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Characterization of Ciliated Bronchial Epithelium 1, a Ciliated Cell–Associated Gene Induced During Mucociliary Differentiation

Infection, Inflammation, and Repair and Human Genetics Divisions, University of Southampton School of Medicine, Southampton General Hospital, Southampton, United Kingdom; and Pharmacia Corporation, Kalamazoo, Michigan

Address correspondence to: Hajime Yoshisue, Ph.D., Infection, Inflammation, and Repair Division, University of Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. E-mail: hyoshisu{at}soton.ac.uk

Lung epithelial structure is altered in asthma; however, the precise mechanisms underlying epithelial repair, including differentiation from basal to columnar epithelial cells, are not well defined. In the course of random sequencing of a cDNA library from human lung biopsies, we have identified a novel gene, ciliated bronchial epithelium 1 (CBE1). Expression of CBE1 was induced during in vitro differentiation of bronchial epithelial cells. Synchronous expression with tektin and hepatocyte nuclear factor 3/forkhead homologue 4, down-regulation by interleukin-13, and its tissue distribution strongly suggested that CBE1 is associated with ciliated cells. Two isoforms of the 0.7-kb full-length cDNA were identified, resulting in open reading frames with different carboxyl termini, with no homology to known proteins. Expression of CBE1 in ciliated epithelial cells was confirmed by immunohistochemistry. Quantitative reverse transcription–polymerase chain reaction analysis using bronchial biopsies showed no difference of expression of CBE1 between normal subjects and subjects with asthma. Expression studies showed that CBE1 is nuclear- or perinuclear-localized, depending on cell type. Regulated expression during differentiation and the subcellular localization of CBE1 suggest that it may play an important role in the differentiation and/or function of ciliated cells in human airways.

Abbreviations: air–liquid interface, ALI • bovine serum albumin, BSA • ciliated bronchial epithelium, CBE • axonemal dynein intermediate-chain gene 1, DNAI1 • enhanced green fluorescent protein, EGFP • fluorescein isothiocyanate, FITC • hepatocyte nuclear factor 3/forkhead homologue 4, FOXJ1 • human bronchial epithelial, HBE • immunohistochemistry, IHC • interleukin, IL • open reading frame, ORF • phosphate-buffered saline, PBS • primary cilia dyskinesia, PCD • polymerase chain reaction, PCR • quantitative PCR, qPCR • rapid amplification of cDNA ends, RACE • reverse transcription PCR, RT-PCR • saline sodium citrate, SSC • T helper type 2, Th2

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