Abstract
Mucus hypersecretion in airways is a common pathological change observed in chronic inflammatory diseases and asthma. We investigated the new role of cell attachment to the extracellular matrix (ECM) on the production of the airway mucus protein, MUC5AC mucin, in human airway epithelial cells, NCI-H292. MUC5AC levels of cells cultured on low adhesion plates were 10-fold higher than those of cells cultured on adhesion plates. Cells cultured on bovine serum albumin (BSA) coated plates, which produce low adhesion conditions, also induced the up-regulation of MUC5AC. Mucin staining by PAS and MUC5AC immunodetection confirmed that mucin proteins were overproduced under low adhesion conditions. The major adhesion molecule between cells and the ECM was integrins. A time-course experiment showed that the expression patterns of integrin β1 and MUC5AC protein were inversely proportional. The inhibition of integrin β1 induced an increase in MUC5AC production in cells cultured under adhesion conditions, but not under low adhesion conditions. These results suggested that cell attachment regulates MUC5AC production, which is up-regulated by low adhesion to the ECM, and MUC5AC production is inversely proportional to the function of integrin β1.
Highlights
Asthma, a chronic inflammatory disease of the bronchial tubes, is characterized by hyperreactivity to various external stimuli, airway inflammations, and airway obstructions [1]
bovine serum albumin (BSA) coating inhibits initial cell attachment to the carrier surface, and is a common method used to reduce cell attachment. This result suggested that cell attachment was a part of the regulation of MUC5AC production and that culturing cells under low adhesion conditions induced an up-regulation in the levels of MUC5AC mucin
When the cells were cultured under low adhesion conditions, cell attachment was markedly reduced compared to the attachment of the cells that were cultured under adhesion conditions (Figure 1)
Summary
A chronic inflammatory disease of the bronchial tubes, is characterized by hyperreactivity to various external stimuli, airway inflammations, and airway obstructions [1]. Airway obstructions are caused by bronchospasms and mucus build ups from airway epithelial cells. The mucus layer, which comprise water, ions, and mucin glycoproteins, coats the airway epithelium and is essential for host defense against foreign pathogens or external irritants. Mucins, which are high-molecularweight and heavily-glycosylated proteins, are needed to maintain the the viscosity of the mucus layer and are secreted by the mucosal goblet cells [2]. Mucin proteins in the mucus layer are overproduced in the respiratory tracts of patients with asthma. Thereafter, the overproduction of the mucus layer by mucins causes airway obstruction [3,4]
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