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Timothy grass pollen extract‐induced gene expression and signalling pathways in airway epithelial cells
Author(s) -
Röschmann K I. L.,
Luiten S.,
Jonker M. J.,
Breit T. M.,
Fokkens W. J.,
Petersen A.,
van Drunen C. M.
Publication year - 2011
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2011.03713.x
Subject(s) - biology , gene , gene expression , immune system , airborne allergen , wnt signaling pathway , allergy , transcription factor , microarray , microarray analysis techniques , immunology , microbiology and biotechnology , genetics , allergen
Cite this as : K. I. L. Röschmann, S. Luiten, M. J. Jonker, T. M. Breit, W. J. Fokkens, A. Petersen and C. M. van Drunen, Clinical & Experimental Allergy , 2011 (41) 830–841. Summary 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. Conclusion and Clinical Relevance 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.