogue Poly(I:C) in Primary Epithelial Cells Derived from Nasal Polyps.
abstract: BACKGROUND
  Chronic rhinosinusitis with nasal polyposis is an inflammatory disease that, although not directly linked to allergy, often displays a Th2-skewed inflammation characterized by elevated local IgE and IL-5 levels. The nasal cavity is constantly exposed to bacteria and viruses that may trigger epithelial inflammatory responses. To gain more insight into mechanisms by which such a biased inflammation might arise, we have investigated the epithelial expression of the Th2 skewing mediators (TSLP, IL-25, and IL-33) in relationship to disease and microbial triggers.
  
  
  METHODS
  Epithelial cells were obtained from polyp tissues of nasal polyposis patients and from inferior turbinates of non-diseased controls. Cells were exposed to various TLR-specific triggers to study the effect on mRNA and protein expression level of TSLP, IL-25, and IL-33 and the potential regulatory mechanisms through the expression profile the transcription factors ATF-3, DUSP-1, EGR-1, and NFKB-1.
  
  
  RESULTS
  The TLR3 agonist and viral analogue poly(I:C) induced TSLP mRNA 13.0 ± 3.1 fold (p < 0.05) and protein expression by 12.1 ± 2.3-fold (p < 0.05) higher in epithelium isolated from nasal polyposis patients than in epithelium form healthy controls. This enhanced induction of TSLP may be a consequence of a down-regulated expression of DUSP-1 in polyp epithelium.
  
  
  CONCLUSIONS
  The TLR3 induced expression of TSLP introduces a mechanism by which the Th2-skewed tissue environment might arise in nasal polyps and invites a further evaluation of the potential contribution of current or past viral infections to polyposis pathogenesis.
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Korneliusz
authors.initials: K
authors.lastname: Golebski
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Tongeren
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: van Egmond
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: de Groot
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Wytske J
authors.initials: WJ
authors.lastname: Fokkens
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Cornelis M
authors.initials: CM
authors.lastname: van Drunen
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology; D011070:Poly I-C / Q000378:metabolism*; D012367:RNA, Viral / Q000502:physiology*; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D011070:Poly I-C; D000094632:Thymic Stromal Lymphopoietin