title: Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) digest extracellular matrix components and might be important mediators of tissue remodeling. Proteinase activated receptor-2 (PAR-2) is expressed in a variety of cell types including epithelial cells. PAR-2 receptors are activated by serine proteases such as trypsin and mast cell tryptase and have been implicated in inflammation.
  
  
  OBJECTIVE
  To study the effects of PAR-2-mediated airway epithelial cell activation on the production of MMP-9.
  
  
  METHODS
  A specific PAR-2-activating peptide and trypsin were used to activate the human airway epithelial cell line A549 as well as primary cultures of small airway epithelial cells (SAEC). MMP-2 and MMP-9 messenger RNA and enzymatic activity were evaluated by RT-PCR and gelatin zymography, respectively.
  
  
  RESULTS
  PAR-2-activating peptides upregulated MMP-9 mRNA expression and release of MMP-9 enzymatic activity from airway epithelial cells but had no effect on MMP-2 production. Dexamethasone and budesonide (10(-6) to 10(-10) mmol) inhibited PAR-2-mediated MMP-9 release. Pretreatment with indomethacin indicated that MMP-9 release was not prostaglandin dependent. Inhibitors of the MAP kinase MEK- 1, and NFkappaB showed that both pathways are important for PAR-2-mediated MMP-9 release. Trypsin, a physiologic PAR-2 activator, upregulated MMP-9 but also MMP-2 release from airway epithelial cells.
  
  
  CONCLUSIONS
  PAR-2 receptors appear to play an important role in the regulation of MMP-9 release from airway epithelial cells. As such, these receptors may be critical elements in tissue remodeling in asthma and other inflammatory conditions in the airways.
authors.affiliation: Pulmonary Research Group, the Departments Medicine University of Calgary, Calgary, Alberta, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Vliagoftis
authors.forename: A
authors.initials: A
authors.lastname: Schwingshackl
authors.forename: C D
authors.initials: CD
authors.lastname: Milne
authors.forename: M
authors.initials: M
authors.lastname: Duszyk
authors.forename: M D
authors.initials: MD
authors.lastname: Hollenberg
authors.forename: J L
authors.initials: JL
authors.lastname: Wallace
authors.forename: A D
authors.initials: AD
authors.lastname: Befus
authors.forename: R
authors.initials: R
authors.lastname: Moqbel
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000502:physiology*; D012137:Respiratory System / Q000166:cytology*; D015398:Signal Transduction / Q000502:physiology; D014357:Trypsin / Q000494:pharmacology
chemical_list: D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014357:Trypsin; D020780:Matrix Metalloproteinase 9