Cigarette Smoke Modulates Repair and Innate Immunity following Injury to Airway Epithelial Cells

• Published in: PloS one 2016-11, Vol.11 (11), p.e0166255-e0166255
• Main Authors: Amatngalim, Gimano D, Broekman, Winifred, Daniel, Nadia M, van der Vlugt, Luciën E P M, van Schadewijk, Annemarie, Taube, Christian, Hiemstra, Pieter S
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Blotting, Western; Bronchi - cytology; Bronchi - drug effects; Cell adhesion & migration; Cells, Cultured; Chronic obstructive lung disease; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Epidermal growth factor; Epithelial cells; Humans; Immune response; Immunity; Immunity, Innate - drug effects; Inflammation; Injuries; Innate immunity; Integrity; Lung cancer; Lung diseases; MAP Kinase Signaling System - physiology; Medicine and Health Sciences; Microscopy, Fluorescence; Mucous membrane; Obstructive lung disease; Oxidative stress; Oxidative Stress - drug effects; Pathogens; Real-Time Polymerase Chain Reaction; Receptor, Epidermal Growth Factor - physiology; Repair; Respiratory Mucosa - drug effects; Respiratory Mucosa - immunology; Respiratory tract; Ribonuclease; Ribonuclease 7; Ribonucleases - metabolism; Risk factors; Rodents; Signal transduction; Signal Transduction - physiology; Smoke; Smoking; Smoking - adverse effects; Wound care; Wound healing; Wound Healing - drug effects; Wounding
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0166255

Cigarette smoking is the main risk factor associated with chronic obstructive pulmonary disease (COPD), and contributes to COPD development and progression by causing epithelial injury and inflammation. Whereas it is known that cigarette smoke (CS) may affect the innate immune function of airway epithelial cells and epithelial repair, this has so far not been explored in an integrated design using mucociliary differentiated airway epithelial cells. In this study, we examined the effect of whole CS exposure on wound repair and the innate immune activity of mucociliary differentiated primary bronchial epithelial cells, upon injury induced by disruption of epithelial barrier integrity or by mechanical wounding. Upon mechanical injury CS caused a delayed recovery in the epithelial barrier integrity and wound closure. Furthermore CS enhanced innate immune responses, as demonstrated by increased expression of the antimicrobial protein RNase 7. These differential effects on epithelial repair and innate immunity were both mediated by CS-induced oxidative stress. Overall, our findings demonstrate modulation of wound repair and innate immune responses of injured airway epithelial cells that may contribute to COPD development and progression.