title: Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway.
abstract: 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.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Hospital, Campus Mitte, Berlin, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Spies
authors.forename: D H S
authors.initials: DH
authors.lastname: Schaumann
authors.forename: T
authors.initials: T
authors.lastname: Berki
authors.forename: K
authors.initials: K
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Jakstadt
authors.forename: D
authors.initials: D
authors.lastname: Huscher
authors.forename: C
authors.initials: C
authors.lastname: Wunder
authors.forename: G-R
authors.initials: GR
authors.lastname: Burmester
authors.forename: A
authors.initials: A
authors.lastname: Radbruch
authors.forename: R
authors.initials: R
authors.lastname: Lauster
authors.forename: A
authors.initials: A
authors.lastname: Scheffold
authors.forename: F
authors.initials: F
authors.lastname: Buttgereit
mesh_terms: 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*
chemical_list: D051242:Caveolin 1; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone