Development of cystic fibrosis and noncystic fibrosis airway cell lines.
In this study, we utilized the reverse transcriptase component of telomerase, hTERT, and human papillomavirus type 16 (HPV-16) E6 and E7 genes to transform normal and cystic fibrosis (CF) human airway epithelial (HAE) cells. One cell line, designated NuLi-1 (normal lung, University of Iowa), was derived from HAE of normal genotype; three cell lines, designated CuFi (cystic fibrosis, University of Iowa)-1, CuFi-3, and CuFi-4, were derived from HAE of various CF genotypes. When grown at the air-liquid interface, the cell lines were capable of forming polarized differentiated epithelia that exhibited transepithelial resistance and maintained the ion channel physiology expected for the genotypes. The CF transmembrane conductance regulator defect in the CuFi cell lines could be corrected by infecting from the basolateral surface using adenoviral vectors. Using nuclear factor-kappaB promoter reporter constructs, we also demonstrated that the NuLi and CuFi cell lines retained nuclear factor-kappaB responses to lipopolysaccharide. These cell lines should therefore be useful as models for studying ion physiology, therapeutic intervention for CF, and innate immunity.
Zabner
Joseph
J
Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA. joseph-zabner@uiowa.edu
Karp
Phil
P
Seiler
Michael
M
Phillips
Stacia L
SL
Mitchell
Calista J
CJ
Saavedra
Mimi
M
Welsh
Michael
M
Klingelhutz
Aloysius J
AJ
D000256:Adenoviridae / Q000235:genetics; D018929:Cell Culture Techniques / Q000379:methods*; D002461:Cell Line, Transformed; D016764:Cell Polarity; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005355:Fibrosis; D005822:Genetic Vectors; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics; D010641:Phenotype; D020545:Respiratory Mucosa / Q000166:cytology*; D012190:Retroviridae / Q000235:genetics; D012964:Sodium / Q000378:metabolism
C505032:CFTR protein, human; D002712:Chlorides; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012964:Sodium