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

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.

Continuous mucociliary transport by primary human airway epithelial cells in vitro

“…In general, measurements of CBF and MCT in this study were similar to values obtained in other studies of cultured HBE cells (6,25,29,38). For example, Matsui et al (29) reported mucus transport velocities of 20 -80 m/s, and Liu et al (25) reported a CBF of 9 -10 Hz in cultured HBE cells.…”

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…These cells express basal cell markers including cytokeratin 5 and the transcription factor p63 (Hackett et al, 2011a) and have been used as models of basal cells. al., 2010), mucociliary transport (Seagrave et al, 2012), airway toxicology (Mathis et al, 2013;Watson et al, 2010), electrophysiology (Hirsh et al, 2008), and bacterial and viral infection studies (Deng et al, 2014;Mitchell et al, 2011;Palmer et al, 2012;Ren and Daines, 2011;Ren et al, 2012). The MucilAir cultures have been characterized electrophysiologically and are fully functional: the activity of the main epithelial ionic channels, such as CFTR, EnaC, Na/K ATPase, etc.…”

Differentiation mucolytic therapy for acute and chronic bronchopulmonary diseases in pediatric practice

“…Секре-торные гены (MUC2, MUC5AC, MUC5B, MUC6, MUC7, MUC8) ответственны за выработку секрета и его вяз-коэластические свойства. Гены MUC5AC и MUC5B ответственны за гельформирующие муцины, выра-батываемые соответственно в бокаловидных клетках и железах подслизистого слоя, что имеет значение при воспалительных заболеваниях [7,8]. Мукопроте-ин MUC5AC считается биомаркером бокаловидных клеток респираторного тракта и широко используется для изучения их метаплазии in vivo и in vitro [8].…”

“…Секрет разжижается путем расщепления кислых мукополисахаридов и дезоксирибонуклеи-новых кислот, одновременно улучшается выделение секрета [28]. В эксперименте установлено, что ам-броксол в отличие от ацетилцистеина и гвайфенезина лишь незначительно подавляет секрецию муцинов MUC5AC и снижает уровень их клеточного содержа-ния, причем этот эффект не зависит от концентрации препарата [8].…”