Interleukin 1-Beta Potentially Contributes to Chronic Obstructive Pulmonary Disease Development by Inducing Reactive Oxygen Species Production in Neutrophils.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and excessive mucin production. Two major gel-forming mucins, MUC5AC and MUC5B, correlate with worsened disease progression and pulmonary function. In COPD, neutrophils are important players in chronic inflammation that contribute to tissue damage through releasing reactive oxygen species (ROS). IL-1β, a pro-inflammatory cytokine, plays various roles in COPD disease progression. It is known to recruit and activate neutrophils and is also known to induce mucin production in bronchial epithelium. This study aimed to investigate whether IL-1β induces ROS production in neutrophils and whether neutrophil-derived ROS drives mucin secretion in bronchial epithelial cells. HL-60-derived neutrophils were treated with IL-1β or vehicle and neutrophil ROS production was assessed through flow cytometry. Using a co-culture system, human bronchial epithelial cells were exposed to IL-1β-treated neutrophils, and MUC5AC and MUC5B levels on these cells were evaluated at RNA and protein levels through RT-qPCR, immunofluorescence, and ELISAs. IL-1β induced neutrophil ROS production. The elevated ROS production in neutrophils induced MUC5AC and MUC5B production at mRNA and protein levels in bronchial epithelial cells. Inhibition of ROS production in neutrophils using a NOX2 inhibitor reduced MUC5AC and MUC5B secretion in bronchial epithelial cells. IL-1β-induced neutrophil-derived ROS is a key driver of mucin hypersecretion in bronchial epithelial cells, potentially contributing to COPD disease progression. Trial registration: Not applicable.