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CHARACTERIZATION OF INFLAMMATORY MEDIATOR RELEASE FROM AN IN VITRO HUMAN BRONCHIAL/TRACHEAL EPITHELIAL TISSUE MODEL. Hayden, P., Jackson, R., Klausner, M., Kubilus, J. MatTek Corp., Ashland, MA. Presented at the Lovelace Respiratory Research Institute International Symposium, Santa Fe, NM, October 3, (2000).

Summary: Inflammatory mediator release from airway epithelium is believed to play a significant role in human disease states such as asthma and airway hypersensitivity reactions. In vitro models of differentiated bronchial/tracheal epithelial tissue have been increasingly helpful in elucidation of the specific role of the epithelium with regard to these and other diseases of the proximal airways. In the present work, EpiAirway™, an in vitro model of human bronchial/tracheal epithelial tissue which expresses a fully differentiated mucociliary phenotype, has been characterized with regard to the release of the chemokines RANTES, GM-CSF and eotaxin, and various cyclo-oxygenase and lipoxygenase products after exposure to IL-1β, TNF-α or the TH2 cytokines IL-4 or IL-13. EpiAirway tissues were treated with the various cytokines for 24 hours prior to EIA analysis for mediator release into the medium. IL-1β induced the strongest release of GM-CSF and RANTES, and slight increases in 12-HETE and 15-HETE, while TNF-α induced a weak release of GM-CSF and RANTES, 12-HETE and 15-HETE. IL-4 or IL-13 exposure resulted in increased production of 12-HETE and 15-HETE. Surprisingly, no eotaxin protein secretion was detected under any of the experimental conditions. None of the cytokine treatments caused a significant increase in the cyclo-oxygenase product PGE-2 or the 5-lipoxygenase product LTB4. These and further characterizations should allow differentiated human bronchial/tracheal tissues to make continuing contributions to our understanding of human airway diseases.

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Applications: Asthma, Characterization study, Inflammation - airway

Keywords: 12-HETE, 12-Hydroxy, 15-HETE, 15-Hydroxy, Chemokines, Eicosatetraenoic acid, Eotaxin, EpiAirway, GM-CSF, Human NHBE, Human airway diseases, IL-1b, IL-4, Inflammation, Inflammatory, Inflammatory mediator, Inflammatory mediator release, LTB, Lipoxygenase, NHBE, Pre-validation, Prevalidation, Rantes, TH2 cytokines, TNF-a, Validation



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