Quercetin Reduces Oxidative Stress of Cold Virus
Methods. Human bronchial airway (16HBE14o-) epithelial cells grown as polarized monolayers were infected apically with RV39. After 1 h, infection media was replaced with fresh media in the presence or absence of selected chemical inhibitors (see below), and incubated for an additional 23 h. TER was measured using a voltmeter. Tyrosine phosphorylation of ZO-1 and Rac1 activation were determined by pull-down assays.
Results. RV infection induced expression of NADPH oxidase (NOX)-1 and stimulated Rac1 and NADPH oxidase activity. Chemical inhibitors of NOX, diphenyleneiodonium (DPI), and Rac1, NSC23766 reversed RV-induced reductions in TER. Poly I:C treatment also reduced the TER and DPI reversed this effect. ROS scavenger, n-propylgallate; PI3-kinase inhibitor, LY294002; a plant flavonoid, quercetin which functions both as ROS scavenger and PI3-kinase inhibitor; MMP inhibitor, O-phenanthroline; EGFR inhibitor AG1458; and the Src tyrosine kinase inhibitor, PP2 also inhibited the RV-induced reduction in TER. Further, RV-infection caused tyrosine phosphorylation of ZO-1, which was inhibited by DPI and PP2. Conclusions. We conclude that activation of Rac-1 dependent NADPH oxidase is required for RV-induced tyrosine phosphorylation of ZO-1 and reduced barrier function. We speculate tha
t RV infection induces the activation of a Src/PI 3-kinase/Rac1 signaling complex, leading to the generation of reactive oxygen, tyrosine phosphorylation of ZO-1 and dissociation of ZO-1 from the tight junction complex.
A. Comstock, BS, A. Chattoraj, MS, S. Ganesan, PhD, S. Chattoraj, MS, M.B. Hershenson, MD, U. Sajjan, PhD
Oxidative Stress Induced by Rhinovirus Plays a Role in the Disruption of Epithelial Barrier Function
American Thoracic Society May 2010 annual International Conference in New Orleans.
Ann Arbor, MI/US