Effect of oxidative stress and rhinovirus infection on mitochondrial/endoplasmic reticular function in human primary bronchial epithelial cells

Asthma is characterised by chronic airway inflammation and increased susceptibility to virus infections, such as Rhinovirus (RV), consequently the airway epithelium is exposed to high levels of oxidative stress. The Mitochondria play a central role in cellular metabolism and the immune response to virus infections. While mitochondrial dysfunction has been described in many chronic inflammatory diseases, little is known about its role in airway diseases. Here we assessed the impact of the exposure of cigarette smoke, hydrogen peroxide (H 2 O 2 ), tunicamycin (ER stress) and human rhinovirus infection (RV-1B) on mitochondrial function of human primary bronchial epithelial cells (pBECs) grown at the air liquid interface or submerged culture system. Mitochondrial functions were assessed by Seahorse XF e 96 analyser and measuring cytochrome-C release. Pro-inflammatory cytokines were measured to evaluate the level of inflammation. Infection with RV-1B demonstrated a reduced mitochondrial respiration and increased proton leak. This is accompanied with increased pro-inflammatory cytokines. Exposure of 1% CS increased the mitochondrial oxygen consumption rate, increased cytochrome-C release and increased virus replication compared with untreated cells. Induction of ER stress also increased the mitochondrial respiration. Exposure of 0.2mM H 2 O 2 completely arrested the mitochondrial respiration with or without infection. Taken together these results demonstrate that exposure of cigarette smoke or other forms of oxidative and ER stress change the mitochondrial function leading to impaired immune responses to RV.