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Original Research: COPD |

Bronchial Airway Epithelial Cell Damage Following Exposure to Cigarette Smoke Includes Disassembly of Tight Junction Components Mediated by the Extracellular Signal-Regulated Kinase 1/2 Pathway

Loredana Petecchia, PhD; Federica Sabatini, PhD; Luigi Varesio, PhD; Anna Camoirano, BS; Cesare Usai, PhD; Annalisa Pezzolo, PhD; Giovanni A. Rossi, MD
Author and Funding Information

*From the Pulmonary Disease Unit (Drs. Petecchia, Sabatini, and Rossi), Molecular Biology Laboratory (Dr. Varesio), and Oncology and Pathology Laboratory (Dr. Pezzolo), G. Gaslini Institute, Genoa, Italy; the Department of Health Sciences (Ms. Camoirano), University of Genoa, Genoa, Italy; and Institute of Biophysics (Dr. Usai), National Research Council, Genoa, Italy.

Correspondence to: Loredana Petecchia, PhD, Pulmonary Diseases Unit G, Gaslini Institute, Largo G. Gaslini 5, 16147 Genoa, Italy; e-mail: loredanapetecchia@ospedale-gaslini.ge.it


This study was supported by Grant “Ricerca Corrente” from Italian Ministry of Health, Rome, Italy. The work was performed in the Pulmonary Disease Unit, G. Gaslini Institute, Genoa, Italy.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(6):1502-1512. doi:10.1378/chest.08-1780
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Background:  Through a variety of biochemical mechanisms, cigarette smoke (CS) may damage airway epithelium, altering its normal structure and function. Injury to epithelium may include changes in tight junction (TJ) integrity with impairment of epithelial barrier function.

Methods and results:  To study the effect of the exposure to CS condensate (CSC) on TJ integrity, two human bronchial epithelial cell lines (HBECs), BEAS-2B and 16HBE14o-, were used. Exposure of the two HBECs to CSC resulted in a time-dependent and concentration-dependent disassembly of TJs, which were already detectable at 24 h at all the CSC concentrations tested (5%, 10%, and 20%), associated with changes in cell shape, suggesting cell damage. However, a significant inhibition of cell growth and an increase in DNA fragmentation were detected only at the highest CSC concentration tested (20%) at 48 and 72 h, respectively. The involvement of epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase (ERK) 1/2 cascade in CSC-induced damage was shown by the observation that exposure to CSC (5%) induced a marked phosphorylation of ERK1/2, already detectable after 5-min incubation and confirmed by the demonstration that not only ERK1/2 phosphorylation but also CSC-induced TJ disassembly and DNA fragmentation were partially inhibited by a mitogen-activated protein kinase kinase inhibitor (U0126) and completely blocked by a EGFR inhibitor (AG1478).

Conclusion:  CSC-induced damage to airway epithelium includes disassembly of TJs, modulated through the EGFR-ERK1/2 signaling pathway.

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