Buchumschlag

Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages

Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-de...

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Bibliographische Detailangaben
Hauptverfasser: Kleiman, Anna (VerfasserIn) , Hübner, Sabine (VerfasserIn) , Hofer, Stefan (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 31 Oct 2011
In: The FASEB journal
Year: 2011, Jahrgang: 26, Heft: 2, Pages: 722-729
ISSN:1530-6860
DOI:10.1096/fj.11-192112
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1096/fj.11-192112
Verlag, Volltext: https://www.fasebj.org/doi/10.1096/fj.11-192112
Volltext
Verfasserangaben:Anna Kleiman, Sabine Hübner, Jan M. Rodriguez Parkitna, Anita Neumann, Stefan Hofer, Markus A. Weigand, Michael Bauer, Wolfgang Schmid, Günter Schütz, Claude Libert, Holger M. Reichardt, Jan P. Tuckermann
Beschreibung
Zusammenfassung:Sepsis is controlled by endogenous glucocorticoids (GCs). Previous studies provided evidence that crosstalk of the monomeric GC receptor (GR) with proinflammatory transcription factors is the crucial mechanism underlying the suppressive GC effect. Here we demonstrate that mice with a dimerization-deficient GR (GRdim) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-α is normally regulated in these mice, but down-regulation of IL-6 and IL-1β is diminished. LPS-treated macrophages derived from GRdim mice are largely resistant to GC actions in vitro in terms of morphology, surface marker expression, and gene expression. Treatment with recombinant IL-1 receptor antagonist improved survival of GRdim mice and mice lacking the GR in macrophages (GRLysMCre) mice. This suggests that regulation of IL-1β in macrophages by GCs is pivotal to control sepsis.—Kleiman, A., Hübner, S., Rodriguez Parkitna, J. M., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., Schmid, W., Schütz, G., Libert, C., Reichardt, H. M., Tuckermann, J. P. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages.
Beschreibung:Gesehen am 06.02.2019
Beschreibung:Online Resource
ISSN:1530-6860
DOI:10.1096/fj.11-192112

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