Up-regulation of paraoxonase 2 in human bronchial epitehlial cells

Background: Obese-asthmatics have worse asthma control and experience higher rates of healthcare utilization. Increasing body mass index in asthmatics has been associated with greater airway oxidative stress and dysfunctional mitochondria. The antioxidant protein paraoxonase 2(PON2) plays an important role in preventing mitochondrial-derived oxidative stress and could therfore have therapeutic potential in these patients. To test this hypothesis we compared levels of PON2 in bronchial epithelial cells of obese-asthmatics and controls and determined the effects of quercetin on PON2 expression and on preventing oxidative stress. Methods: Human bronchial epitheilal cells were obtained from bronchoscopic brushings of obese-asthmatics and control subjects. PON2 were analyzed by western blot and densitometry performed for quantification. To test whether quercetin protects from oxidative stress we exposed those cells to two well-known oxidants; hydrogen peroxide and 1-2 naphthoquinone. After that mitochondrial superoxide and total hydrogen peroxide production were measured. Result: Primary human airway epithelial cells from obese-asthmatics have lower PON2 levels compared to controls. We found in in vitro culture that cells previously treated by quercetin significantly increased PON2 protein levels compared to controls and produced significanlty lower levels of hydrogen peroxide and mitochondrial ROS after the oxidant challengue. Conclusion: Increase in ROS production and mitochondrial dysfunction have been reported in obese and asthmatics; hence increasing PON2 protein levels through quercetin supplementation could be a potential therapeutic strategy to prevent obesity-mediated airway oxidative stress in obese-asthmatics.