Oxidative stress induces expression through mitochondrial damage-dependent STING signaling in human bronchial epithelial cells.

Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI-H292) and normal human bronchial epithelial cells were used to confirm expression levels by real-time PCR when stimulated with hydrogen peroxide (HO). transcriptional activity was increased and mitochondrial DNA was released into the cytosol by HO. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in transcriptional activity. Cyclic GMP-AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. HO-induced expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild-type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.