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Schamberger, A.C. ; Mise, N. ; Jia, J. ; Genoyer, E. ; Yildirim, A.Ö. ; Meiners, S. ; Eickelberg, O.

Cigarette smoke-induced disruption of bronchial epithelial tight junctions is prevented by transforming growth factor-beta.

Am. J. Respir. Cell Mol. Biol. 50, 1040-1052 (2014)
Postprint Manuscript DOI PMC
Open Access Green
The airway epithelium constitutes an essential immunological and cytoprotective barrier to inhaled insults, such as cigarette smoke, environmental particles, or viruses. While bronchial epithelial integrity is crucial for airway homeostasis, defective epithelial barrier function contributes to chronic obstructive pulmonary disease (COPD). Tight junctions at the apical side of epithelial cell-cell contacts determine epithelial permeability. Cigarette smoke exposure, the major risk factor for COPD, is suggested to impair tight junction integrity; however, detailed mechanisms thereof remain elusive. Here, we investigated whether cigarette smoke extract (CSE) and transforming growth factor (TGF)-β1 affected tight junction integrity. Exposure of human bronchial epithelial cells (16HBE14o-), as well as differentiated primary human bronchial epithelial cells (pHBECs), to CSE significantly disrupted tight junction integrity and barrier function. Specifically, CSE decreased transepithelial electrical resistance (TEER) and tight junction-associated protein levels. Zona occludens (ZO)-1 and -2 protein levels were significantly reduced and dislocated from the cell membrane, as observed by fractionation and immunofluorescence analysis. These findings were reproduced in isolated bronchi exposed to CSE ex vivo, as detected by qRT-PCR and immunohistochemistry. Importantly, combined treatment of 16HBE14o- cells or pHBECs with CSE and TGF-β1 restored ZO-1 and ZO-2 protein levels. TGF-β1 co-treatment restored not only membrane localization of ZO-1 and ZO-2 protein, but also prevented CSE-mediated TEER decrease. In conclusion, CSE led to the disruption of tight junctions of human bronchial epithelial cells, while TGF-β1 counteracted this CSE-induced effect. Thus, TGF-β1 may serve as a protective factor for bronchial epithelial cell homeostasis in diseases such as COPD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Zonula Occludens ; Airway Epithelium ; Chronic Obstructive Pulmonary Disease ; Ciliated Cell; Obstructive Pulmonary-disease; Barrier Function; Guinea-pigs; Respiratory Epithelium; Increased Permeability; Airway Epithelium; In-vitro; Cells; Lung; Proteasome
ISSN (print) / ISBN 1044-1549
e-ISSN 1535-4989
Zeitschrift American Journal of Respiratory Cell and Molecular Biology
Quellenangaben Band: 50, Heft: 6, Seiten: 1040-1052 Artikelnummer: , Supplement: ,
Verlag American Thoracic Society
Verlagsort New York
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)