title: Timothy grass pollen extract-induced gene expression and signalling pathways in airway epithelial cells.
abstract: BACKGROUND
  Grass pollen allergy is one of the most common allergies worldwide and airborne allergens are the major cause of allergic rhinitis. Airway epithelial cells (AECs) are the first to encounter and respond to aeroallergens and are therefore interesting targets for the development of new therapeutics. Our understanding of the epithelial contribution to immune responses is limited as most studies focus on only a few individual genes or proteins.
  
  
  OBJECTIVE
  To describe in detail the Timothy grass pollen extract (GPE)-induced gene expression in AECs.
  
  
  METHODS
  NCI-H292 cells were exposed to GPE for 24 h, and isolated RNA and cell culture supernatants were used for microarray analysis and multiplex ELISA, respectively.
  
  
  RESULTS
  Eleven thousand and seven hundred fifty-eight transcripts were affected after exposure to GPE, with 141 genes up-regulated and 121 genes down-regulated by more than threefold. The gene ontology group cell communication was among the most prominent categories. Network analysis revealed that a substantial part of regulated genes are related to the cytokines IL-6, IL-8, IL-1A, and the transcription factor FOS. After analysing significantly regulated signalling pathways, we found, among others, epidermal growth factor receptor 1, IL-1, Notch-, and Wnt-related signalling members. Unexpectedly, we found Jagged to be down-regulated and an increased release of IL-12, in line with a more Th1-biased response induced by GPE.
  
  
  CONCLUSIONS
  Our data show that the stimulation of AECs with GPE results in the induction of a broad response on RNA and protein level by which they are able to affect the initiation and regulation of local immune responses. Detailed understanding of GPE-induced genes and signalling pathways will allow us to better define the pathogenesis of the allergic response and to identify new targets for treatment.
authors.affiliation: Department of Otorhinolaryngology, Academic Medical Center, Amsterdam, The Netherlands. K.I.Roschmann@amc.uva.nl
authors.forename: K I L
authors.initials: KI
authors.lastname: Röschmann
authors.forename: S
authors.initials: S
authors.lastname: Luiten
authors.forename: M J
authors.initials: MJ
authors.lastname: Jonker
authors.forename: T M
authors.initials: TM
authors.lastname: Breit
authors.forename: W J
authors.initials: WJ
authors.lastname: Fokkens
authors.forename: A
authors.initials: A
authors.lastname: Petersen
authors.forename: C M
authors.initials: CM
authors.lastname: van Drunen
mesh_terms: D000485:Allergens / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D031784:Phleum / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D015203:Reproducibility of Results; D020545:Respiratory Mucosa / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines