Cigarette Smoke Modulates Repair and Innate Immunity following Injury to Airway Epithelial Cells.
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.
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Gimano D
GD
Amatngalim
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Winifred
W
Broekman
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Nadia M
NM
Daniel
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Luciën E P M
LE
van der Vlugt
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Annemarie
A
van Schadewijk
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Christian
C
Taube
Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
Pieter S
PS
Hiemstra
D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000276:immunology; D012260:Ribonucleases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012907:Smoking / Q000009:adverse effects*; D014945:Wound Healing / Q000187:drug effects
D066246:ErbB Receptors; D012260:Ribonucleases; C470000:Ribonuclease 7