Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells

Jeanclare Seagrave,Helmut H Albrecht,Gail Solomon,Duncan F Rogers,David B Hill

doi:10.1186/1465-9921-13-98

Abstract

BackgroundTherapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Several types of drugs are available with different possible modes of action. We examined the effects of guaifenesin (GGE), N-acetylcysteine (NAC) and ambroxol (Amb) on differentiated human airway epithelial cells stimulated with IL-13 to produce additional MUC5AC.MethodsAfter IL-13 pre-treatment (3 days), the cultures were treated with GGE, NAC or Amb (10–300 μM) in the continued presence of IL-13. Cellular and secreted MUC5AC, mucociliary transport rates (MTR), mucus rheology at several time points, and the antioxidant capacity of the drugs were assessed.ResultsIL-13 increased MUC5AC content (~25%) and secretion (~2-fold) and decreased MTR, but only slightly affected the G’ (elastic) or G” (viscous) moduli of the secretions. GGE significantly inhibited MUC5AC secretion and content in the IL-13-treated cells in a concentration-dependent manner (IC50s at 24 hr ~100 and 150 μM, respectively). NAC or Amb were less effective. All drugs increased MTR and decreased G’ and G” relative to IL-13 alone. Cell viability was not affected and only NAC exhibited antioxidant capacity.ConclusionsThus, GGE effectively reduces cellular content and secretion of MUC5AC, increases MTR, and alters mucus rheology, and may therefore be useful in treating airway mucus hypersecretion and mucostasis in airway diseases.

Highlights

Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important
We demonstrated that GGE reduced the cellular content and secretion of MUC5AC, altered the viscoelastic properties of the secretions, and improved mucociliary transport rates (MTR) [8]
Viability It is possible that a decrease in secretion or altered mucociliary transport could result from toxicity of the drugs tested

Summary

Introduction

Therapeutic intervention in the pathophysiology of airway mucus hypersecretion is clinically important. Airway bacterial or viral infections, asthma or chronic bronchitis can cause excessive mucus production and secretion. Combined with possible rheological changes, altered ciliary beating or uncoupling from the ciliary movement due to changes in liquid layer depth, these conditions can cause defective mucociliary clearance and airway mucus accumulation [1,4]. These factors lead, in turn, to coughing and subjective discomfort. In extreme cases, such as uncontrolled asthma, complete blockage of the airways with mucus can occur. There is, a need for improved therapeutic agents to improve mucociliary function under these pathophysiological conditions

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