title: Role of thrombin in chronic rhinosinusitis-associated tissue remodeling.
abstract: BACKGROUND
  Thrombin, the effector enzyme of the coagulation system, has been reported to promote inflammatory responses in nasal diseases through its protease-activated receptors (PARs). Chronic rhinosinusitis (CRS) is characterized by increased deposition of extracellular matrix proteins, tissue remodeling, and formation of nasal polyps. The role of thrombin in chronic nasal inflammation-associated tissue remodeling still has not been appraised. This study was conducted to elucidate the role of thrombin in the pathogenesis of CRS.
  
  
  METHODS
  Nasal secretion was collected from patients with CRS with nasal polyp (CRSwNP) with asthma (n = 9), CRSwNP without asthma (n = 10), allergic rhinitis (n = 7), and control patients (n = 3). The concentrations of thrombin, thrombin-antithrombin (TAT) complex, and vascular endothelial growth factor (VEGF) were evaluated by enzyme immunoassays. The concentration of thrombin and TAT complex was measured in nasal secretion from each group of patients, and VEGF was measured in culture medium from airway epithelial cells treated with thrombin or thrombin receptor agonist peptide.
  
  
  RESULTS
  Thrombin and TAT complex were significantly increased in nasal secretion of patients with CRSwNPs with asthma compared with the control group. Thrombin and PAR-1 agonist peptide significantly stimulated VEGF secretion from cultured human airway epithelial cells.
  
  
  CONCLUSIONS
  The results of this study showed that there is increased activation of the coagulation system in the nasal mucosa of CRS patients and that thrombin may play a role in nasal polyp formation by stimulating VEGF production from airway epithelial cells.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Shiga, Japan. sshino@belle.shiga-med.ac.jp
authors.forename: Shino
authors.initials: S
authors.lastname: Shimizu
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Takao
authors.initials: T
authors.lastname: Ogawa
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.forename: Eriko
authors.initials: E
authors.lastname: Hoshi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000328:Adult; D000368:Aged; D056151:Airway Remodeling; D001249:Asthma; D012634:Bodily Secretions / Q000378:metabolism*; D002460:Cell Line; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*; D009298:Nasal Polyps; D009666:Nose / Q000473:pathology; D018179:Receptors, Thrombin / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis; D012852:Sinusitis; D013917:Thrombin / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000494:pharmacology
chemical_list: D018179:Receptors, Thrombin; D042461:Vascular Endothelial Growth Factor A; D013917:Thrombin