LSC Abstract – Rhinovirus infection induces NRF2 in monocytes but not in epithelial cells, via distinct intracellular pathways

Rhinoviruses are a major driver of the reduced lung function seen during exacerbations in a number of airway diseases including asthma and COPD. Viral infection is associated with increased inflammation in the lungs and increased oxidative stress in the airways. Monocyte and epithelial cells lines (THP-1 and BEAS2B respectively) were infected with rhinovirus strain RV16. Infection of both cell lines resulted in increased inflammation however, the oxidative stress responses were different. Infection of epithelial cells resulted in increased intracellular ROS whereas infection of monocytes decreased intracellular ROS. Infected BEAS2B cells showed decreased antioxidant capacity compared to that seen in THP-1 cells. In particular, infection of THP-1 cells increased expression of the antioxidant geneNRF2and reduced NOS2 and NOS3 gene expression. Using a pharmacological approach we demonstrated that RV16-induced inflammation and NRF2 expression was ERK/JNK-dependent in THP-1 cells, whereas, RV16-induced inflammation in BEAS-2B cells was p38 MAPK- and NF-κB-dependent. Whilst both monocytes and epithelial cells show similar RV-16-induced inflammatory responses, these cells show different oxidative stress responses to infection and the responses to infection are driven by distinct intracellular signalling pathways.