title: Modeling the airway epithelium in allergic asthma: interleukin-13- induced effects in differentiated murine tracheal epithelial cells.
abstract: Mucous cells of the airway epithelium play a crucial role in the pathogenesis of human inflammatory airway diseases. Therefore, it is of importance to complement in vivo studies that use murine models of allergic asthma with in vitro mechanistic studies that use murine airway epithelial cells, including mucus-containing cells. In this study, we report the development and characterization of an in vitro culture system for primary murine tracheal epithelial (MTE) cells comprising ciliated cells and a substantial number of mucous cells. The increase in mucous cell number over that observed in the native murine airway, or in previously described murine cultures, creates a culture intermediate between the in vivo murine airway epithelium and in vitro cultures of human airway epithelial cells. To establish the usefulness of this culture system for the study of epithelial effects during inflammatory airway diseases, the cells were exposed to interleukin (IL)-13, a central inflammatory mediator in allergic asthma. The IL-13 induced two characteristic epithelial effects, proliferation and modulation of MUC5AC gene expression. There was a concentration dependence of these events, wherein high concentrations of IL-13 (10 ng/ml) induced proliferation, whereas lower concentrations (1 ng/ml) increased MUC5AC mRNA (where mRNA is messenger RNA). Interestingly, these effects occurred in an inverse manner, with the high concentration of IL-13 also provoking a significant decrease in MUC5AC gene expression. Thus, MTE cells cultured in this manner may provide an important link between experimental findings from animal models of allergic asthma and their application to human disease.
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lankford
authors.forename: Mariangela
authors.initials: M
authors.lastname: Macchione
authors.forename: Anne L
authors.initials: AL
authors.lastname: Crews
authors.forename: Shaun A
authors.initials: SA
authors.lastname: McKane
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Akley
authors.forename: Linda D
authors.initials: LD
authors.lastname: Martin
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology* / Q000276:immunology; D014132:Trachea / Q000033:anatomy & histology
chemical_list: D018793:Interleukin-13; C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins