title: Effects of guaifenesin, N-acetylcysteine, and ambroxol on MUC5AC and mucociliary transport in primary differentiated human tracheal-bronchial cells.
abstract: BACKGROUND
  Therapeutic 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.
  
  
  METHODS
  After 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.
  
  
  RESULTS
  IL-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.
  
  
  CONCLUSIONS
  Thus, 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.
authors.affiliation: Lovelace Respiratory Research Institute, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108, USA. jseagrav@LRRI.org
authors.forename: Jeanclare
authors.initials: J
authors.lastname: Seagrave
authors.forename: Helmut H
authors.initials: HH
authors.lastname: Albrecht
authors.forename: David B
authors.initials: DB
authors.lastname: Hill
authors.forename: Duncan F
authors.initials: DF
authors.lastname: Rogers
authors.forename: Gail
authors.initials: G
authors.lastname: Solomon
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000551:Ambroxol / Q000494:pharmacology*; D002478:Cells, Cultured; D005100:Expectorants / Q000494:pharmacology; D006140:Guaifenesin / Q000494:pharmacology*; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D055271:Mucin 5AC / Q000378:metabolism*; D009079:Mucociliary Clearance / Q000187:drug effects / Q000502:physiology*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism*
chemical_list: D005100:Expectorants; D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D000551:Ambroxol; D006140:Guaifenesin; D000111:Acetylcysteine