Mucus hypersecretion is a major pathophysiologic feature of chronic bronchitis, Although mucus functions as a barrier and facilitator of mucociliary clearance, persistent mucus hypersecretion results in airway obstruction and compromised clearance of inhaled bacteria and particles from airways of COPD patients. Treatment of mucus hypersecretion is a major therapeutic target, yet mechanisms of mucus hypersecretion remain unknown. Here, we present evidence mat human neutrophil elastase (HNE), a pathophysiologically-relevant stimulant of mucus hypersecretion in airways of patients with chronic bronchitis, provokes tnucin (the glycoprotein component of mucus) release by human airway epithelial cells in vitro. Signaling molecules involved in HNE-induced mucin hypersecretion include protein kinase C, specifically the delta isoform , and the myristoylated alanine-rich C kinase substrate (MARCKS) protein. These molecules represent potential therapeutic targets to regulate mucin secretion in patients.
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