Barrier function of airway tract epithelium

Ganesan, Shyamala; Comstock, Adam T; Sajjan, Uma S

However, our studies have not shown binding of RV to tight junction proteins. Instead, RV-induced barrier dysfunction is dependent on ROS generation. 93, 111 Oxidative stress constitutes a well-studied mechanism of tight junction breakdown, inducing tyrosine phosphorylation and dissociation of occludin from the tight junction complex. 113 Our on-going studies indicate that while normal differentiated airway epithelial cell cultures show restoration of barrier function at 4 d post-RV infection, similarly differentiated COPD cell cultures show barrier dysfunction up to 14 d after RV infection (Faris and Sajjan, unpublished results). Based on these preliminary observations, we speculate that RV infection in COPD patients may further damage airway epithelium, and this may in turn promote airway remodeling, increase the risk for acquiring secondary infections and alter innate immune responses to infection or other environmental insults ultimately leading to progression of lung disease. Therefore, strategies to inhibit barrier disruption or quickly restore barrier function after viral infection may prevent progression of lung disease in patients with COPD and possibly in subjects with other chronic airways disease such as cystic fibrosis and asthma.