title: Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-beta1.
abstract: Glucocorticoids (GCs) are considered drugs of choice for treating nasal polyps (NPs). However, a subset of patients shows a limited clinical response even to high doses of GCs. Altered expression of glucocorticoid receptors (GRs), namely GR-alpha; and GR-beta;, is a potential mechanism underlying GC insensitivity. GCs modulate the expression of several cytokines, including transforming growth factor-beta (TGF-beta), which may contribute to cellular proliferation in NPs. The study investigates some biomolecular features of GC-resistant NPs, and examines possible differences from normal mucosa (NM).
  
  
  
  Radioligand binding assay (binding) was used to determine GR-alpha; binding capacity; Western blotting was used to evaluate GR-alpha;, GR-beta;, and TGF-beta; expression and GR-alpha; subcellular distribution. NPs were sampled in 32 patients during ethmoidectomy; NM was taken from 15 healthy patients during rhinoplasty.
  
  
  
  GR-alpha; was present in NPs and NM, with lower affinity for the ligand in NPs. GR-alpha; was prevalent in the cytosol of NPs that were GR-alpha-negative to the binding assay. GR-beta was expressed in NPs and absent in the majority of NM. TGF-beta1 expression was higher in NPs than in NM.
  
  
  
  GR-beta and TGF-beta1 might be involved in NP pathogenesis, but their role in modulating GC sensitivity is still unclear.
authors.affiliation: Otorhinolaryngology, Department of Clinical and Biological Sciences, University of Torino, San Luigi Hospital, Orbassano, Torino, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Aversa
authors.forename: C
authors.initials: C
authors.lastname: Ondolo
authors.forename: G
authors.initials: G
authors.lastname: Abbadessa
authors.forename: F
authors.initials: F
authors.lastname: Piccione
authors.forename: V
authors.initials: V
authors.lastname: Carriero
authors.forename: A
authors.initials: A
authors.lastname: Fulcheri
authors.forename: A
authors.initials: A
authors.lastname: Lauria
authors.forename: S
authors.initials: S
authors.lastname: De Francia
authors.forename: S
authors.initials: S
authors.lastname: Racca
mesh_terms: D004351:Drug Resistance; D004591:Electrophoresis, Polyacrylamide Gel; D004724:Endoscopy; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery; D011241:Prednisone / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D053773:Transforming Growth Factor beta1; D011241:Prednisone