title: Nuclear translocation of the glucocorticoid receptor in fibroblasts of asthmatic patients with nasal polyposis insensitive to glucocorticoid treatment.
abstract: BACKGROUND
  Nasal polyposis (NP) is treated with topical glucocorticoids (GC). Some patients require endoscopic nasal surgery because GC treatment is ineffective. To exert its function, the GC needs to bind with the GC receptor (GR) and the GC-GR complex moves to the cell nucleus. Our aim was to establish whether the poor response to GC is due to an alteration in the translocation of the GR to the nucleus.
  
  
  METHODS
  We performed nasal fibroblast cell cultures from seven healthy controls and 12 patients with NP and asthma. Fibroblasts were incubated with budesonide or dexamethasone (10(-7) M) for different times (30 min to 4 h) and GR translocation was analyzed by immunocytochemistry.
  
  
  RESULTS
  Both GC induced GR translocation in every group, doubling its concentration in the cell nucleus (30 min) compared to baseline. There were no differences in GR translocation between controls and patients, nor differences related to the severity of asthma or intolerance to non-steroidal anti-inflammatory drugs (NSAIDs). Atopic subjects showed a decrease in GR translocation with budesonide (1 h, 3 h and 4 h, P<0.05) and dexamethasone (30 min and 2 h, P<.05).
  
  
  CONCLUSIONS
  The insensitivity to GC treatment does not appear to be due to an alteration in GR translocation to the nucleus. Neither does the severity of asthma or intolerance to NSAIDs appear to alter GR translocation. The association between atopy and the alteration in GR function deserves further investigation.
authors.affiliation: Servei de Pneumologia i Al.lèrgia Respiratoria, Hospital Clínic, Barcelona, España. cembid@clinic.ub.es
authors.forename: Cristina
authors.initials: C
authors.lastname: Embid
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Bertolín
authors.forename: Laura
authors.initials: L
authors.lastname: Pujols
authors.forename: Isam
authors.initials: I
authors.lastname: Alobid
authors.forename: Joaquim
authors.initials: J
authors.lastname: Mullol
authors.forename: César
authors.initials: C
authors.lastname: Picado
mesh_terms: D021581:Active Transport, Cell Nucleus; D018927:Anti-Asthmatic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D001249:Asthma / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D055963:Asthma, Aspirin-Induced / Q000188:drug therapy / Q000473:pathology; D019819:Budesonide / Q000493:pharmacokinetics / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects; D003907:Dexamethasone / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005938:Glucocorticoids / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009297:Nasal Mucosa / Q000473:pathology; D009298:Nasal Polyps / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000378:metabolism*; D012720:Severity of Illness Index
chemical_list: D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D019819:Budesonide; D003907:Dexamethasone