Abstract
Mucin 5AC (MUC5AC) hypersecretion induces airway narrowing in patients with asthma, which leads to breathing problems. We investigated the regulation of MUC5AC secretion by extracellular matrix (ECM) proteins in human primary airway epithelial cells from patients with asthma. The addition of type IV collagen to three-dimensional cultured human primary airway epithelial cells, which mimics the airway surface, reduced MUC5AC secretion in the medium, while the addition of laminin increased MUC5AC secretion. Furthermore, the addition of fibronectin did not affect MUC5AC secretion. In particular, the repeated addition of a low concentration of type IV collagen demonstrated a cumulative effect on the reduction in MUC5AC secretion. Human primary cells incubated with type IV collagen showed downregulated extracellular signal-regulated kinase (ERK) activity, which induced MUC5AC hypersecretion but did not affect Akt activity. These results suggest that the addition of type IV collagen to the apical surface of primary cells downregulates MUC5AC secretion and has a cumulative effect on MUC5AC secretion which might be effected via the ERK signaling pathway.
Highlights
The mucus layer in human airways acts as a protective barrier against foreign irritants and is an indispensable primary host defense
The mucin 5AC (MUC5AC) secretion from cells incubated with type IV collagen, laminin, and fibronectin showed the same tendency in the NCI–H292 cells (Figs. 2B, 3B and 4B)
extracellular matrix (ECM) proteins regulated MUC5AC secretion in human primary airway epithelial cells which were derived from patients with asthma and in human lung epithelial cell line NCI–H292 (Figs. 1–5)
Summary
The mucus layer in human airways acts as a protective barrier against foreign irritants and is an indispensable primary host defense. Several in vitro and in vivo studies have described the regulation of MUC5AC expression in human primary airway epithelial cells as a potential therapeutic target in asthma [5]. Known as protein kinase B, is a serine/threonine kinase that is phosphorylated and activated by the integrin pathway It plays important roles in numerous cellular functions, such as cell proliferation, cell migration, and gene transcription [18,19]. The regulation of MUC5AC secretion by ECM proteins in human primary airway epithelial cells was investigated. Our results suggest that type IV collagen downregulates MUC5AC secretion in three-dimensional cultured human primary airway epithelial cells derived from patients with asthma
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