Expression and distribution of glucocorticoid receptor isoforms in eosinophilic chronic rhinosinusitis

Objective: Patients with eosinophilic chronic rhinosinusitis (ECRS) show a high percentage of eosinophilic infiltration in the paranasal sinus mucosa. It is well documented that topical steroids have a beneficial effect in ECRS with nasal polyposis. We investigated mucosal distribution and cellular localization of glucocorticoid receptor (GR) isoform expression in human paranasal sinuses in relation to the clinical characteristics of eosinophilic chronic rhinosinusitis (ECRS) patients. Methods: Mucosal specimens were obtained from 20 sinusitis patients by endoscopic sinus surgery (ESS). Quantitative fluorescence immunohistochemical analysis was employed to examine the degree of glucocorticoid receptor (GR) isoform expression in sinus mucosa specimens. An RT-PCR procedure was performed to determine the relative quantities of mRNA for the human GR alpha and GR beta genes. Results: Patients in the ECRS group showed significant increases in peripheral blood eosinophils as compared to the non-ECRS group (16.98% vs. 2.31%). Positive immunoreactivity of GR beta expression was predominantly found to be positive in inflammatory cells. The absolute number of GR beta-positive cells in the ECRS group was increased in comparison with that in the non-ECRS group. The difference was statistically significant both in the maxillary (179.7 cells/mm(2) vs. 82.5 cells/mm(2)) and ethmoid sinus (302.0 cells/mm(2) vs. 61.5 cells/mm(2)) mucosa. The GR beta/GR alpha cell ratio in the ECRS group was elevated when compared with that in the non-ECRS group both in the maxillary and the ethmoid sinus mucosa, with the latter difference being significant. Conclusions: The presence of high peripheral eosinophilia indicates a high likelihood of ECRS disease. Our results support the association of GR beta expression with ECRS. The expression of GR beta immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, may be one of major contributing factors in ECRS. (C) 2010 Elsevier Ireland Ltd. All rights reserved.