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CHARACTERIZATION OF INFLAMMATORY MEDIATOR RELEASE FROM AN IN VITRO HUMAN TRACHEAL/BRONCHIAL EPITHELIAL TISSUE MODEL.

Hayden, P., Jackson, R., Last, T.J., Klausner, M. and Kubilus, J. MatTek Corp., Ashland, MA 01721.
Abstract

Monolayer cultures of human-derived tracheal/bronchial epithelial (TBE) cells have been instrumental in understanding the mechanisms of respiratory tract pathologies such as cystic fibrosis, asthma, and tracheal and bronchial inflammation. However, cells in monolayer culture lack the differentiated function of normal in vivo tissue. For instance, monolayer cells are not polarized, they lack cilia and tight junctions, and they do not produce mucin, all of which are characteristic of the epithelial cells of the trachea and bronchus. To overcome these shortcomings, three-dimensional differentiated models of the airway epithelium have been investigated and considerable progress has been achieved in reproducing normal airway epithelial physiology. It may also be expected that expression of secreted cytokines, chemokines and lipid derived inflammatory mediators change during differentiation of tracheal/bronchial cells. For example, Eling et al have shown that undifferentiated TBE cells express high levels of prostaglandin-H synthase and little or no lipoxygenase enzymes, while the reverse is found in fully differentiated TBE tissues in vitro. The purpose of the current studies is to further characterize EpiAirway™, a fully differentiated TBE tissue with regard to the expression of a variety of chemokines and lipid mediators which are thought to play important roles in airway inflammatory processes. 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-1b, TNF-a or the TH2 cytokines IL-4 or IL-13.

Keywords

3-Dimensional (3-D), Asthma, Bronchial, Bronchial epithelial, Bronchial inflammation, COX-1, COX-2, Chemokines, Cilia, Cyclooxygenase, Cyclooxygenase-1, Cyclooxygenase-2 , Cystic fibrosis, Cytokines, Eotaxin, EpiAirway, GM-CSF, Gene expression, IL-13, IL-1b, IL-4, Inflammation, Inflammatory, Inflammatory mediator release, Lipoxygenase, Monolayer culture, Mucin, Mucin secretion, Mucociliary, NHBE, Normal airway epithelial physiology, Prostaglandin – H, Rantes, Respiratory, TBE, TNF-a, Tight junctions, Tracheal, Tracheal bronchial epithelial (TBE), Tracheal inflammation

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