Development of cystic fibrosis and noncystic fibrosis airway cell lines

Author:

Zabner Joseph1,Karp Phil1,Seiler Michael1,Phillips Stacia L.2,Mitchell Calista J.2,Saavedra Mimi3,Welsh Michael14,Klingelhutz Aloysius J.2

Affiliation:

1. Departments of Internal Medicine and

2. Microbiology,

3. Department of Internal Medicine, University of Colorado, Denver, Colorado 80262

4. Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242; and

Abstract

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-κB promoter reporter constructs, we also demonstrated that the NuLi and CuFi cell lines retained nuclear factor-κB responses to lipopolysaccharide. These cell lines should therefore be useful as models for studying ion physiology, therapeutic intervention for CF, and innate immunity.

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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