title: Nicotinic acetylcholine receptor expression in human airway correlates with lung function.
abstract: Nicotine and its derivatives, by binding to nicotinic acetylcholine receptors (nAChRs) on bronchial epithelial cells, can regulate cellular signaling and inflammatory processes. Delineation of nAChR subtypes and their responses to nicotine stimulation in bronchial epithelium may provide information for therapeutic targeting in smoking-related inflammation in the airway. Expression of nAChR subunit genes in 60 bronchial epithelial biopsies and immunohistochemical staining for the subcellular locations of nAChR subunit expression were evaluated. Seven human bronchial epithelial cell lines (HBECs) were exposed to nicotine in vitro for their response in nAChR subunit gene expression to nicotine exposure and removal. The relative normalized amount of expression of nAChR α4, α5, and α7 and immunohistochemical staining intensity of nAChR α4, α5, and β3 expression showed significant correlation with lung function parameters. Nicotine stimulation in HBECs resulted in transient increase in the levels of nAChR α5 and α6 but more sustained increase in nAChR α7 expression. nAChR expression in bronchial epithelium was found to correlate with lung function. Nicotine exposure in HBECs resulted in both short and longer term responses in nAChR subunit gene expression. These results gave insight into the potential of targeting nAChRs for therapy in smoking-related inflammation in the airway.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China; dcllam@hku.hk.
authors.forename: David Chi-Leung
authors.identifier: http://orcid.org/0000-0002-0004-2660
authors.initials: DC
authors.lastname: Lam
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China;
authors.forename: Susan Yang
authors.initials: SY
authors.lastname: Luo
authors.affiliation: Department of Pathology, Tseung Kwan O Hospital, Hong Kong, China;
authors.forename: Kin-Hang
authors.initials: KH
authors.lastname: Fu
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China;
authors.forename: Macy Mei-Sze
authors.initials: MM
authors.lastname: Lui
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China;
authors.forename: Koon-Ho
authors.initials: KH
authors.lastname: Chan
authors.affiliation: Department of Translational Molecular Pathology, MD Anderson Cancer Center, Houston, Texas;
authors.forename: Ignacio Ivans
authors.initials: II
authors.lastname: Wistuba
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; and.
authors.forename: Boning
authors.initials: B
authors.lastname: Gao
authors.affiliation: Cell Signalling and Integrative Biology Research Cluster, School of Biomedical Sciences, University of Hong Kong, Hong Kong, China.
authors.forename: Sai-Wah
authors.initials: SW
authors.lastname: Tsao
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, China;
authors.forename: Mary Sau-Man
authors.initials: MS
authors.lastname: Ip
authors.affiliation: Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas; and.
authors.forename: John Dorrance
authors.initials: JD
authors.lastname: Minna
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena / Q000235:genetics; D012907:Smoking / Q000378:metabolism
chemical_list: D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: bronchial epithelium; lung function; nicotine; nicotinic acetylcholine receptor; quantitative polymerase chain reaction