title: A 3-D well-differentiated model of pediatric bronchial epithelium demonstrates unstimulated morphological differences between asthmatic and nonasthmatic cells.
abstract: There is a need for reproducible and effective models of pediatric bronchial epithelium to study disease states such as asthma. We aimed to develop, characterize, and differentiate an effective, an efficient, and a reliable three-dimensional model of pediatric bronchial epithelium to test the hypothesis that children with asthma differ in their epithelial morphologic phenotype when compared with nonasthmatic children. Primary cell cultures from both asthmatic and nonasthmatic children were grown and differentiated at the air-liquid interface for 28 d. Tight junction formation, MUC5AC secretion, IL-8, IL-6, prostaglandin E2 production, and the percentage of goblet and ciliated cells in culture were assessed. Well-differentiated, multilayered, columnar epithelium containing both ciliated and goblet cells from asthmatic and nonasthmatic subjects were generated. All cultures demonstrated tight junction formation at the apical surface and exhibited mucus production and secretion. Asthmatic and nonasthmatic cultures secreted similar quantities of IL-8, IL-6, and prostaglandin E2. Cultures developed from asthmatic children contained considerably more goblet cells and fewer ciliated cells compared with those from nonasthmatic children. A well-differentiated model of pediatric epithelium has been developed that will be useful for more in vivo like study of the mechanisms at play during asthma.
authors.affiliation: Centre for Infection and Immunity and School of Medicine, Queen's University Belfast, Belfast, BT12 6BN, Northern Ireland.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Parker
authors.forename: Severine
authors.initials: S
authors.lastname: Sarlang
authors.forename: Surendran
authors.initials: S
authors.lastname: Thavagnanam
authors.forename: Grace
authors.initials: G
authors.lastname: Williamson
authors.forename: Dara
authors.initials: D
authors.lastname: O'donoghue
authors.forename: Remi
authors.initials: R
authors.lastname: Villenave
authors.forename: Ultan
authors.initials: U
authors.lastname: Power
authors.forename: Michael
authors.initials: M
authors.lastname: Shields
authors.forename: Liam
authors.initials: L
authors.lastname: Heaney
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Skibinski
mesh_terms: D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D002648:Child; D015232:Dinoprostone / Q000096:biosynthesis; D004848:Epithelium / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008954:Models, Biological; D055271:Mucin 5AC / Q000378:metabolism; D019108:Tight Junctions
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D015232:Dinoprostone