title: RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP.
abstract: BACKGROUND
  The receptor for advanced glycation end products (RAGE) is a multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble (sRAGE) form. RAGE is reported to play a role in diverse pathologies including lower airway conditions, but the exact mechanism of action remains poorly understood. In the upper airways, the involvement of RAGE remains completely unexplored.
  
  
  OBJECTIVE
  To investigate the involvement of RAGE in the human upper airway conditions chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP).
  
  
  METHODS
  Protein levels of sRAGE, mRAGE, IL-5, and eosinophil cationic protein (ECP) were quantitatively assessed in inflamed tissue of CRSsNP and CRSwNP patients. Nasal tissue of subjects without disease served as control. Ex vivo human sinonasal tissue stimulation assays were used to assess the effect of Staphylococcus aureus and ECP on sRAGE processing.
  
  
  RESULTS
  sRAGE protein levels were higher in CRSsNP tissue, whereas mRAGE protein levels were lower than in controls. In CRSwNP patients, both tissue sRAGE and mRAGE protein levels were reduced. Low tissue sRAGE protein concentrations were associated with high IL-5 and ECP protein levels. In vitro, S aureus induced the release of sRAGE from the tissue, while ECP was shown to be implicated in the breakdown of free sRAGE.
  
  
  CONCLUSIONS
  We demonstrate for the first time that RAGE protein is highly expressed in human upper airways under normal physiology and that it is subject to differential processing in CRSsNP and CRSwNP, identifying S aureus and ECP as novel and crucial players in this process.
authors.affiliation: Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium. koen.vancrombruggen@ugent.be
authors.forename: Koen
authors.initials: K
authors.lastname: Van Crombruggen
authors.forename: Gabriele
authors.initials: G
authors.lastname: Holtappels
authors.forename: Natalie
authors.initials: N
authors.lastname: De Ruyck
authors.forename: Lara
authors.initials: L
authors.lastname: Derycke
authors.forename: Peter
authors.initials: P
authors.lastname: Tomassen
authors.forename: Claus
authors.initials: C
authors.lastname: Bachert
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000293:Adolescent; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D047150:Eosinophil Cationic Protein / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009298:Nasal Polyps / Q000150:complications / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D012220:Rhinitis / Q000209:etiology* / Q000473:pathology; D012852:Sinusitis / Q000209:etiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators; D015848:Interleukin-5; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D047150:Eosinophil Cationic Protein; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human