title: Variations in expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in nasal mucosa of aspirin-sensitive versus aspirin-tolerant patients with nasal polyposis.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) are key enzymes responsible for extracellular matrix degradation contributing to the progressive histological changes seen in lower airway disease, including asthma. MMP-9 and TIMP-1 have also shown some role in the pathogenesis of chronic rhinosinusitis (CRS) and nasal polyposis (NP).
  
  
  OBJECTIVE
  We aim to determine variability in expression of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in sinus tissue from distinct patient populations presenting with nasal polyposis.
  
  
  METHODS
  The expression of MMP-9 and TIMP-1 was investigated in nasal polyp tissue from 6 aspirin-sensitive (AS) and 6 aspirin-tolerant (AT) patients undergoing endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis (CRSwNP). Sinus mucosa from 6 patients with chronic rhinosinusitis without nasal polyposis (CRSsNP) was used as control. The MMP-9 and TIMP-1 expression was measured using immunofluorescence technique and graded using manual and computerized methods.
  
  
  RESULTS
  Expression of TIMP-1 was significantly reduced in the AS group when compared with both the AT and CRSsNP (control) groups (P < .001). The MMP-9/TIMP-1 ratio was significantly increased in the AS group when compared with other patient groups (P < .001). The MMP- 9 expression was similar between study and control groups.
  
  
  CONCLUSIONS
  These results support the importance of MMP-9 and TIMP-1 expression in nasal polyp formation. The decreased expression of TIMP-1 in AS patients may promote the effects of MMP-9 expression and thus contribute to tissue remodeling and inflammatory changes. This finding may lead to further understanding of disease severity and resistance to treatment in this group of patients, as well as the pathogenesis of nasal polyps.
authors.affiliation: University of Colorado, Department of Otolaryngology, Aurora, 80045, USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Mudd
authors.forename: Rohit K
authors.initials: RK
authors.lastname: Katial
authors.forename: Raeful
authors.initials: R
authors.lastname: Alam
authors.forename: Samantha
authors.initials: S
authors.lastname: Hohensee
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramakrishnan
authors.forename: Todd T
authors.initials: TT
authors.lastname: Kingdom
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D001706:Biopsy; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology / Q000601:surgery; D009298:Nasal Polyps / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; D001241:Aspirin