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Repression of inflammatory responses in the absence of DNA binding by the glucocorticoid receptor
Author(s) -
Reichardt Holger M.,
Tuckermann Jan P.,
Göttlicher Martin,
Vujic Maja,
Weih Falk,
Angel Peter,
Herrlich Peter,
Schütz Günther
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.24.7168
Subject(s) - biology , glucocorticoid receptor , transcription factor , glucocorticoid , transcription (linguistics) , psychological repression , immune system , microbiology and biotechnology , promoter , nfkb1 , gene expression , gene , immunology , genetics , linguistics , philosophy
The glucocorticoid receptor (GR) acts both as a transcription factor itself on genes carrying GR response elements (GREs) and as a modulator of other transcription factors. Using mice with a mutation in the GR, which cannot activate GRE promoters, we examine whether the important anti‐inflammatory and immune suppressive functions of glucocorticoids (GCs) can be established in this in vivo animal model. We find that most actions are indeed exerted in the absence of the DNA‐binding ability of the GR: inhibition of the inflammatory response of locally irritated skin and of the systemic response to lipopolysaccharides. GCs repress the expression and release of numerous cytokines both in vivo and in isolated primary macrophages, thymocytes and CD4 + splenocytes. A transgenic reporter gene controlled by NF‐κB exclusively is also repressed, suggesting that protein– protein interaction with other transcription factors such as NF‐κB forms the basis of the anti‐inflammatory activity of GR. The only defect of immune suppression detected so far concerns the induced apoptosis of thymocytes and T lymphocytes.