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Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway
  1. C M Spies1,
  2. D H S Schaumann2,
  3. T Berki3,
  4. K Mayer1,
  5. M Jakstadt4,
  6. D Huscher2,
  7. C Wunder5,
  8. G-R Burmester1,
  9. A Radbruch2,
  10. R Lauster2,
  11. A Scheffold2,
  12. F Buttgereit1
  1. 1Department of Rheumatology and Clinical Immunology, Charité University Hospital, Campus Mitte, Berlin, Germany
  2. 2German Arthritis Research Centre (DRFZ), Berlin
  3. 3Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Pécs, Hungary
  4. 4Department of Physical Medicine and Rehabilitation, Charité University Hospital
  5. 5Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin
  1. Correspondence to:
    F Buttgereit
    Department of Rheumatology and Clinical Immunology, Charité University Hospital, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany;frank.buttgereit{at}charite.de

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.

Objectives: 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.

Conclusion: 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.

  • cGCR, cytosolic glucocorticoid receptor
  • Dig, digoxigenin
  • ECLAM, European Consensus Lupus Activity Measurement
  • GCR, glucocorticoid receptor
  • LPS, lipopolysaccharide
  • mGCR, membrane-bound glucocorticoid receptors
  • PBMC, peripheral blood mononuclear cells
  • PCR, polymerase chain reaction
  • SLE, systemic lupus erythematosus
  • SLEDAI, SLE Disease Activity Index

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Footnotes

  • Published Online First 31 January 2006

  • Competing interests: None.

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