Expression Analysis of the Glucocorticoid Receptor and the Nuclear Factor-kB Subunit p50 in Lymphocytes from Patients with Rheumatoid Arthritis

MARTIN EGGERT, ANDREAS KLÜTER, DIETRICH RUSCH, KLAUS L. SCHMIDT, HELMUT DOTZLAW, MARTIN SCHULZ, WOLFGANG PABST, JÖRN BÖKE, RAINER RENKAWITZ, and GUNTHER NEECK

ABSTRACT.

Objective. To study a possible relationship between expression of the transcription factor glucocorticoid receptor (GR), which mediates antiinflammatory effects, and the transcription factor p50, which mediates proinflammatory effects, in peripheral blood mononuclear cells (PBMC) of patients with rheumatoid arthritis (RA).

Methods. Expression analysis of GR and nuclear factor-kB subunit p50 in PBMC was performed by semiquantitative immunoblotting.

Results. GR and p50 expression in PBMC were significantly increased in patients with RA who had never received corticosteroids. In contrast, GR density is decreased in glucocorticoid treated RA patients. In addition, a dependency between increased GR expression and increased p50 expression was found.

Conclusion. The pathogenesis of RA is not reflected in diminished GR expression but rather in an increased expression level of GR, as well as increased p50 expression in PBMC. Corticosteroids as the major therapeutic drugs result in a reduction of these increased GR and p50 expression levels. (J Rheumatol 2002;29:2500-6)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
NUCLEAR FACTOR-kB
GLUCOCORTICOID RECEPTOR
LYMPHOCYTES

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From the Klinikum Südstadt, Klinik für Innere Medizin, Rostock; Kerckhoff Klinik, Abteilung Rheumatologie, Bad Nauheim; Zentrum für Innere Medizin der Universität, Lehrstuhl für Rheumatologie, Giessen; and Institut für medizinische Statistik der Universität, Giessen; Institut für Genetik der Universität, Giessen, Germany.

Supported by Max Planck Gesellschaft/Kerckhoff-Institut; Forschungsrat, the Stiftung W.G. Kerckhoff, Bad Nauheim; and the Zentrum für Innere Medizin, Lehrstuhl für Rheumatologie, Universität Giessen.

M. Eggert, PhD; A. Klüter, MD; G. Neeck, MD, Professor, Klinik für Innere Medizin, Klinikum Südstadt; D. Rusch, PhD; M. Schulz, PhD; H. Dotzlaw, Research Associate, Kerckhoff Klinik, Abteilung Rheumatologie; K.L. Schmidt, MD, Professor, Zentrum für Innere Medizin der Universität, Lehrstuhl für Rheumatologie; W. Pabst, Research Associate, Institut für medizinische Informatik der Universität; J. Böke, PhD Student; R. Renkawitz, PhD, Professor, Institut für Genetik der Universität.

Address reprint requests to Prof. Dr. G. Neeck, Klinik für Innere Medizin, Klinikum Südstadt Rostock, Südring 81, 18059 Rostock, Germany. E-mail: gunther.neeck@kliniksued-rostock.de

Submitted March 1, 2002; revision accepted June 5, 2002.

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