Neutrophil elastase increases MUC5AC mRNA and protein expression in respiratory epithelial cells

Chronic neutrophil-predominant inflammation and hypersecretion of mucus are common pathophysiological features of cystic fibrosis, chronic bronchitis, and viral- or pollution-triggered asthma. Neutrophils release elastase, a serine protease, that causes increased mucin production and secretion. The molecular mechanisms of elastase-induced mucin production are unknown. We h ypothesized that as part of this mechanism, elastase upregulates expression of a major respiratory mucin gene, MUC5AC. A549, a human lung carcinoma ce ll line that expresses MUC5AC mRNA and protein, and normal human bronchial epithelial cells in an air-liquid interface culture were stimulated with ne utrophil elastase. Neutrophil elastase increased MUC5AC mRNA levels in a ti me-dependent manner in both cell culture systems. Neutrophil elastase treat ment also increased MUC5AC protein levels in A549 cells. The mechanism of M UC5AC gene regulation by elastase was determined in A549 cells. The inducti on of MUC5AC gene expression required serine protease activity; other class es of proteases had no effect on MUC5AC gene expression. Neutrophil elastas e increased MUC5AC mRNA levels by enhancing mRNA stability. This is the fir st report of mucin gene regulation by this mechanism.