Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway

C. M. Spies, D. H.S. Schaumann, T. Berki, K. Mayer, M. Jakstadt, D. Huscher, C. Wunder, G. R. Burmester, A. Radbruch, R. Lauster, A. Scheffold, F. Buttgereit

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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.

Original languageEnglish
Pages (from-to)1139-1146
Number of pages8
JournalAnnals of the rheumatic diseases
Volume65
Issue number9
DOIs
Publication statusPublished - Sep 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

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    Spies, C. M., Schaumann, D. H. S., Berki, T., Mayer, K., Jakstadt, M., Huscher, D., Wunder, C., Burmester, G. R., Radbruch, A., Lauster, R., Scheffold, A., & Buttgereit, F. (2006). Membrane glucocorticoid receptors are down regulated by glucocorticoids in patients with systemic lupus erythematosus and use a caveolin-1-independent expression pathway. Annals of the rheumatic diseases, 65(9), 1139-1146. https://doi.org/10.1136/ard.2005.048272