TY - JOUR
T1 - Phenotypic and physiologic variability in nasal epithelium cultured from smokers and non-smokers exposed to secondhand tobacco smoke
AU - Carson, Johnny L.
AU - Lu, Tsui Shan
AU - Brighton, Luisa
AU - Hazucha, Milan
AU - Jaspers, Ilona
AU - Zhou, Haibo
N1 - Funding Information:
Acknowledgments This study was supported by a Clinical Innovator Award to JLC from the Flight Attendant Medical Research Institute, Grant #R01CA79949 from the National Institutes of Health to HZ, and the US Environmental Protection Agency. Although the research described in this article has been funded wholly or in part by the US Environmental Protection Agency through cooperative agreement CR833463-01 with the Center for Environmental Medicine, Asthma, and Lung Biology at the University of North Carolina at Chapel Hill, it has not been subjected to the agency’s required peer and policy review, and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
PY - 2010/7
Y1 - 2010/7
N2 - The emergence of air-liquid interface (ALI) culturing of mammalian airway epithelium is a recent innovation for experimental modeling of airway epithelial development, function, and pathogenic mechanisms associated with infectious agent and irritant exposure. This construct provides an experimental platform for in vitro propagation, manipulation, and testing of airway epithelium in a structural and physiologic state that emulates in vivo organization. In this study, we have cultured nasal epithelial biopsies from human subjects with variable histories of tobacco smoke exposure and assessed ciliary beat frequency (CBF) after an extended interval in vitro relative to CBF determined on biopsies from the same subjects immediately upon acquisition. We observed elevated CBF in nasal epithelial biopsies as well as persistence of accelerated CBF in ALI cultures deriving from biopsies of smokers and non-smokers exposed to environmental tobacco smoke compared to CBF in cultures from biopsies of well-documented non-smokers. Moreover, cultures deriving from smokers exhibited reduced ciliation as the cultures matured. These studies document that nasal epithelium cultured in the ALI system retains physiologic and phenotypic characteristics of the epithelial layer in vivo even through rounds of proliferative expansion. These observations suggest that stable epigenetic factors affecting regulation of ciliary function and phenotype commitment may be operative.
AB - The emergence of air-liquid interface (ALI) culturing of mammalian airway epithelium is a recent innovation for experimental modeling of airway epithelial development, function, and pathogenic mechanisms associated with infectious agent and irritant exposure. This construct provides an experimental platform for in vitro propagation, manipulation, and testing of airway epithelium in a structural and physiologic state that emulates in vivo organization. In this study, we have cultured nasal epithelial biopsies from human subjects with variable histories of tobacco smoke exposure and assessed ciliary beat frequency (CBF) after an extended interval in vitro relative to CBF determined on biopsies from the same subjects immediately upon acquisition. We observed elevated CBF in nasal epithelial biopsies as well as persistence of accelerated CBF in ALI cultures deriving from biopsies of smokers and non-smokers exposed to environmental tobacco smoke compared to CBF in cultures from biopsies of well-documented non-smokers. Moreover, cultures deriving from smokers exhibited reduced ciliation as the cultures matured. These studies document that nasal epithelium cultured in the ALI system retains physiologic and phenotypic characteristics of the epithelial layer in vivo even through rounds of proliferative expansion. These observations suggest that stable epigenetic factors affecting regulation of ciliary function and phenotype commitment may be operative.
KW - Cell culture
KW - Cilia
KW - Epithelium
KW - Inhalation toxicology
KW - Tobacco smoke
UR - http://www.scopus.com/inward/record.url?scp=77955426491&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77955426491&partnerID=8YFLogxK
U2 - 10.1007/s11626-010-9310-6
DO - 10.1007/s11626-010-9310-6
M3 - Article
C2 - 20383665
AN - SCOPUS:77955426491
SN - 1071-2690
VL - 46
SP - 606
EP - 612
JO - In Vitro Cellular and Developmental Biology - Animal
JF - In Vitro Cellular and Developmental Biology - Animal
IS - 7
ER -