title: Effect of guaifenesin on mucin production, rheology, and mucociliary transport in differentiated human airway epithelial cells.
abstract: Guaifenesin is widely used to alleviate symptoms of excessive mucus accumulation in the respiratory tract. However, its mechanism of action is poorly understood. The authors hypothesized that guaifenesin improves mucociliary clearance in humans by reducing mucin release, by decreasing mucus viscoelasticity, and by increasing mucociliary transport. To test these hypotheses, human differentiated airway epithelial cells, cultured at an air-liquid interface, were treated with clinically relevant concentrations of guaifenesin by addition to the basolateral medium. To evaluate the effect on mucin secretion, the authors used an anzyme-linked immunosorbent assay (ELISA) to measure the amounts of MUC5AC protein in apical surface fluid and cell lysates. To measure mucociliary transportability, additional cultures were treated for 1 or 6 hours with guaifenesin, and the movement of cell debris was measured from video data. Further, the authors measured mucus dynamic viscoelasticity using a micro cone and plate rheometer with nondestructive creep transformation. Guaifenesin suppressed mucin production in a dose-dependent manner at clinically relevant concentrations. The reduced mucin production was associated with increased mucociliary transport and decreased viscoelasticity of the mucus. Viability of the cultures was not significantly affected. These results suggest that guaifenesin could improve mucociliary clearance in humans by reducing the release and/or production of mucins, thereby altering mucus rheology.
authors: Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. jseagrav@LRRI.org
authors: JeanClare
authors: J
authors: Seagrave
authors: Helmut
authors: H
authors: Albrecht
authors: Yong Sung
authors: YS
authors: Park
authors: Bruce
authors: B
authors: Rubin
authors: Gail
authors: G
authors: Solomon
authors: K Chul
authors: KC
authors: Kim
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D006140:Guaifenesin / Q000494:pharmacology*; D006801:Humans; D055271:Mucin 5AC / Q000378:metabolism; D009077:Mucins / Q000096:biosynthesis* / Q000378:metabolism; D009079:Mucociliary Clearance / Q000187:drug effects*; D009093:Mucus / Q000187:drug effects / Q000378:metabolism; D012212:Rheology / Q000379:methods; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014783:Viscosity / Q000187:drug effects
chemical_list: C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D006140:Guaifenesin