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.