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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 DOI
Open Access Green
as soon as is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Keywords 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
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