Increased expression of glucocorticoid receptor beta messenger RNA in patients with ankylosing spondylitis.
BACKGROUND
Glucocorticoids have been known to be less effective for treating ankylosing spondylitis (AS) patients than for treating rheumatoid arthritis (RA) patients. To elucidate the mechanisms underlying this phenomenon, we evaluated whether the glucocorticoid receptor (GR) beta expression of the peripheral blood mononuclear cells (PBMCs) in patients with AS is increased compared with patients with RA.


METHODS
PBMCs were isolated from the subjects of 3 study groups: the healthy controls (n=25), the RA patients (n=25), and the AS patients (n=25). All the subjects had never taken corticosteroids and the patients with RA or AS were newly diagnosed. The expression of GR beta messenger RNA (mRNA) was determined by reverse transcription of the total RNA, and this was followed by semi-quantitative polymerase chain reaction analysis (RT-PCR).


RESULTS
The level of GR alpha mRNA expression was not different among three groups. GR beta mRNA expression of the AS patients (2.02 [range: 0.99-7.21], median [25th-75th percentiles]) was enhanced compared with that of the controls (0.78 [range: 0.43-1.62]) and the RA patients (0.98 [range: 0.79-1.18]). The level of GR beta mRNA expression was not related to the inflammatory markers or the disease activity score 28 for the RA patients, and it was not related to the Bath ankylosing spondylitis disease activity index for the AS patients.


CONCLUSIONS
The expression of GR beta mRNA, which is a dominant negative regulator for the glucocorticoid response, was increased in AS patients. The results suggest that the increased expression of GR beta mRNA may be related to the ineffectiveness of glucocorticoids for the treatment of AS.
Lee
Chang-Keun
CK
Division of Allergy and Rheumatology, Department of Internal Medicine, Asan Institute for Life Science, Seoul, Korea.
Lee
Eun Young
EY
Cho
You-Sook
YS
Moon
Keun Ae
KA
Yoo
Bin
B
Moon
Hee-Bom
HB
D000328:Adult; D005260:Female; D015870:Gene Expression; D005819:Genetic Markers; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000235:genetics
D005819:Genetic Markers; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta