Heparin Inhibits Mucus Hypersecretion in Airway Epithelial Cells

Abstract

Background Heparin is one of the most important anticoagulant drugs. It has been known that heparin also possesses anti-inflammatory activities. Mucus hypersecretion is an important characteristic of airway inflammation. However, little is known about the regulatory effects of heparin on mucus hypersecretion in airway epithelial cells. To elucidate the anti-inflammatory function of heparin in airway epithelial cells, we examined the in vivo effects of heparin on mucus hypersecretion and neutrophil infiltration in rat nasal epithelium. We also examined the in vitro effects of heparin on mucin production and IL-8 secretion from cultured human airway epithelial cells. Methods We induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal lipopolysaccharide (LPS) instillation. The effects of intranasal instillation with heparin on mucus production and neutrophil infiltration were examined. In vitro effects of heparin on airway epithelial cells were examined using cultured NCI-H292 cells. Mucus secretion was evaluated by enzyme-linked immunosorbent assay using an anti-MUC5AC monoclonal antibody. Results Intranasal instillation with unfractionated heparin (UFH; 100 IU/0.1 mL) or low molecular weight heparin (LMWH; 100 IU/0.1 mL) at 30 minutes before LPS instillation significantly inhibited LPS-induced mucus production and neutrophil infiltration in rat nasal epithelium. UFH or LMWH inhibited tumor necrosis factor alpha (10 ng/mL)–induced secretion of MUC5AC and IL-8 from NCI-H292 cells in a dose-dependent manner (0.01–10 IU/mL). MUC5AC mRNA expression was also significantly inhibited. Conclusion These results indicate that heparin inhibits airway mucus hypersecretion in airway epithelial cells directly and indirectly through the suppression of IL-8 secretion and neutrophil infiltration.