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

Anna Kleiman, Sabine Hübner, Jan M Rodriguez Parkitna, Anita Neumann, Stefan Hofer, Markus A Weigand, Michael Bauer, Wolfgang Schmid, Günter Schütz and Claude Libert UGent, et al. (2012) FASEB JOURNAL. 26(2). p.722-729
abstract
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 (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-alpha is normally regulated in these mice, but down-regulation of IL-6 and IL-1 beta is diminished. LPS-treated macrophages derived from GR(dim) 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 GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1 beta in macrophages by GCs is pivotal to control sepsis.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
ACTIVATION, KAPPA-B, REPRESSION, MICE, PHOSPHATASE-1, DEXAMETHASONE, MAP KINASE, INFLAMMATORY RESPONSES, DNA-BINDING, CLP, GR, GENE-EXPRESSION, IL-1 beta
journal title
FASEB JOURNAL
Faseb J.
volume
26
issue
2
pages
722 - 729
Web of Science type
Article
Web of Science id
000300485700023
JCR category
BIOLOGY
JCR impact factor
5.704 (2012)
JCR rank
7/83 (2012)
JCR quartile
1 (2012)
ISSN
0892-6638
DOI
10.1096/fj.11-192112
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2067224
handle
http://hdl.handle.net/1854/LU-2067224
date created
2012-03-15 13:19:07
date last changed
2012-06-26 14:32:37
@article{2067224,
  abstract     = {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 (GR(dim)) are highly susceptible to sepsis in 2 different models, namely cecal ligation and puncture and lipopolysaccharide (LPS)-induced septic shock. TNF-alpha is normally regulated in these mice, but down-regulation of IL-6 and IL-1 beta is diminished. LPS-treated macrophages derived from GR(dim) 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 GR(dim) mice and mice lacking the GR in macrophages (GR(LysMCre)) mice. This suggests that regulation of IL-1 beta in macrophages by GCs is pivotal to control sepsis.},
  author       = {Kleiman, Anna and H{\"u}bner, Sabine and Rodriguez Parkitna, Jan M and Neumann, Anita and Hofer, Stefan and Weigand, Markus A and Bauer, Michael and Schmid, Wolfgang and Sch{\"u}tz, G{\"u}nter and Libert, Claude and Reichardt, Holger M and Tuckermann, Jan P},
  issn         = {0892-6638},
  journal      = {FASEB JOURNAL},
  keyword      = {ACTIVATION,KAPPA-B,REPRESSION,MICE,PHOSPHATASE-1,DEXAMETHASONE,MAP KINASE,INFLAMMATORY RESPONSES,DNA-BINDING,CLP,GR,GENE-EXPRESSION,IL-1 beta},
  language     = {eng},
  number       = {2},
  pages        = {722--729},
  title        = {Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages},
  url          = {http://dx.doi.org/10.1096/fj.11-192112},
  volume       = {26},
  year         = {2012},
}

Chicago
Kleiman, Anna, Sabine Hübner, Jan M Rodriguez Parkitna, Anita Neumann, Stefan Hofer, Markus A Weigand, Michael Bauer, et al. 2012. “Glucocorticoid Receptor Dimerization Is Required for Survival in Septic Shock via Suppression of Interleukin-1 in Macrophages.” Faseb Journal 26 (2): 722–729.
APA
Kleiman, A., Hübner, S., Rodriguez Parkitna, J. M., Neumann, A., Hofer, S., Weigand, M. A., Bauer, M., et al. (2012). Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB JOURNAL, 26(2), 722–729.
Vancouver
1.
Kleiman A, Hübner S, Rodriguez Parkitna JM, Neumann A, Hofer S, Weigand MA, et al. Glucocorticoid receptor dimerization is required for survival in septic shock via suppression of interleukin-1 in macrophages. FASEB JOURNAL. 2012;26(2):722–9.
MLA
Kleiman, Anna, Sabine Hübner, Jan M Rodriguez Parkitna, et al. “Glucocorticoid Receptor Dimerization Is Required for Survival in Septic Shock via Suppression of Interleukin-1 in Macrophages.” FASEB JOURNAL 26.2 (2012): 722–729. Print.