Effect of age, COPD severity and cigarette smoke exposure on bronchial epithelial barrier function

We investigated the effect of age, cigarette smoke and COPD severity on epithelial barrier function. Primary bronchial epithelial cells (PBECs) were obtained from bronchial brushings in 8 younger and 8 older never-smokers; 7 older ex-smokers without COPD 8 COPD GOLD (Global Initiative for Chronic Obstructive Lung Disease) I-III and 6 COPD GOLD IV patients, and cultured in the absence/presence of cigarette smoke extract (CSE). Epithelial barrier function was assessed by electric resistance sensing and expression of junctional and antioxidant genes/proteins quantified by qPCR/immunodetection. Epithelial barrier function was comparable between PBECs from younger and older never-smokers. PBECs from ex-smokers had significantly lower barrier function compared to never-smokers, with a further decrease in COPD GOLD IV. CSE decreased epithelial barrier function from which PBECs from never-smokers, but not ex-smokers with and without COPD, recovered. Restoration of barrier function was accompanied by increased expression of barrier and antioxidant genes. At baseline, PBECs from ex-smokers with and without COPD had higher expression of junctional and antioxidant genes compared to never smokers. However, exposure to CSE increased antioxidant ( SOD1-3, CAT) gene expression only in PBECs from never-smokers and ex-smokers without COPD. In conclusion, our data indicate that cigarette smoking and COPD severity are associated with reduced epithelial barrier function, which is potentially driven by an imbalance in the antioxidant response.