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.

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

“…The ELISA followed previously described procedures [8], using anti-MUC5AC antibody (45M1; Thermo Fisher), peroxidase-conjugated secondary antibody, and high-sensitivity tetramethylbenzidine development (Thermo Fisher). The washes were diluted 1:4 and the lysates were diluted 1:10 in DPBS for analysis.…”

“…We previously investigated the effects of guaifenesin ([3-(2-methoxyphenoxy)-1,2-propanediol], also called glyceryl guaiacolate ether, GGE) in vitro , using primary human airway epithelial cells differentiated by air-liquid interface culture [8]. These cultures are a complex, organotypic human airway model, containing the major cell types: basal, ciliated, non-ciliated and goblet cells [9].…”

“…These cultures are a complex, organotypic human airway model, containing the major cell types: basal, ciliated, non-ciliated and goblet cells [9]. Using this system, 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]. Here, we extend these observations to conditions in which MUC5AC secretion was increased by culturing with IL-13 for 3 days prior to analysis [10].…”

Guaifenesin Has No Effect on Sputum Volume or Sputum Properties in Adolescents and Adults With Acute Respiratory Tract Infections

“…In contrast to an earlier in vitro study showing that GGE decreased mucociliary transport when applied directly to a ciliated epithelium, 14 a more recent study showed a dose-dependent increase in mucus transport when GGE was introduced into airway cell culture. 15 These data from a clinical study in subjects with an acute upper RTI clearly show no evidence of mucolytic properties and no temporal or drug-associated changes in viscoelasticity or sputum volume.…”

“…This was not supported by the results of sputum volume or percent solid measurements in our study. If GGE were a mucolytic, 14,15 we would expect to see decreased viscoelasticity. In our study, we saw no evidence of either expectorant or mucolytic properties either for GGE or for the placebo.…”