Potential therapy for mucus hypersecretion in chronic obstructive pulmonary disease

Abstract

Mucus hypersecretion is a major pathophysiologic feature of chronic bronchitis. Although mucus functions as a barrier and a facilitator of mucociliary clearance, persistent mucus hypersecretion results in airway obstruction and compromised clearance of inhaled bacteria and particles from the airways of patients with chronic obstructive pulmonary disease. Treatment of mucus hypersecretion is a major therapeutic target; however, mechanisms of mucus hypersecretion remain unknown. Herein, we present evidence that human neutrophil elastase (HNE), a pathophysiologically relevant stimulant of mucus hypersecretion in the airways of patients with chronic bronchitis, provokes release of mucin (the glycoprotein component of mucus) 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 protein. These molecules represent potential therapeutic targets for r...