title: Synergy between TLR-2 and TLR-3 signaling in primary human nasal epithelial cells.
abstract: BACKGROUND
  Although we have a detailed understanding of how single microbial derived triggers activate specialized Toll-like receptors (TLR) on airway epithelial cells, we know little of how these receptors react in a more complex environment. In everyday life, nasal epithelial cells are exposed to multiple TLR agonists, therefore we explored whether exposure to one trigger could affect the responsiveness to another TLR trigger.
  
  
  METHODS
  Primary nasal epithelium from healthy individuals and the bronchial epithelium cell line NCI-H292 were exposed in vitro to different TLR specific agonists. The effect on the expression of different TLRs was determined using the q-PCR. We also evaluated the effect of TLR-3 stimulation on TLR-2, functionally using ELISA to determine levels of secreted mediators.
  
  
  RESULTS
  Stimulation of airway epithelial cells with a specific TLR agonist affects gene expression of other TLRs. In primary nasal epithelium, poly(I:C) challenge results in an up-regulation of the TLR-1, TLR-2, and TLR-3 genes and reduction of expression of TLR-5. Poly(I:C) induced activation of TLR-2 contributes to stronger cell responses to a TLR-2 agonist and regulation of these synergistic responses may take place at the mRNA level of IL-6 and IL-8. The effect of TLR-3 stimulation on TLR-2 functionality and most of the effects on the expression of other TLRs could be replicated in NCI-H292. Poly(I:C) failed to up-regulate TLR-1 and showed an additional up-regulation of TLR-4.
  
  
  CONCLUSIONS
  Our data suggest that to better understand TLR mediated innate responses we need to consider the impact of the presence of multiple triggers.
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: van Tongeren
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands. Electronic address: k.golebski@amc.uva.nl.
authors.forename: Korneliusz
authors.initials: K
authors.lastname: Golebski
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: Danielle
authors.initials: D
authors.lastname: Van Egmond
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: Esther J
authors.initials: EJ
authors.lastname: de Groot
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: Wytske J
authors.initials: WJ
authors.lastname: Fokkens
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
authors.forename: Cornelis M
authors.initials: CM
authors.lastname: van Drunen
mesh_terms: D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D009297:Nasal Mucosa / Q000378:metabolism*; D011070:Poly I-C / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008024:Ligands; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D011070:Poly I-C
keywords: Nasal epithelium; Poly(I:C); Synergy; TLR-2; TLR-3