Altered mitochondrial reactive oxygen species (ROS) production in airway smooth muscle cells of severe asthma

Abstract

Introduction: Increased airway smooth muscle cell (ASMC) mass is a feature of airway remodelling is correlated with asthma severity. Glucocorticoids (GCs) fail to suppress this component of the disease. GCs act via both nuclear and mitochondrial pathways. Dysfunctional mitochondria have been implicated in asthma; the precise GC-mitochondrial interactions, and the influence of disease severity on these, remain poorly understood. Hypothesis: There is altered mitochondrial activity in cultured ASMCs from patients with severe asthma (SA) compared to non-severe asthma (NSA) which is differentially regulated by GCs. Methods: Primary ASMCs were isolated from bronchial biopsy samples of SA and NSA patients. Mitochondrial activity was assessed in serum-starved ASMCs over a 24 hour period through measurements of mitochondrial membrane potential (ΔΨm) by JC-1 staining and ROS production by MitoSOX Red staining, both at baseline and in response to dexamethasone (Dex). Results: Mitochondrial ROS production was enhanced at baseline in SA vs NSA ASMCs under conditions of serum-starvation (p Conclusions: Cultured SA ASMCs show different levels of mitochondrial ROS ROS production compared to NSA ASMCs both at baseline and in response to the GCs, alluding to altered mitochondrial responses between asthma groups. Funding: Sanming Project of Medicine in Shenzhen (SZSM201612096).