Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway.
BACKGROUND
Membrane-bound glucocorticoid receptors (mGCR) are up regulated on monocytes after in vitro stimulation and in patients with rheumatoid arthritis. Caveolin-1 is critical for the transport of plasma membrane oestrogen receptors to the cell surface.


OBJECTIVE
To investigate the expression of mGCR in patients with systemic lupus erythematosus (SLE)-a disease with different aetiopathogenesis and treatment regimens-and to examine whether caveolin-1 is critical for the transport of mGCR to the cell surface.


METHODS
Frequencies of mGCR+ peripheral blood mononuclear cells were measured using high-sensitivity immunofluorescent staining and tested for correlation with SLE disease activity and glucocorticoid treatment. Semiquantitative polymerase chain reaction, immunofluorescence, recombinant expression and confocal laser-scanning microscopy were used to search for an association of mGCR with caveolin-1.


RESULTS
The frequencies of mGCR+ monocytes (CD14+) were considerably higher in patients with SLE (n = 33) than in healthy controls (n = 58), whereas B cells (CD19+) were not different in this regard. T cells (CD3+) were always mGCR-. The frequency of mGCR+ monocytes in patients with SLE did not correlate with disease activity, but did inversely correlate with glucocorticoid dosages; this inverse correlation was confirmed by corresponding in vitro experiments with stimulated monocytes. The induced up regulation of mGCR was not accompanied by an up regulation of caveolin-1, and mGCR are not colocalised with caveolin-1 in plasma membrane caveolae.


CONCLUSIONS
mGCR are (a) up regulated in patients with SLE and by inflammatory stimuli and (b) down regulated by glucocorticoids, suggesting a negative feedback loop to control glucocorticoid action. Drugs binding selectively to mGCR may in future prove to be of therapeutic value.
Spies
C M
CM
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Campus Mitte, Berlin, Germany.
Schaumann
D H S
DH
Berki
T
T
Mayer
K
K
Jakstadt
M
M
Huscher
D
D
Wunder
C
C
Burmester
G-R
GR
Radbruch
A
A
Lauster
R
R
Scheffold
A
A
Buttgereit
F
F
D000328:Adult; D016022:Case-Control Studies; D051242:Caveolin 1 / Q000097:blood / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011965:Receptors, Glucocorticoid / Q000097:blood*
D051242:Caveolin 1; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone