Abstract
Background: Asthma has been associated with an increase in reactive oxidant species(ROS) in the airways. ROS are known to affect mitochondrial function and this may impact on bronchial epithelial cell responses, including antiviral responses to rhinovirus(RV) infection.
AIM: To compare mitochondrial function and antiviral responses in primary bronchial epithelial cells(pBECs) to RV infection from asthmatics and healthy controls(HC).
METHODS: pBECs from asthmatics and healthy subjects were infected with RV at an MOI of 1 and were then treated with 1% CSE and 0.2mM H2O2. CXCL10, CXCL8, interferon (IFN)- λ, cytochrome c and 8-isoprostane were measured by ELISA. ATP levels were measured by bioluminescent assay. Mitochondrial transcription factors (mTFA, mTB1 and mTB2) were measured by RT-PCR. Viral replication was measured by TCID50.
RESULTS: Treatment with CSE and H2O2 resulted in ROS-induced mitochondrial damage; with increased expression of mitochondrial transcription factors, release of cytochrome-C and 8-isoprostane which were more significant in asthmatics. Treatment with CSE/H2O2 followed by RV infection further increased mTFA expression, extracellular ATP and cytochrome-C release in asthmatics. Also in asthmatics, there was a marked reduction in antiviral responses; CXCL-10 and IFN- λ release, but there was an increase in CXCL8 release. In the case of CSE and H2O2, there was an increase in RV replication which was only seen in asthmatics.
CONCLUSION: Asthmatic pBECs are more sensitive to the effects of ROS, demonstrating an impaired mitochondrial response, and leading to impaired antiviral response to RV infection.
- © 2014 ERS