title: Inflammation and remodelling patterns in early stage chronic rhinosinusitis.
abstract: BACKGROUND
  A distinct set of inflammatory and remodelling factors have been found elevated in chronic rhinosinusitis.
  
  
  OBJECTIVE
  The investigation of their expression in early stage disease may reveal early events in this common disease.
  
  
  METHODS
  Sinonasal mucosal samples from nine patients with early stage CRSsNP were taken from the inferior and middle turbinates, the uncinate process, maxillary sinus, anterior ethmoid, bulla ethmoidalis and the posterior ethmoid and measured for TGF-beta 1 and it's receptors, MPO protein as well as pro-inflammatory cytokines (TNF-alpha and IL-1beta) and the Th1 cell signature (IFN-gamma and T-bet). As outcome parameter for TGF-beta signalling collagen deposition was analysed. Inferior turbinates from patients undergoing (rhino-) septoplasty were collected as controls.
  
  
  RESULTS
  TGF-beta 1 protein concentrations were significantly increased in the maxillary sinuses (P = 0.006), the uncinate process (P = 0.01), the anterior ethmoid including the bulla ethmoidalis (P = 0.005) and the posterior ethmoid (P = 0.037) when compared to the inferior and middle turbinates. Collagen deposition was significantly increased in the maxillary sinus when compared to the inferior turbinates (P = 0.008). In contrast, mRNA for TGF-beta receptors, Th1 related markers (IFN-gamma and T-bet), pro-inflammatory cytokines (IL-1 beta and TNF-alpha), and MPO protein as neutrophil marker were expressed at all locations but showed no significant differences between the various locations. TGF-beta 1 mRNA expression in inferior turbinates of CRSsNP was significantly higher when compared to inferior turbinates of controls (P = 0.017). The pro-inflammatory cytokines and Th1-related cytokines did not show an upregulation in inferior turbinates of CRSsNP when compared to controls.
  
  
  CONCLUSIONS
  In early stage chronic sinus disease, TGF-beta protein is expressed in significantly higher concentrations within the paranasal sinuses when compared to turbinates, whereas pro-inflammatory, neutrophilic and Th1 markers did not show any difference. These findings suggest that TGF-beta plays a central role in the initiation of CRSsNP, and represents a major target for further research and future intervention.
authors.affiliation: Upper Airway Research Laboratory, Department of Oto-Rhino-Laryngology, Ghent University Hospital, Ghent, Belgium. Nicholas.Vanbruaene@Ugent.be
authors.forename: N
authors.initials: N
authors.lastname: Van Bruaene
authors.forename: Perez-Novo
authors.initials: PN
authors.lastname: C
authors.forename: K
authors.initials: K
authors.lastname: Van Crombruggen
authors.forename: N
authors.initials: N
authors.lastname: De Ruyck
authors.forename: G
authors.initials: G
authors.lastname: Holtappels
authors.forename: P
authors.initials: P
authors.lastname: Van Cauwenberge
authors.forename: P
authors.initials: P
authors.lastname: Gevaert
authors.forename: C
authors.initials: C
authors.lastname: Bachert
mesh_terms: D000328:Adult; D056151:Airway Remodeling; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D008297:Male; D008443:Maxillary Sinus / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D012852:Sinusitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D018417:Th1 Cells / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D007377:Interleukin-3; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D053773:Transforming Growth Factor beta1; C404145:myelopoietin; D016179:Granulocyte Colony-Stimulating Factor