title: IKK-2 inhibitor TPCA-1 represses nasal epithelial inflammation in vitro.
abstract: BACKGROUND
  Nasal polyposis (NP) is considered a subgroup within chronic rhinosinusitis. NP can be further subdivided into aspirin sensitive- and aspirin tolerant types (ASNP/ ATNP). Although the true etiology of NP has not been identified so far, it is agreed that NP represents an inflammatory disease of the nasal mucosa. Alterations of cellular kinase activities including that of IKK-2 might play a role in this inflammatory process.
  
  
  METHODS
  Paraffin sections of ASNP, ATNP and controls were immunostained with Phospho-IkB-α antibody that detects the direct IKK-2 product (IkB-α. Intensity of epithelial staining was analysed semi-quantitatively by two independent observers. In cultured nasal polyp epithelial cells (NPECs) epithelial derived cytokines IL-8 and GRO α were induced by TNF-α or Staphylococcal supernatants and subsequently repressed by IKK-2 inhibitor TPCA-1.
  
  
  RESULTS
  Significant Phospho-IkB-α staining was observed in the nasal epithelium of ASNP compared to ATNP and controls suggesting strong IKK-2 activation in patients with ASNP in vivo. In vitro, pro-inflammatory cytokines IL-8 and GRO-α in NPECs were significantly repressed by TPCA-1.
  
  
  CONCLUSIONS
  IKK-2 activity is increased in the subgroup of ASNP. IL-8 and GRO-α responses were repressed by IKK-2 inhibitor TPCA-1 in vitro. IKK-2 inhibitors might represent a potential target for anti-inflammatory intervention in ASNP.
authors: Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Munster, Germany. sachsef@ukmuenster.de
authors: F
authors: F
authors: Sachse
authors: K
authors: K
authors: Becker
authors: T J
authors: TJ
authors: Basel
authors: D
authors: D
authors: Weiss
authors: C
authors: C
authors: Rudack
mesh_terms: D000328:Adult; D000368:Aged; D000577:Amides / Q000494:pharmacology*; D054360:Chemokine CXCL1 / Q000187:drug effects; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009297:Nasal Mucosa / Q000473:pathology*; D009298:Nasal Polyps / Q000378:metabolism*; D013876:Thiophenes / Q000494:pharmacology*
chemical_list: D000577:Amides; D054360:Chemokine CXCL1; D016209:Interleukin-8; D016328:NF-kappa B; D013876:Thiophenes; C499326:2-((aminocarbonyl)amino)-5-(4-fluorophenyl)-3-thiophenecarboxamide