Involvement of the glucocorticoid receptor in the pathogenesis of rheumatoid arthritis.
The glucocorticoid receptor (GR) is a ligand-inducible transcription factor which controls the expression of several genes. Its cognate ligand, the glucocorticoids, induces receptor activation by binding to the cytoplasmic located receptor, ultimately leading to translocation of the receptor/hormone complex into the nucleus and the regulation of gene activity. Because glucocorticoids are widely used for suppression of inflammation in rheumatoid arthritis (RA), we investigated whether the expression level of GR is correlated with RA. We designed a study to detect the total amount of GR in lymphocytes of untreated RA patients, glucocorticoid-treated RA patients, and healthy controls. We observed a significant change in the expression levels of GR. Untreated RA patients exhibited a significantly higher amount of GR than the healthy controls, whereas glucocorticoid-treated RA patients showed a strongly decreased receptor density. These results seem to reflect a functional dysregulation of the HPA axis and may lead to a better understanding of the pathogenesis of RA.
Neeck
Gunther
G
Kerckhoff Clinic and Foundation, Bad Nauheim, Germany. gunther.neeck@kerckhoff.med-uni-giessen.de
Kluter
Andreas
A
Dotzlaw
Helmut
H
Eggert
Martin
M
D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D001327:Autoimmune Diseases / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008214:Lymphocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D011965:Receptors, Glucocorticoid / Q000097:blood / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D011239:Prednisolone