title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan. takao971@belle.shiga-med.ac.jp
authors.forename: Takao
authors.initials: T
authors.lastname: Ogawa
authors.forename: Shino
authors.initials: S
authors.lastname: Shimizu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D002460:Cell Line; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009077:Mucins / Q000378:metabolism; D009093:Mucus; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D055571:Secretory Pathway / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009077:Mucins; D006493:Heparin