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 GRalpha and GRbeta 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 GRbeta expression was predominantly found to be positive in inflammatory cells. The absolute number of GRbeta-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 GRbeta/GRalpha 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 GRbeta expression with ECRS. The expression of GRbeta immunoreactivity, an endogenous inhibitor of steroid action previously associated with steroid insensitivity, may be one of major contributing factors in ECRS.
Takeda
Kazumasa
K
Department of Otolaryngology, Head and Neck Surgery, Division of Clinical Medical Science, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. kazu-t@umin.net
Takeno
Sachio
S
Hirakawa
Katsuhiro
K
Ishino
Takashi
T
D000328:Adult; D002908:Chronic Disease; D004802:Eosinophilia / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism*; D010256:Paranasal Sinuses / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000150:complications / Q000378:metabolism*; D012852:Sinusitis / Q000150:complications / Q000378:metabolism*; D014018:Tissue Distribution; D055815:Young Adult
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta